To describe the parental experience of recruitment and assess differences between parents who participated and those who declined to enroll in a neonatal clinical trial.
This was a survey conducted ...at 12 US neonatal intensive care units of parents of infants who enrolled in the High-dose Erythropoietin for Asphyxia and encephaLopathy (HEAL) trial or who were eligible but declined enrollment. Questions assessed 6 factors of the parental experience of recruitment: (1) interactions with research staff; (2) the consent experience; (3) perceptions of the study; (4) decisional conflict; (5) reasons for/against participation; and (6) timing of making the enrollment decision.
In total, 269 of 387 eligible parents, including 183 of 242 (75.6%) of those who enrolled their children in HEAL and 86 of 145 (59.3%) parents who declined to enroll their children in HEAL, were included in analysis. Parents who declined to enroll more preferred to be approached by clinical team members rather than by research team members (72.9% vs 49.2%, P = .005). Enrolled parents more frequently reported positive initial impressions (54.9% vs 10.5%, P < .001). Many parents in both groups made their decision early in the recruitment process. Considerations of reasons for/against participation differed by enrollment status.
Understanding how parents experience recruitment, and how this differs by enrollment status, may help researchers improve recruitment processes for families and increase enrollment. The parental experience of recruitment varied by enrollment status. These findings can guide future work aiming to inform optimal recruitment strategies for neonatal clinical trials.
Epidermolysis bullosa (EB) is characterized by blistering of the skin and mucosal erosions caused by hemidesmosomal abnormalities. EB is divided into 3 major subgroups depending on the particular ...location of tissue separation: EB simplex, dystrophic EB, and junctional EB. Junctional EB (JEB) can further be broken down into Herlitz, non-Herlitz, and JEB with pyloric atresia (Carmi syndrome) depending on genetic and histologic testing. When extensive, management of a patient with EB can be challenging due to not only cutaneous but also extracutaneous manifestations as well. Families and health care teams are often faced with difficult decisions in their infant’s best interest. We report a case of a preterm neonate with Carmi syndrome and unique findings on immunofluorescence studies. The patient’s course was complicated by multisystem involvement and ultimately death. A multidisciplinary approach was crucial in the light of diagnostic, therapeutic, and ethical challenges.
IMPORTANCE: It remains poorly understood how parents decide whether to enroll a child in a neonatal clinical trial. This is particularly true for parents from racial or ethnic minority populations. ...Understanding factors associated with enrollment decisions may improve recruitment processes for families, increase enrollment rates, and decrease disparities in research participation. OBJECTIVE: To assess differences in parental factors between parents who enrolled their infant and those who declined enrollment for a neonatal randomized clinical trial. DESIGN, SETTING, AND PARTICIPANTS: This survey study conducted from July 2017 to October 2019 in 12 US level 3 and 4 neonatal intensive care units included parents of infants who enrolled in the High-dose Erythropoietin for Asphyxia and Encephalopathy (HEAL) trial or who were eligible but declined enrollment. Data were analyzed October 2019 through July 2020. EXPOSURE: Parental choice of enrollment in neonatal clinical trial. MAIN OUTCOMES AND MEASURES: Percentages and odds ratios (ORs) of parent participation as categorized by demographic characteristics, self-assessment of child’s medical condition, study comprehension, and trust in medical researchers. Survey questions were based on the hypothesis that parents who enrolled their infant in HEAL differ from those who declined enrollment across 4 categories: (1) infant characteristics and parental demographic characteristics, (2) perception of infant’s illness, (3) study comprehension, and (4) trust in clinicians and researchers. RESULTS: Of a total 387 eligible parents, 269 (69.5%) completed the survey and were included in analysis. This included 183 of 242 (75.6%) of HEAL-enrolled and 86 of 145 (59.3%) of HEAL-declined parents. Parents who enrolled their infant had lower rates of Medicaid participation (74 41.1% vs 47 55.3%; P = .04) and higher rates of annual income greater than $55 000 (94 52.8% vs 30 37.5%; P = .03) compared with those who declined. Black parents had lower enrollment rates compared with White parents (OR, 0.35; 95% CI, 0.17-0.73). Parents who reported their infant’s medical condition as more serious had higher enrollment rates (OR, 5.7; 95% CI, 2.0-16.3). Parents who enrolled their infant reported higher trust in medical researchers compared with parents who declined (mean SD difference, 5.3 0.3-10.3). There was no association between study comprehension and enrollment. CONCLUSIONS AND RELEVANCE: In this study, the following factors were associated with neonatal clinical trial enrollment: demographic characteristics (ie, race/ethnicity, Medicaid status, and reported income), perception of illness, and trust in medical researchers. Future work to confirm these findings and explore the reasons behind them may lead to strategies for better engaging underrepresented groups in neonatal clinical research to reduce enrollment disparities.
There is a variability regarding timing of consent and personnel used in patient recruitment for neonatal research. We explored the associations between the study personnel and timing of consent with ...parents' decisional conflict and ultimately their decision to enroll.
This was a multi-site, cross-sectional survey conducted between August 2015 and October 2017. Participants were parents approached to enroll their 24-28-week infant in a clinical trial. Parents completed an interviewer-administered 61-item questionnaire.
Overall, 163 surveys were completed; 105 by parents of enrolled infants and 58 by parents of non-enrolled infants (54.5% participation rate). Neither the individual requesting nor timing of consent was associated with parents' knowledge score, decisional conflict, or decision to enroll. Parents preferred to be approached prenatally and by their infant's doctor.
Study designers and IRBs may allow flexibility in personnel and timing of consent as it is respectful of parents and may enhance trial enrollment.
Mucosal healing in inflammatory bowel disease (IBD) can be achieved by improvement of intestinal barrier protection. Activation of hypoxia-inducible factor (HIF) has been identified as a critical ...factor for barrier protection during mucosal insult and is linked with improvement in symptoms of colitis. Although prophylactic efficacy of HIF hydroxylase inhibitors in murine colitis have been established, its therapeutic efficacy in clinically relevant therapeutic settings have not been established. In the present study we aim to establish therapeutic efficacy of TRC160334, a novel HIF hydroxylase inhibitor, in animal models of colitis.
The efficacy of TRC160334 was evaluated in two different mouse models of colitis by oral route. A prophylactic efficacy study was performed in a 2,4,6-trinitrobenzene sulfonic acid-induced mouse model of colitis representing human Crohn's disease pathology. Additionally, a therapeutic efficacy study was performed in a dextran sulfate sodium-induced mouse model of colitis, a model simulating human ulcerative colitis.
TRC160334 treatment resulted in significant improvement in disease end points in both models of colitis. TRC160334 treatment resulted into cytoprotective heatshock protein 70 induction in inflamed colon. TRC160334 successfully attenuated the rate of fall in body weight, disease activity index, and macroscopic and microscopic scores of colonic damage leading to overall improvement in study outcome.
Our findings are the first to demonstrate that therapeutic intervention with a HIF hydroxylase inhibitor ameliorates IBD in disease models. These findings highlight the potential of TRC160334 for its clinical application in the treatment of IBD.
Current three-dimensional (3D) genome modeling platforms are limited by their inability to account for radial placement of loci in the nucleus. We present Chrom3D, a user-friendly whole-genome 3D ...computational modeling framework that simulates positions of topologically-associated domains (TADs) relative to each other and to the nuclear periphery. Chrom3D integrates chromosome conformation capture (Hi-C) and lamin-associated domain (LAD) datasets to generate structure ensembles that recapitulate radial distributions of TADs detected in single cells. Chrom3D reveals unexpected spatial features of LAD regulation in cells from patients with a laminopathy-causing lamin mutation. Chrom3D is freely available on github.
IMPORTANCE: Descriptions of the coronavirus disease 2019 (COVID-19) experience in pediatrics will help inform clinical practices and infection prevention and control for pediatric facilities. ...OBJECTIVE: To describe the epidemiology, clinical, and laboratory features of patients with COVID-19 hospitalized at a children’s hospital and to compare these parameters between patients hospitalized with and without severe disease. DESIGN, SETTING, AND PARTICIPANTS: This retrospective review of electronic medical records from a tertiary care academically affiliated children’s hospital in New York City, New York, included hospitalized children and adolescents (≤21 years) who were tested based on suspicion for COVID-19 between March 1 to April 15, 2020, and had positive results for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). EXPOSURES: Detection of SARS-CoV-2 from a nasopharyngeal specimen using a reverse transcription–polymerase chain reaction assay. MAIN OUTCOMES AND MEASURES: Severe disease as defined by the requirement for mechanical ventilation. RESULTS: Among 50 patients, 27 (54%) were boys and 25 (50%) were Hispanic. The median days from onset of symptoms to admission was 2 days (interquartile range, 1-5 days). Most patients (40 80%) had fever or respiratory symptoms (32 64%), but 3 patients (6%) with only gastrointestinal tract presentations were identified. Obesity (11 22%) was the most prevalent comorbidity. Respiratory support was required for 16 patients (32%), including 9 patients (18%) who required mechanical ventilation. One patient (2%) died. None of 14 infants and 1 of 8 immunocompromised patients had severe disease. Obesity was significantly associated with mechanical ventilation in children 2 years or older (6 of 9 67% vs 5 of 25 20%; P = .03). Lymphopenia was commonly observed at admission (36 72%) but did not differ significantly between those with and without severe disease. Those with severe disease had significantly higher C-reactive protein (median, 8.978 mg/dL to convert to milligrams per liter, multiply by 10 vs 0.64 mg/dL) and procalcitonin levels (median, 0.31 ng/mL vs 0.17 ng/mL) at admission (P < .001), as well as elevated peak interleukin 6, ferritin, and D-dimer levels during hospitalization. Hydroxychloroquine was administered to 15 patients (30%) but could not be completed for 3. Prolonged test positivity (maximum of 27 days) was observed in 4 patients (8%). CONCLUSIONS AND RELEVANCE: In this case series study of children and adolescents hospitalized with COVID-19, the disease had diverse manifestations. Infants and immunocompromised patients were not at increased risk of severe disease. Obesity was significantly associated with disease severity. Elevated inflammatory markers were seen in those with severe disease.
Background
Upfront autologous hematopoietic stem cell transplantation (AHCT) remains an important therapy in the management of patients with multiple myeloma (MM), a disease of older adults.
Methods
...The authors investigated the outcomes of AHCT in patients with MM who were aged ≥70 years. The Center for International Blood and Marrow Transplant Research (CIBMTR) database registered 15,999 patients with MM in the United States within 12 months of diagnosis during 2013 through 2017; a total of 2092 patients were aged ≥70 years. Nonrecurrence mortality (NRM), disease recurrence and/or progression (relapse; REL), progression‐free survival (PFS), and overall survival (OS) were modeled using Cox proportional hazards models with age at transplantation as the main effect. Because of the large sample size, a P value <.01 was considered to be statistically significant a priori.
Results
An increase in AHCT was noted in 2017 (28%) compared with 2013 (15%) among patients aged ≥70 years. Although approximately 82% of patients received melphalan (Mel) at a dose of 200 mg/m2 overall, 58% of the patients aged ≥70 years received Mel at a dose of 140 mg/m2. On multivariate analysis, patients aged ≥70 years demonstrated no difference with regard to NRM (hazard ratio HR 1.3; 99% confidence interval 99% CI, 1‐1.7 P = .06), REL (HR, 1.03; 99% CI, 0.9‐1.1 P = 0.6), PFS (HR, 1.06; 99% CI, 1‐1.2 P = 0.2), and OS (HR, 1.2; 99% CI, 1‐1.4 P = .02) compared with the reference group (those aged 60‐69 years). In patients aged ≥70 years, Mel administered at a dose of 140 mg/m2 was found to be associated with worse outcomes compared with Mel administered at a dose of 200 mg/m2, including day 100 NRM (1% 95% CI, 1%‐2% vs 0% 95% CI, 0%‐1%; P = .003), 2‐year PFS (64% 95% CI, 60%‐67% vs 69% 95% CI, 66%‐73%; P = .003), and 2‐year OS (85% 95% CI, 82%‐87% vs 89% 95% CI, 86%‐91%; P = .01), likely representing frailty.
Conclusions
The results of the current study demonstrated that AHCT remains an effective consolidation therapy among patients with MM across all age groups.
Upfront autologous hematopoietic stem cell transplantation (AHCT) remains an important therapy for the management of patients with multiple myeloma, which is a disease of older adults. The results of the current large database study confirm that AHCT remains an effective consolidation therapy in fit older adults aged ≥70 years.
PDF
