Participation In Clinical Studies Research Articles

A multi-center study on the use of lidocaine thermogel for pain control in outpatient operative hysteroscopy

ObjectivesThis study aimed to explore the use of an anesthetic lidocaine thermogel in outpatient operative hysteroscopies. Specifically, it assessed the safety, tolerability, and ease of use of the gel, as well as its potential for pain reduction during the procedure. Study designThis was a multicenter observational study conducted in 9 gynecological units between March 2023 and January 2024. The study included adult women scheduled for outpatient operative hysteroscopies, excluding those with hypersensitivity to the product or recent participation in other clinical studies. The target sample size was 60 to account for potential dropouts. Data collection was electronic, and SPSS was used for analysis. The study assessed visibility conditions, procedure duration, pain scores at different stages of the procedure, and adverse event frequency. Statistical analyses utilized descriptive statistics, Student’s t-tests, Wilcoxon and Friedman tests, and Chi-Square or Fisher tests as appropriate. Binary logistic regression was applied to identify factors influencing gel volume. ResultsAll 60 participants met the inclusion criteria. The mean age was 45.5 (SD 8.8) years, with a mean BMI of 27.0 (SD 5.6) kg/m2. Medical histories were reported in 46.7% of participants, and 50% had undergone previous gynecological surgeries. Prior to the procedure, 51.8% of participants took analgesics. The average procedure duration was 13.9 (SD 15.1) minutes. Pain scores were collected at different stages of the procedure, with median VAS scores ranging from 0 to 5 out of 10. In 50% of cases, the quality of vision during the procedure was rated 9 or higher on a 10-point scale. The full recommended dose of thermogel was administered in 91.7% of cases. The mean gel volume used was 7.0 (SD 1.9) milliliters. Regression analysis showed that younger age and a history of abortions or childbirth were significantly associated with higher gel volume use. ConclusionsThe anesthetic thermogel demonstrated effectiveness in managing pain during outpatient operative hysteroscopies, with median pain scores ranging from 0 to 5 out of 10 across different stages of the procedure. The gel showed a favorable safety profile, with only 15% of participants reporting adverse effects, all of which were minor and resolved satisfactorily. The high rate of complete gel application (91.7% of cases) and positive physician feedback suggest good tolerability and ease of use. Further research is recommended to evaluate the gel’s efficacy in other gynecological procedures and to optimize application protocols based on patient-specific factors such as age and reproductive history.

Clindamycin Phosphate 1.2%/Adapalene 0.15%/Benzoyl Peroxide 3.1% Gel in Participants With Moderate-to-Severe Acne: The Patient Journey.

Topical clindamycin phosphate 1.2%/adapalene 0.15%/benzoyl peroxide 3.1% (CAB) gel is the only fixed-dose, triple-combination formulation approved for acne treatment. In 3 clinical studies of participants with moderate-to-severe acne, CAB demonstrated superior efficacy to vehicle and component dyads, with good safety and tolerability. Detailed efficacy/safety data from individual clinical study participants are presented. In two phase 3 (NCT04214652, NCT04214639) randomized, double-blind, 12-week studies, participants aged at least 9 years with moderate-to-severe acne were randomized to once-daily CAB or vehicle gel. Descriptive data - including lesion count changes, treatment success (at least 2-grade reduction from baseline in Evaluator's Global Severity Score and clear/almost clear skin), compliance, treatment-emergent adverse events (AEs), and cutaneous safety/tolerance assessments - were summarized from 6 CAB-treated cases. By week 12, all cases achieved >70% lesion reductions, 4/6 achieved treatment success, and 1/6 achieved a 2-grade reduction in severity. All cases were compliant with CAB treatment. No cases reported serious AEs. Transient increases occurred on cutaneous safety and tolerability assessments, with scores generally decreasing back to/below baseline levels by week 12. In two phase 3 clinical trials, fixed-dose, triple-combination CAB demonstrated good efficacy/safety. All 6 CAB-treated cases achieved substantial (>70%) lesion reductions, with 5/6 achieving treatment success or 2-grade reduction in severity by week 12. Transient cutaneous safety/tolerability severity increases generally resolved to baseline values by week 12. These clinical study cases reinforce the importance of patient education regarding adherence, expectations, and AEs. J Drugs Dermatol. 2024;23(11):1017-1024. doi:10.36849/JDD.8639.

Abstract B120: Understanding Barriers and Facilitators Affecting Participation in Cancer Clinical Research Studies for Racially and Ethnically Diverse Populations in Rural North Carolina

Abstract Increasing representation of minoritized racial and ethnic populations in cancer clinical research studies has been declared a priority in the US for many years. Additionally, it is widely recognized that people living in rural areas of the US have limited access to cancer clinical research studies, and solutions are needed to extend participation opportunities to rural cancer patients. Underrepresentation of minoritized racial and ethnic populations and rural communities perpetuates health inequities, and solutions are needed to remove barriers and implement facilitators for participation. However, a review of existing literature found a lack of attention on the intersection of race and rurality and the needs and values of these populations as it pertains to cancer research. To address this concern, we used a sequential mixed method, community-engaged approach to explore the barriers and facilitators affecting participation in cancer clinical research from the perspectives of cancer survivors and their caregivers, as well as cancer healthcare professionals in rural North Carolina (NC). We used existing publicly available data to identify and characterize four of the most rural, racially and ethnically diverse, and medically underserved counties in NC. The principal investigator collaborated with cancer centers, churches, and American Indian tribal leaders in NC to administer surveys to cancer survivors and caregivers to assess their beliefs and experiences regarding cancer clinical research. Eligible participants included persons who had been diagnosed with cancer or a caregiver of someone diagnosed with cancer. In addition, we conducted key informant interviews with cancer health care professionals providing cancer care in the selected rural NC counties. We analyzed surveys and interview responses with descriptive statistics. Forty-three cancer survivors/caregivers completed surveys and twenty-two cancer healthcare professionals completed semi-structured interviews. Cancer survivors and caregivers indicated that the lack of invitation to participate in cancer clinical research was their greatest barrier to participation, whereas cancer healthcare professionals cited the lack of transportation as the perceived greatest barrier for patients. Cancer survivors, caregivers and healthcare professionals agreed that having support from clinical research personnel would be amongst the most helpful facilitators, along with opportunities to participate in clinical research studies close to home. Cancer healthcare professionals suggested the lack of trust in clinical research was a barrier for their patients; however, cancer survivors and caregivers in this study indicated lack of trust was not a significant barrier to their participation. Recommendations to address barriers and promote facilitators to participation in cancer clinical research include the importance of engaging the community, addressing unconscious bias, decentralizing clinical trials, and providing recruitment materials in culturally responsive formats. Citation Format: Amy Garrett, Karine Dubé, Lisa Spees, Ronny Bell, Marjory Charlot, Sandra Greene. Understanding Barriers and Facilitators Affecting Participation in Cancer Clinical Research Studies for Racially and Ethnically Diverse Populations in Rural North Carolina [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr B120.

The impact of sex on HIV immunopathogenesis and therapeutic interventions.

Globally, the majority of people living with HIV are women or girls, but they have been a minority of participants in clinical trials and observational studies of HIV. Despite this underrepresentation, differences in the pathogenesis of HIV have been observed between men and women, with contributions from both gender- and sex-based factors. These include differences in the risk of HIV acquisition, in viral load set point and immune activation in responses to viremia, and differences in HIV reservoir maintenance. These differences obligate adequate study in both males and females in order to optimize treatments, but also provide a powerful leverage point for delineating the mechanisms of HIV pathogenesis. The shifts in exposure to sex steroid hormones across a lifespan introduce additional complexity, which again can be used to focus on either genetic or hormonal influences as the driver of an outcome. In this Review, we discuss consistent and reproducible differences by sex across the spectrum of HIV, from acquisition through pathogenesis, treatment, and cure, and explore potential mechanisms and gaps in knowledge.

Assessment of antibodies against platelet factor 4 following vaccination with adenovirus type 26–vectored vaccines

BackgroundVaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare adverse event identified following vaccination with some adenovirus-vectored COVID-19 vaccines, including Ad26.COV2.S. VITT is characterized by the presence of antibodies against platelet factor 4 (PF4). ObjectivesTo evaluate whether PF4 antibodies were generally induced following vaccination with adenovirus type 26 (Ad26)–vectored vaccines. MethodsThe study included 913 and 991 healthy participants without thromboembolic (TE) events in Ad26.COV2.S and non–COVID-19 Ad26-vectored vaccine clinical studies, respectively, and 1 participant with VITT following Ad26.COV2.S vaccination. PF4 antibody levels were measured in prevaccination and postvaccination sera. PF4 antibody positivity rates were assessed in a case-control setting in participants who developed TE events during participation in Ad26-vectored vaccine clinical studies. ResultsIn the 1 VITT patient, PF4 antibodies were negative before vaccination. Seroconversion for platelet-activating PF4 antibodies was observed upon Ad26.COV2.S vaccination. In participants without TE events, the PF4 antibody levels and positivity rates were similar before and after Ad26 vaccination. Ad26 vaccination did not increase PF4 antibody levels in participants who were PF4 antibody–positive at baseline (n = 47). Lastly, 1 out of 28 TE cases and 2 out of 156 non-TE controls seroconverted after Ad26.COV2.S vaccination. None of the 15 TE cases and 3 of the 77 non-TE controls seroconverted following non–COVID-19 Ad26 vaccination. ConclusionAd26.COV2.S and the other Ad26-vectored vaccines studied did not generally induce PF4 antibodies or increase preexisting PF4 antibody levels. Moreover, unlike VITT, TE events that occurred at any time following Ad26 vaccination were not associated with PF4 antibodies.

Management of acute uncomplicated diverticulitis and adherence to current guidelines-a multicentre SNAPSHOT study.

To explore whether previous participation in clinical studies increases adherence to management guidelines in acute uncomplicated diverticulitis (AUD). This retrospective cohort study was designed to give a SNAPSHOT of the management of AUD at six hospitals, three of which had participated in the AVOD trial comparing antibiotic versus non-antibiotic treatment of AUD. Patients with AUD were included from March 2019 through June 2020 and followed for 90days. The primary outcome was treatment of AUD categorised by antibiotic treatment and inpatient or outpatient management compared between AVOD and non-AVOD hospitals. Descriptive statistics were compiled, and differences between hospitals were assessed with Pearson's chi-squared test. The cohort included 449 patients with AUD of which 63% were women and the median age was 63 (IQR: 52-73) years. Patient characteristics were comparable across the hospitals. Antibiotics were administered to 84 (19%) patients and 113 (25%) patients were managed as inpatients. Management varied significantly between AVOD and non-AVOD hospitals. The mean proportion of patients treated with antibiotics was 7% at AVOD hospitals compared to 38% at non-AVOD hospitals (p < 0.001). The mean proportion of in-hospital management was 18% at AVOD hospitals versus 38% at non-AVOD hospitals (p < 0.001). Most patients with AUD were managed according to current guidelines. However, the management varies between hospitals and previous participation in clinical studies may increase knowledge of and adherence to guidelines.

The Answer ALS return of results study: Answering the duty to disclose

Objective: The Return of Answer ALS Results (RoAR) Study was designed to provide a mechanism for participants in Answer ALS, a large, prospectively designed natural history and biorepository study to receive select clinical genetic testing results and study participants’ experience with the results disclosure. Methods: Participants consented to receive results of five ALS genes (C9orf72, SOD1, FUS, TARDP, TBK1) and/or 59 medically actionable genes as designated by the American College of Medical Genetics. Patient-reported genetic testing outcomes were measured via a post-disclosure survey. Results: Of 645 eligible Answer ALS enrollees, 143 (22%) enrolled and completed participation in RoAR. Pathogenic variants were identified in 22/143 (15.4%) participants, including 13/143 (9.0%) in ALS genes and 9/143 (6.3%) in ACMG genes. Participant-reported measures of result utility indicated the research result disclosure was as or more successful than published patient-reported outcomes of result disclosure the clinical setting. Conclusions: This study serves as a model of a “disclosure study” to share results from genomic research with participants who were not initially offered the option to receive results, and our findings can inform the design of future, large scale genomic projects to empower research participants to access their genetic information.

Derivatization-free determination of chiral plasma pharmacokinetics of MDMA and its enantiomers

3,4-Methylenedioxymethamphetamine (MDMA) is an entactogen with therapeutic potential. The two enantiomers of MDMA differ regarding their pharmacokinetics and pharmacodynamics but the chiral pharmacology of MDMA needs further study in clinical trials. Here, an achiral and an enantioselective high performance liquid chromatography–tandem mass spectrometry method for the quantification of MDMA and its psychoactive phase I metabolite 3,4-methylenedioxyamphetamine (MDA) in human plasma were developed and validated. The analytes were detected by positive electrospray ionization followed by multiple reaction monitoring. The calibration range was 0.5–500 ng/mL for the achiral analysis of both analytes, 0.5–1,000 ng/mL for chiral MDMA analysis, and 1–1,000 ng/mL for chiral MDA analysis. Accuracy, precision, selectivity, and sensitivity of both bioanalytical methods were in accordance with regulatory guidelines. Furthermore, accuracy and precision of the enantioselective method were maintained when racemic calibrations were used to measure quality control samples containing only one of the enantiomers. Likewise, enantiomeric calibrations could be used to reliably quantify enantiomers in racemic samples. The achiral and enantioselective methods were employed to assess pharmacokinetic parameters in clinical study participants treated with racemic MDMA or one of its enantiomers. The pharmacokinetic parameters assessed with both bioanalytical methods were comparable. In conclusion, the enantioselective method is useful for the simultaneous quantification of both enantiomers in subjects treated with racemic MDMA. However, as MDMA and MDA do not undergo chiral inversion, enantioselective separation is not necessary in subjects treated with only one of the enantiomers.

Lessons Learned From Clinical Studies in Centronuclear Myopathies: The Patient Perspective—A Qualitative Study

BackgroundSince 2014, several clinical studies focusing on centronuclear myopathies have been conducted, including a prospective natural history study, a gene transfer clinical trial and a clinical trial using an antisense oligonucleotide. Dedicated patient organizations have played an important role in this process. The experience of members of these organizations, either as a study participant, parent or as a patient organization member communicating with the sponsors are potentially very informative for future trial design. MethodsWe investigated the burden of and the lessons learned from the first natural history studies and clinical trials from a patient perspective using a qualitative approach. We arranged 4 focus groups with a total of 37 participants from 3 large international patient organizations: ZNM-ZusammenStark!, the Myotubular Trust, and the MTM-CNM Family Connection. 4 themes, based on a systematic literature search were discussed: Expectations and preparation, Clinical study participation, Communication and Recommendations for future clinical trials. The focus group recordings were transcribed, anonymized, and uploaded to Atlas-ti version 8.1 software. The data were analyzed using a thematic content analysis. ResultsOverall, participants were realistic in their expectations, hoping for small improvements of function and quality of life. The realization that trial participation does not equate to a treatment was challenging. Participating in a clinical study had a huge impact on many aspects of daily life, both for patients and their immediate families. First-hand insights into the burden of the design and its possible effect on performance were provided, resulting in numerous compelling recommendations for future clinical studies. Furthermore, participants stressed the importance of clear communication, which was considered to be especially vital in cases of severe adverse events. Finally, while patients were understanding of the importance of adhering to the regulations of good clinical practice, they indicated that they would strongly appreciate a greater understanding and/or acknowledgment of the patient perspective and a reflection of this perspective in future clinical trial design. ConclusionThe acknowledgment and inclusion of patients’ perspectives and efficient and effective communication is expected to improve patient recruitment and retention in future clinical studies, as well as more accurate assessment of the patient performance related to suitable planning of the study visits.

Parental perspectives on pediatric inflammatory bowel disease: Unraveling concerns, and study participation willingness.

The impact of disease burden extends beyond pediatric inflammatory bowel disease (IBD) patients to include their parents. Previous studies, predating the biologic era, have highlighted parental concerns about potential side effects associated with IBD medications. However, there is a notable gap in the literature regarding parents' perceptions of clinical studies involving pediatric IBD patients. This study aims to explore the specific concerns troubling parents of children with IBD, identifying factors influencing these concerns, and assesses parental willingness to allow their child's participation in clinical studies. Utilizing social media, we disseminated an anonymous questionnaire to parents of pediatric IBD patients. The questionnaire encompassed queries about parental willingness for their child to partake in clinical studies, aspects of the disease deemed bothersome, and the sense of coherence scale (SOC). Responses were obtained from 101 parents, with a mean age of 46.4, of whom 82.2% were female. Concerns about potential future side effects of their child's medications surpassed worries about disease symptoms (80.04% vs. 73.47%). Linear regression analysis revealed that parents with lower SOC scores, limited medical care accessibility, and a higher age of the child at diagnosis, exhibited heightened concerns about the future impact of the disease on their child (p = 0.016, 0.003, and 0.045, respectively). While a majority rejected participation in studies involving new medications (54.5%), there was greater agreement for studies on nutritional therapies (84.2%) and complementary medicine (91.1%). Classification tree analysis indicated that women were more inclined to permit their child's participation in studies focusing on complementary medicine (adjusted p = 0.002). Parents of IBD patients express greater apprehension about potential side effects from IBD medications and display reluctance toward their child participating in clinical studies related to medications.

Identification of Persons Living with Dementia Using the Electronic Health Record

AbstractBackgroundAlzheimer’s disease and related dementias (ADRD) are underdiagnosed in the primary care setting. Proactive screening for cognitive impairment and subsequent evaluation and diagnosis of patients who screen positive are not routinely and reliably performed. As a result, identification of persons living with dementia (PLWD) for enrollment in clinical programs, clinical trials, and research studies can be challenging. The electronic health record (EHR) represents a potentially viable tool to efficiently and accurate identify PLWD.MethodsIn a large academic health care system in the U.S., we performed an EPIC EHR search for PLWD with the intent of enrolling them in an outpatient dementia care management program. The EHR algorithm used the following criteria for dementia: (1) an ICD‐10 dementia diagnosis in the problem list or past medical history or (2) an FDA‐approved drug on their active medication list. We performed chart review for patients who were identified to have potential dementia using this algorithm to confirm dementia diagnosis is documented in clinical notes.ResultsA total of 985 patients were identified by EHR criteria as potentially having dementia. After chart review, 747 (75.8%) were confirmed to have dementia documented in their clinical history and progress notes. One hundred thirty (13.2%) did not have a confirmed dementia diagnosis, 58 (5.9%) had an incomplete dementia evaluation, and 50 (5.0%) had only mild cognitive impairment. In addition, 55 (5.6%) were deceased.ConclusionWe found that an EHR algorithm can identify patients with dementia in a health plan population. This model may be a useful tool for a focused recruitment of potential participants in clinical trials, research studies, and clinical programs.

Post-Marketing Observational Study of the Safety and Efficacy of Fibrinogen Concentrate in Congenital Fibrinogen Deficiency in Patients of All Ages

Background and Significance: Congenital fibrinogen deficiency (CFD) is a rare coagulation disorder characterized by a lack or low levels of functional fibrinogen leading to inadequate clot formation. Patients with CFD may experience severe or frequent bleeding episodes (BEs), either spontaneously or following trauma or surgery. Human fibrinogen concentrate (HFC; Fibryga® [Octapharma]) can restore hemostasis, and its efficacy and safety has been demonstrated in interventional clinical studies of adult and pediatric patients. The primary objective of this planned observational study is to collect real-world evidence to further assess the safety profile of this HFC, in patients of all ages with congenital fibrinogen deficiency, by characterizing the risks of thrombosis and anaphylaxis following its administration for treatment of bleeding (Figure 1). The observational data collected in this study will provide a more comprehensive safety profile of this HFC in patients of all ages following its marketing authorization. Study Design and Methods: FORMA-07 (NCT03793426) is a prospective, non-interventional, multicenter, observational, post-marketing study. Patients of all ages with a documented diagnosis of CFD (i.e., congenital afibrinogenemia or hypofibrinogenemia) requiring on demand HFC for BE treatment are eligible for inclusion (Table 1). Exclusion criteria include other coagulation disorders, history of anti-fibrinogen inhibitors, and participation in concurrent clinical studies. This study will examine a highly purified, plasma derived, double virus inactivated/eliminated, lyophilized HFC, which will be used according to individual country approval and labelling, and individually dosed as per the locally approved package insert. Independent ethical committee approval will be sought prior to study start and freely given, written informed consent obtained from all participants, or legal guardians in the case of pediatric patients. This study will be conducted in accordance with the ethical principles laid down in the Declaration of Helsinki. The primary endpoint is the incidence of thromboembolic adverse drug reactions (ADRs) . Serious ADRs, ADRs of special interest (including thromboembolic events and anaphylaxis), and thromboembolic monitoring using the Wells Score will be documented. Hemostatic efficacy will be assessed as a secondary endpoint by the study investigator using a robust 4-point objective scale from 2 to 24 hours following treatment. FORMA-07 is ongoing and actively enrolling patients of all ages with CFD. The study aims to enroll ~25 patients over 7 years, collecting data from 105 BEs (≥10 major BEs in 10 patients). Results of HFC safety and efficacy will be continually monitored throughout the study. Completion is expected Q4 2027.

Examining Racial Disparities in Multiple Myeloma Research and Treatment

Multiple myeloma (MM) is a disease which occurs in all races, geographic locations, and ethnicities, however the burden of this cancer is especially prominent in the African American/Black population with prevalence estimated to be as high as two to three times that of the White population. As a result MM is the most common hematological malignancy in Black patients. Despite a higher disease burden, this population suffers disproportionate rates of mortality. From 2017-2022 Black men had a 6% higher incidence rate than White men, but a 19% higher mortality rate. This disparity in outcomes between ethnic groups is likely multifactorial. Some explanations include novel therapy underutilization, or prevalence of comorbid conditions. It may also be attributable to biological differences, such as an increase rate of immunoglobin A disease, and an increased rate of chromosome 14 translocations. There may as a result be a heterogenous response to novel MM therapy. Unfortunately, clinical trial participation of Black patients has been significantly underrepresented. Studies that sought to analyze the results of novel therapy trials in this population found a trend towards decreased efficacy, however, were unable to reach significance due to insufficient study participation. We conducted a pooled analysis of interventional phase III clinical trials obtained from ClinicalTrials.gov data from 01/01/2000 to 12/31/2022. Studies who did not include racial/ethnicity data were excluded. There were 34 trials included in total that met this criteria and included in this analysis. There were 16,405 total enrolled patients analyzed. 13,618 (83.01%) were White, 1,255 (9.21%) were Asian, 777 (4.74%) were Black/African American, and 454 (2.7%) identified as Hispanic, with the remaining identified as other. Study participation was analyzed over time. Percentage of patients enrolled by year showed a negative correlation in Black/African Americans over the analyzed period. Our analysis suggests greater efforts need to be made to ensure the enrollment of a more diverse and representative MM population. Although this disease is roughly twice as prevalent in Black populations, clinical trial study participation since 2003 involved 18-times more White than Black patients. Despite ongoing recognition of this problem, study participation in MM has continued to remain largely homogenous. Interventions that may improve this problem include fostering and rebuilding trust in the clinical trial system that was damaged from historical abuses, expanding clinical sites to more diverse areas, expanding/revising eligibility criteria, and employing changes to enrollment techniques that better represent the demographics of the population intended to treat. Ultimately, the clinical trials for an intervention should appropriately reflect the population who will use it, otherwise these novel treatments may have unexpected heterogeneity in efficacy and safety once employed clinically.

Mexican Americans agree to participate in longitudinal clinical research more than non-Hispanic whites

BackgroundThe National Institutes of Health has advocated for improved minority participation in clinical research, including clinical trials and observational epidemiologic studies since 1993. An understanding of Mexican Americans (MAs) participation in clinical research is important for tailoring recruitment strategies and enrollment techniques for MAs. However, contemporary data on MA participation in observational clinical stroke studies are rare. We examined differences between Mexican Americans (MAs) and non-Hispanic whites (NHWs) participation in a population-based stroke study.MethodsWe included 3,594 first ever stroke patients (57.7% MAs, 48.7% women, median [IQR] age 68 [58–79]) from the Brain Attack Surveillance in Corpus Christi Project, 2009–2020 in Texas, USA, who were approached and invited to participate in a structured baseline interview. We defined participation as completing a baseline interview by patient or proxy. We used log-binomial models adjusting for prespecified potential confounders to estimate prevalence ratios (PR) of participation comparing MAs with NHWs. We tested interactions of ethnicity with age or sex to examine potential effect modification in the ethnic differences in participation. We also included an interaction between year and ethnicity to examine ethnic-specific temporal trends in participation.ResultsBaseline participation was 77.0% in MAs and 64.2% in NHWs (Prevalence Ratio [PR] 1.20; 95% CI, 1.14–1.25). The ethnic difference remained after multivariable adjustment (1.17; 1.12–1.23), with no evidence of significant effect modification by age or sex (Pinteraction by age = 0.68, Pinteraction by sex = 0.83). Participation increased over time for both ethnic groups (Ptrend < 0.0001), but the differences in participation between MAs and NHWs remained significantly different throughout the 11-year time period.ConclusionMAs were persistently more likely to participate in a population-based stroke study in a predominantly MA community despite limited outreach efforts towards MAs during study enrollment. This finding holds hope for future research studies to be inclusive of the MA population.

Operation Diversify Plastic Surgery: An Innovative Strategy to Increase Diversity in Plastic and Reconstructive Surgery.

Healthcare disparities remain a significant problem facing the US healthcare system with recent evidence of persistent racial and ethnic disparities especially among patients from minority backgrounds. Recent studies have documented advantages to a racially and ethnically diverse surgical workforce such as higher patient satisfaction scores, superior patient compliance with physician recommendations, and increased participation in clinical research studies by minority patients. In plastic and reconstructive surgery (PRS), there is a noted deficit among residents and faculty that come from ethnically underrepresented in medicine (URiM) backgrounds despite recent efforts to increase diversity in PRS surgeons. URiM medical students from three of the four historically Black medical universities organized to discuss pathways to PRS. Operation Diversify Plastic Surgery is a student-led organization that was developed to address the lack of diversity in PRS, challenges faced by students from institutions that lack PRS residency training programs, and unique factors that affect URiM students interested in PRS. Available studies note that mentoring relationships and research opportunities were instrumental in recruiting URiM students into PRS residency programs. Operation Diversify Plastic Surgery is an innovative solution to the insufficient URiM PRS residency candidate pool by increasing medical student exposure to PRS via educational lectures, virtual mentoring opportunities, and insights into research fellowships.

Screening and validation of differentially expressed genes in adipose tissue of patients with obesity and type 2 diabetes mellitus.

White adipose tissue (WAT) plays a pivotal role in the onset of type 2 diabetes mellitus (T2DM) and obesity. Despite its significance the underlying pathogenesis and key genes associated with it remain elusive. In our study, we screened the differentially expressed genes (DEGs) in intra-abdominal WAT of T2DM patients with obesity, as well as those with simple obesity, aiming to lay a foundational theory for an in-depth investigation of T2DM pathogenesis and the identification of novel therapeutic targets. Gene expression datasets (GSE16415 and GSE71416) were retrieved from the Gene Expression Omnibus (GEO) database. We employed R for screening DEGs and conducted a functional enrichment analysis using the Metascape database. Combined Lasso regression and Boruta feature selection algorithms were used to identify key DEGs. Subsequently, these were cross-verified using the GSE29231 dataset. Samples and medical records were collected from clinical study participants. The mRNA and protein expressions of the key DEGs were verified using qRT-PCR and western blotting, respectively. We discerned a total of 130 DEGs, with 40 being upregulated and 90 downregulated. Functional and pathway enrichment analyses illuminated that these genes are instrumental in mediating metabolite and energy production, neutrophil-mediated immunity, and other associated biological processes. This includes their involvement in the tricarboxylic acid cycle, glycolysis/gluconeogenesis, peroxisome proliferator-activated receptors, and other signalling pathways. Two genes, CIDEA and FSCN1 emerged as key DEGs. The low expression of CIDEA and high expression of FSCN1 in the T2DM and obesity group were verified in clinical samples (P < 0.05). We established that CIDEA and FSCN1 manifest significant differential expression in T2DM patients who are obese. This suggests their potential as risk assessment markers and therapeutic targets for T2DM.

A high-throughput test enables specific detection of hepatocellular carcinoma

High-throughput tests for early cancer detection can revolutionize public health and reduce cancer morbidity and mortality. Here we show a DNA methylation signature for hepatocellular carcinoma (HCC) detection in liquid biopsies, distinct from normal tissues and blood profiles. We developed a classifier using four CpG sites, validated in TCGA HCC data. A single F12 gene CpG site effectively differentiates HCC samples from other blood samples, normal tissues, and non-HCC tumors in TCGA and GEO data repositories. The markers were validated in a separate plasma sample dataset from HCC patients and controls. We designed a high-throughput assay using next-generation sequencing and multiplexing techniques, analyzing plasma samples from 554 clinical study participants, including HCC patients, non-HCC cancers, chronic hepatitis B, and healthy controls. HCC detection sensitivity was 84.5% at 95% specificity and 0.94 AUC. Implementing this assay for high-risk individuals could significantly decrease HCC morbidity and mortality.

Unsupervised [18F]Flortaucipir cutoffs for tau positivity and staging in Alzheimer’s disease

PurposeSeveral [18F]Flortaucipir cutoffs have been proposed for tau PET positivity (T+) in Alzheimer’s disease (AD), but none were data-driven. The aim of this study was to establish and validate unsupervised T+ cutoffs by applying Gaussian mixture models (GMM).MethodsAmyloid negative (A−) cognitively normal (CN) and amyloid positive (A+) AD-related dementia (ADRD) subjects from ADNI (n=269) were included. ADNI (n=475) and Geneva Memory Clinic (GMC) cohorts (n=98) were used for validation. GMM-based cutoffs were extracted for the temporal meta-ROI, and validated against previously published cutoffs and visual rating.ResultsGMM-based cutoffs classified less subjects as T+, mainly in the A− CN (<3.4% vs >28.5%) and A+ CN (<14.5% vs >42.9%) groups and showed higher agreement with visual rating (ICC=0.91 vs ICC<0.62) than published cutoffs.ConclusionWe provided reliable data-driven [18F]Flortaucipir cutoffs for in vivo T+ detection in AD. These cutoffs might be useful to select participants in clinical and research studies.

Representative enrolment of older adults in clinical trials: the time is now

Representative enrolment of older adults in clinical trials: the time is now

The MPRINT Hub Data, Model, Knowledge and Research Coordination Center: Bridging the gap in maternal-pediatric therapeutics research through data integration and pharmacometrics.

Maternal and pediatric populations have historically been considered "therapeutic orphans" due to their limited inclusion in clinical trials. Physiologic changes during pregnancy and lactation and growth and maturation of children alter pharmacokinetics (PK) and pharmacodynamics (PD) of drugs. Precision therapy in these populations requires knowledge of these effects. Efforts to enhance maternal and pediatric participation in clinical studies have increased over the past few decades. However, studies supporting precision therapeutics in these populations are often small and, in isolation, may have limited impact. Integration of data from various studies, for example through physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) modeling or bioinformatics approaches, can augment the value of data from these studies, and help identify gaps in understanding. To catalyze research in maternal and pediatric precision therapeutics, the Obstetric and Pediatric Pharmacology and Therapeutics Branch of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) established the Maternal and Pediatric Precision in Therapeutics (MPRINT) Hub. Herein, we provide an overview of the status of maternal-pediatric therapeutics research and introduce the Indiana University-Ohio State University MPRINT Hub Data, Model, Knowledge and Research Coordination Center (DMKRCC), which aims to facilitate research in maternal and pediatric precision therapeutics through the integration and assessment of existing knowledge, supporting pharmacometrics and clinical trials design, development of new real-world evidence resources, educational initiatives, and building collaborations among public and private partners, including other NICHD-funded networks. By fostering use of existing data and resources, the DMKRCC will identify critical gaps in knowledge and support efforts to overcome these gaps to enhance maternal-pediatric precision therapeutics.