Use of the i2b2 research query tool to conduct a matched case–control clinical research study: advantages, disadvantages and methodological considerations

Background: A major aim of the i2b2 (informatics for integrating biology and the bedside) clinical data informatics framework aims to create an efficient structure within which patients can be identified for clinical and translational research projects. Our objective was to describe the respective roles of the i2b2 research query tool and the electronic medical record (EMR) in conducting a case-controlled clinical study at our institution. Methods: We analyzed the process of using i2b2 and the EMR together to generate a complete research database for a case–control study that sought to examine risk factors for kidney stones among gastrostomy tube (G-tube) fed children. Results: Our final case cohort consisted of 41/177 (23%) of potential cases initially identified by i2b2, who were matched with 80/486 (17%) of potential controls. Cases were 10 times more likely to be excluded for inaccurate coding regarding stones vs. inaccurate coding regarding G-tubes. A majority (67%) of cases were excluded due to not meeting clinical inclusion criteria, whereas a majority of control exclusions (72%) occurred due to inadequate clinical data necessary for study completion. Full dataset assembly required complementary information from i2b2 and the EMR. Conclusions: i2b2 was critical as a query analysis tool for patient identification in our case–control study. Patient identification via procedural coding appeared more accurate compared with diagnosis coding. Completion of our investigation required iterative interplay of i2b2 and the EMR to assemble the study cohort

Proceedings of the Working Group Session on Fertility Preservation for Individuals with Gender and Sex Diversity

Children and adolescents with gender and sex diversity include (1) gender-nonconforming and transgender individuals for whom gender identity or expression are incongruent with birth-assigned sex (heretofore, transgender) and (2) individuals who have differences in sex development (DSD). Although these are largely disparate groups, there is overlap in the medical expertise necessary to care for individuals with both gender and sex diversity. In addition, both groups face potential infertility or sterility as a result of desired medical and surgical therapies. The Ann and Robert H. Lurie Children's Hospital of Chicago (Lurie Children's) gender and sex development program (GSDP) provides specialized multidisciplinary care for both transgender and DSD patients. In response to patient concerns that recommended medical treatments have the potential to affect fertility, the Lurie Children's GSDP team partnered with experts from the Oncofertility Consortium at Northwestern University to expand fertility preservation options to gender and sex diverse youth. This article summarizes the results of a meeting of experts across this field at the annual Oncofertility Consortium conference with thoughts on next steps toward a unified protocol for this patient group.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140296/1/trgh.2016.0008.pd

Differences in gonadal tissue cryopreservation practices for differences of sex development across regions in the United States

ObjectiveSome individuals with differences of sex development (DSD) conditions undergo medically indicated prophylactic gonadectomy. Gonads of individuals with DSD can contain germ cells and precursors and patients interested in future fertility preservation and hormonal restoration can participate in DSD-specific research protocols to cryopreserve this tissue. However, it is unclear how many providers or institutions offer gonadal tissue cryopreservation (GTC) and how widespread GTC for DSD is across the United States (US). The Pediatric Initiative Network (PIN) and Non-Oncologic Conditions committees of the Oncofertility Consortium sought to assess the current state of GTC for patients with DSD.MethodsAn electronic survey was sent to providers caring for patients with DSD via special interest groups of professional societies and research networks.ResultsThe survey was administered between November 15, 2021 and March 14, 2022. A total of 155 providers responded to the survey, of which 132 respondents care for patients with DSD, and 78 work at facilities that offer medically indicated gonadectomy to patients with DSD diagnoses. They represented 55 US institutions including 47 pediatric hospitals, and 5 international sites (Canada, Denmark, Germany, Qatar). Of individual providers, 41% offer cryopreservation after prophylactic gonadectomy for patients with DSD (32/78). At an institutional level, GTC after medically indicated gonadectomy is available at 54.4% (24/46) of institutions. GTC is offered for a variety of DSD diagnoses, most commonly 45,X/46,XY DSD (i.e., Turner Syndrome with Y-chromosome material and mixed gonadal dysgenesis), ovotesticular DSD, complete androgen insensitivity syndrome (CAIS), and complete gonadal dysgenesis. Responses demonstrate regional trends in GTC practices with 83.3% of institutions in the Midwest, 66.7% in the Northeast, 54.6% in the West, and 35.3% in the South providing GTC. All represented institutions (100%) send gonadal tissue for pathological evaluation, and 22.7% preserve tissue for research purposes.ConclusionsGTC after gonadectomy is offered at half of the US institutions represented in our survey, though a minority are currently preserving tissue for research purposes. GTC is offered for several DSD conditions. Future research will focus on examining presence and quality of germ cells to support clinical decision making related to fertility preservation for patients with DSD

Evidence for an association between prostate cancer and chromosome 8q24 and 10q11 genetic variants in African American men: The flint men's health study

Prostate cancer is the most commonly diagnosed non-skin cancer in men in the United States and the second leading cause of cancer-related mortality. African American men have substantially increased risk of both being diagnosed and dying from the disease. Recent genome-wide genetic association studies have identified a number of common single nucleotide genetic polymorphisms (SNPs) that are associated with prostate cancer in men of European descent. Only a small number of studies have evaluated the association between these genetic variants and prostate cancer in African Americans

Comparison of web-based information about cell-free DNA prenatal screening: implications for differences of sex development care

ObjectiveCell-free DNA (cfDNA) prenatal screening is a commercially available noninvasive test that detects fetal genetic material in maternal blood. While expectant parents often use it for “gender” determination, there is little information about unintended consequences of testing, such as revelation of a difference of sex development (DSD). The study aimed to characterize currently available website information about cfDNA and compare the cfDNA-related content.MethodsA systematic search for websites with information about cfDNA was conducted using search terms generated by a natural language processing analysis of the results of an Amazon Mechanical Turk (MTurk) survey of 1,000 parents and then performing a “Google” search, using the terms. Commercial cfDNA testing companies (CC) websites were also identified by consulting a genetic counselor (AGW). Data were collected on about each website’s characteristics and information about cfDNA. Information about cfDNA was compared between websites. Data were analyzed using descriptive statistics, Fisher’s exact test or Kruskal-Wallis test were applied, as appropriate.ResultsSixty websites were identified. After eliminating duplicates, 11 commercial company (CC) websites were identified. Nineteen other websites were reviewed of which six overlapped with five CC websites. Most of the websites had non-professional authors (73.7%), such as laypersons and CC representatives. CC websites were significantly more likely than search term-identified websites to state that cfDNA can screen for trisomy 21 (p=0.002), trisomy 18 (p<0.0001), trisomy 13 (p<0.001), sex chromosome aneuploidies (p<0.001), and microdeletions (p=0.002).ConclusionsThis study shows that most website currently available information for expectant parents about cfDNA prenatal screening is produced by non-professional organizations. There are significant differences between the information provided by CC and Google search websites, specifically about the number of conditions screened for by cfDNA. Improving availability and quality of information about cfDNA could improve counseling future expectant parents. Inclusion of information about the potential for detection of a DSD is needed

Disclosing genetic risk for Alzheimer’s dementia to individuals with mild cognitive impairment

IntroductionThe safety of predicting conversion from mild cognitive impairment (MCI) to Alzheimer’s disease (AD) dementia using apolipoprotein E (APOE) genotyping is unknown.MethodsWe randomized 114 individuals with MCI to receive estimates of 3‐year risk of conversion to AD dementia informed by APOE genotyping (disclosure arm) or not (non‐disclosure arm) in a non‐inferiority clinical trial. Primary outcomes were anxiety and depression scores. Secondary outcomes included other psychological measures.ResultsUpper confidence limits for randomization arm differences were 2.3 on the State Trait Anxiety Index and 0.5 on the Geriatric Depression Scale, below non‐inferiority margins of 3.3 and 1.0. Moreover, mean scores were lower in the disclosure arm than non‐disclosure arm for test‐related positive impact (difference: ‐1.9, indicating more positive feelings) and AD concern (difference: ‐0.3).DiscussionProviding genetic information to individuals with MCI about imminent risk for AD does not increase risks of anxiety or depression and may provide psychological benefits.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154645/1/trc212002_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154645/2/trc212002.pd

Clinical, Pathologic, and Functional Outcomes After Nephron-Sparing Surgery in Patients with a Solitary Kidney: A Multicenter Experience

Abstract Background and Purpose: Surgical management of a renal neoplasm in a solitary kidney is a balance between oncologic control and preservation of renal function. We analyzed patients with a renal mass in a solitary kidney undergoing nephron-sparing procedures to determine perioperative, oncologic, and renal functional outcomes. Patients and Methods: A multicenter study was performed from 12 institutions. All patients with a functional or anatomic solitary kidney who underwent nephron-sparing surgery for one or more renal masses were included. Tumor size, complications, and recurrence rates were recorded. Renal function was assessed with serum creatinine level and estimated glomerular filtration rate. Results: Ninety-eight patients underwent 105 ablations, and 100 patients underwent partial nephrectomy (PN). Preoperative estimated glomerular filtration rate (eGFR) was similar between the groups. Tumors managed with PN were significantly larger than those managed with ablation (P<0.001). Ablations were associated with a lower overall complication rate (9.5% vs 24%, P=0.01) and higher local recurrence rate (6.7% vs 3%, P=0.04). Eighty-four patients had a preoperative eGFR ≥60?mL/min/1.73?m2. Among these patients, 19 (23%) fell below this threshold after 3 months and 15 (18%) at 12 months. Postoperatively, there was no significant difference in eGFR between the groups. Conclusions: Extirpation and ablation are both reasonable options for treatment. Ablation is more minimally invasive, albeit with higher recurrence rates compared with PN. Postoperative renal function is similar in both groups and is not affected by surgical approach.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98449/1/end%2E2012%2E0114.pd

The Impact of Global Warming and Anoxia on Marine Benthic Community Dynamics: an Example from the Toarcian (Early Jurassic)

The Pliensbachian-Toarcian (Early Jurassic) fossil record is an archive of natural data of benthic community response to global warming and marine long-term hypoxia and anoxia. In the early Toarcian mean temperatures increased by the same order of magnitude as that predicted for the near future; laminated, organic-rich, black shales were deposited in many shallow water epicontinental basins; and a biotic crisis occurred in the marine realm, with the extinction of approximately 5% of families and 26% of genera. High-resolution quantitative abundance data of benthic invertebrates were collected from the Cleveland Basin (North Yorkshire, UK), and analysed with multivariate statistical methods to detect how the fauna responded to environmental changes during the early Toarcian. Twelve biofacies were identified. Their changes through time closely resemble the pattern of faunal degradation and recovery observed in modern habitats affected by anoxia. All four successional stages of community structure recorded in modern studies are recognised in the fossil data (i.e. Stage III: climax; II: transitional; I: pioneer; 0: highly disturbed). Two main faunal turnover events occurred: (i) at the onset of anoxia, with the extinction of most benthic species and the survival of a few adapted to thrive in low-oxygen conditions (Stages I to 0) and (ii) in the recovery, when newly evolved species colonized the re-oxygenated soft sediments and the path of recovery did not retrace of pattern of ecological degradation (Stages I to II). The ordination of samples coupled with sedimentological and palaeotemperature proxy data indicate that the onset of anoxia and the extinction horizon coincide with both a rise in temperature and sea level. Our study of how faunal associations co-vary with long and short term sea level and temperature changes has implications for predicting the long-term effects of “dead zones” in modern oceans

Inhibition of Gastric Lipase as a Mechanism for Body Weight and Plasma Lipids Reduction in Zucker Rats Fed a Rosemary Extract Rich in Carnosic Acid

BACKGROUND: Rosemary (Rosmarinus officinalis L.) extracts (REs) exhibit hepatoprotective, anti-obesity and anti-inflammatory properties and are widely used in the food industry. REs are rich in carnosic acid (CA) and carnosol which may be responsible for some of the biological activities of REs. The aim of this study was to investigate whether inhibition of lipase activity in the gut may be a mechanism by which a RE enriched in CA (40%) modulates body weight and lipids levels in a rat model of metabolic disorders and obesity. METHODS AND PRINCIPAL FINDINGS: RE was administered for 64 days to lean (fa/+) and obese (fa/fa) female Zucker rats and body weight, food intake, feces weight and blood biochemical parameters were monitored throughout the study. Lipase activity (hydrolysis of p-nitrophenylbutyrate) was measured in the gastrointestinal tract at the end of the study and the contents of CA, carnosol and methyl carnosate were also determined. Sub-chronic administration of RE moderately reduced body weight gain in both lean and obese animals but did not affect food intake. Serum triglycerides, cholesterol and insulin levels were also markedly decreased in the lean animals supplemented with RE. Importantly, lipase activity was significantly inhibited in the stomach of the RE-supplemented animals where the highest content of intact CA and carnosol was detected. CONCLUSIONS: Our results confirm that long-term administration of RE enriched in CA moderates weight gain and improves the plasma lipids profile, primarily in the lean animals. Our data also suggest that these effects may be caused, at least in part, by a significant inhibition of gastric lipase and subsequent reduction in fat absorption