Increased mortality in infants with abnormal T-cell receptor excision circles.

BACKGROUND: T-Cell Receptor Excision Circles based newborn screening (TREC-NBS) allows for early detection of T-cell lymphopenia in infants with primary immunodeficiency disorders (PIDD). The utility of abnormal TREC-NBS in infants without PIDD is not well studied. We sought to evaluate the association of abnormal TREC-NBS with mortality. METHODS: 365,207 TREC-NBS from October 2011 to December 2014 were reviewed. 467 newborns had abnormal screens and did not meet the criteria for a PIDD diagnosis. Cases were matched to controls (1:3) based on gestational age, birth weight, neonatal intensive care unit status (NICU), and race. Data were obtained through NBS, birth and death certificates records from the Michigan Department of Health and Human Services (MDHHS) databases. RESULTS: Infants with abnormal TREC-NBS had higher mortality even when PIDD was ruled-out. Transient abnormal TREC-NBS was not associated with higher mortality, but unresolved or late abnormal TREC-NBS was associated with higher mortality. Infants with late abnormal TREC-NBS had severe prematurity, lower birth weight, lower Apgar scores, and higher percentage of congenital anomalies. CONCLUSION: Infants with abnormal TREC-NBS may be at a higher risk of morbidity and mortality and should be carefully followed, especially if discharged home before a repeat screen can be completed. IMPACT: This study explores the risk factors and mortality for newborns with secondary T-cell lymphopenia captured on T-Cell Receptor Excision Circles based newborn screening (TREC-NBS). Abnormal TREC-NBS allows for prompt life-saving interventions for primary immunological conditions such as Severe Combined Immunodeficiency (SCID), but can also be associated with non-immunologic conditions. Unresolved and late abnormal TREC-NBS is associated with higher mortality even without primary immunodeficiency, likely detected in infants with more severe prematurity, lower birth weight, and congenital anomalies. TREC-NBS positive infants with secondary T-cell lymphopenia require special attention and close monitoring.

Nucleated Red Blood Cell Counts Differentiate Cardiac from Respiratory Causes of Cyanosis at Birth.

Tissue hypoxia increases erythropoietin production and release of immature erythrocytes that can be measured using nucleated red blood cell counts (nRBC). We hypothesized that hypoxia due to congenital heart disease (CHD) is chronic and is better tolerated than hypoxia due to respiratory disease (RD), which is an acute stress in newborns leading to higher nRBC. This study assesses the utility of nRBC as a marker to differentiate hypoxia due to CHD vs RD in term neonates. This was a single-center, retrospective study of term neonates with cyanosis from 2015 to 2022. Neonates < 37 weeks of gestation, with hypoxic-ischemic encephalopathy, and those with other causes of cyanosis were excluded. The patients were divided into 2 groups: cyanotic CHD and cyanotic RD. Clinical and laboratory data done within 12 h and 24-36 h after birth were collected. Data are represented as median and Interquartile range. Of 189 patients with cyanosis, 80 had CHD and 109 had RD. The absolute nRBC count at ≤ 12 h of age was lower in the CHD (360 cells/mm3) compared to RD group (2340 cells/mm3) despite the CHD group having significantly lower baseline saturations. A value of 1070 cells/mm3 was highly sensitive and specific for differentiating CHD from RD. The positive predictive value for this cut-off value of 1070 cells/mm3 was 0.94 and the negative predictive value was 0.89. The absolute nRBC is a simple screening test and is available worldwide. A nRBC < 1070 cells/mm3 in cyanotic newborns should hasten the search for CHD etiology with the possible need for prostaglandin therapy.

Clinical Characteristics of Children with Eosinophilic Esophagitis and Bulbar Duodenitis.

We describe a cohort of 33 patients with eosinophilic esophagitis (EoE) and incidental duodenal bulb inflammation, termed bulbar duodenitis (BD). We conducted a single-center retrospective cohort study and recorded demographics, clinical presentation, endoscopic, and histological findings. BD was observed at the initial endoscopy in 12 cases (36%) and at a subsequent endoscopy in the remainder. Bulbar histology was usually a mix of chronic and eosinophilic inflammation. Patients were more likely to have active EoE (n = 31, 96.9%) at time of BD diagnosis. Our data indicate that the duodenal bulb of children with EoE should be carefully examined at each endoscopy and mucosal biopsies considered. Larger studies are needed to explore this association.

Infective Endocarditis at a Referral Children's Hospital During 19-Year Period: Trends and Outcomes.

BACKGROUND: We noted a recent increase in cases of infective endocarditis (IE) at our institution. The purpose of the study is to examine the incidence, risk factors, microbiology and outcome of IE in our pediatric population. METHODS: Retrospective review of IE cases during 2002-2020 at Children's Hospital of Michigan, Detroit. RESULTS: 68 patients with IE were identified. There was a 2-fold increase in incidence during the 2012-2020 (late period) compared to the 2002-2011 (early period). The most common predisposing conditions were congenital heart disease (CHD) in 39 (57.4%) and central venous catheter (CVC) in 19 (27.9%). CHD was more frequent in the late period (29/43, 67.4%) compared to early period (10/25, 40.0%) (p = 0.042). In CHD patients, palliative or corrective cardiac surgery was performed prior to IE diagnosis in 4/25 (16%) in early period and 23/43 (53.5%) in the late period (p = 0.004). S. aureus was the most common causative organism (35.3%) followed by streptococci (22.1%). Valve replacement or valvuloplasty was performed in 22.1% of patients. Complications occurred in 20 (29.4%). Mortality occurred in 7 (10.3%): 3 had CHD, 3 had CVC and underlying conditions and 1 had fulminant MRSA infection. CONCLUSION(S): The higher incidence of IE during the late period is likely due to an increase in patients with CHD who had undergone prior cardiac surgery. S. aureus was the predominant pathogen in all patients including those with CHD, followed by streptococci. IE in children continues to be associated with high rates of morbidity and mortality.

A public resource of baseline data from the Alzheimer's Prevention Initiative Autosomal-Dominant Alzheimer's Disease Trial.

INTRODUCTION: The Alzheimer's Prevention Initiative Autosomal-Dominant Alzheimer's Disease (API ADAD) Trial evaluated the anti-oligomeric amyloid beta (Aß) antibody therapy crenezumab in cognitively unimpaired members of the Colombian presenilin 1 (PSEN1) E280A kindred. We report availability, methods employed to protect confidentiality and anonymity of participants, and process for requesting and accessing baseline data. METHODS: We developed mechanisms to share baseline data from the API ADAD Trial in consultation with experts and other groups sharing data from Alzheimer's disease (AD) prevention trials, balancing the need to protect anonymity and trial integrity with making data broadly available to accelerate progress in the field. We pressure-tested deliberate and inadvertent potential threats under specific assumptions, employed a system to suppress or mask both direct and indirect identifying variables, limited and firewalled data managers, and put forth specific principles requisite to receive data. RESULTS: Baseline demographic, PSEN1 E280A and apolipoprotein E genotypes, florbetapir and fluorodeoxyglucose positron emission tomography, magnetic resonance imaging, clinical, and cognitive data can now be requested by interested researchers. DISCUSSION: Baseline data are publicly available; treatment data and biological samples, including baseline and treatment-related blood-based biomarker data will become available in accordance with our original trial agreement and subsequently developed Collaboration for Alzheimer's Prevention principles. Sharing of these data will allow exploration of important questions including the differential effects of initiating an investigational AD prevention therapy both before as well as after measurable Aß plaque deposition.

The Impact of the COVID-19 Pandemic on Mental Health, Occupational Functioning, and Professional Retention Among Health Care Workers and First Responders.

BACKGROUND: The COVID-19 pandemic has greatly affected front-line health care workers (HCW) and first responders (FR). The specific components of COVID-19 related occupational stressors (CROS) associated with psychiatric symptoms and reduced occupational functioning or retention remain poorly understood. OBJECTIVES: Examine the relationships between total and factored CROS, psychiatric symptoms, and occupational outcomes. DESIGN: Observational, self-report, single time-point online assessment. PARTICIPANTS: A total of 510 US HCW (N = 301) and FR (N = 200) with occupational duties affected by the COVID-19 pandemic. MAIN OUTCOMES AND MEASURES: CROS were assessed using a custom 17-item questionnaire. Post-traumatic stress disorder (PTSD), depression, insomnia, and generalized anxiety symptoms were assessed using the PTSD Checklist-5 (PCL5), Patient Health Questionnaire-9 (PHQ9), Insomnia Severity Index (ISI), and General Anxiety Disorder-7 (GAD7). Respondents' likelihood of leaving current field and occupational functioning were assessed with 2-item PROMIS subscales. Relationships were modeled using multivariable regression. Open-ended responses were coded using rapid template analysis. RESULTS: CROS total scores correlated significantly with all four psychiatric symptom domains (R's = .42-.53), likelihood of leaving one's current occupation (R = .18), and trouble doing usual work (R = .28), all p's < .001. Half of HCW indicated a decreased likelihood of staying in their current occupation as a result of the pandemic. CROS were fit to a 3-factor model consisting of risk, demoralization, and volume factors. All CROS factors were associated with psychiatric symptom burden, but demoralization was most prominently associated with psychiatric symptoms and negative occupational outcomes. Among psychiatric symptoms, PTSD symptoms were most strongly associated with negative occupational outcomes. Open-ended statements emphasized lack of protection and support, increased occupational demands, and emotional impact of work duties. CONCLUSIONS AND RELEVANCE: These results demonstrate potentially treatable psychiatric symptoms in HCW and FR experiencing CROS, impacting both wellbeing and the health care system. Mitigating CROS, particularly by addressing factors driving demoralization, may improve HCW and FR mental health, occupational functioning, and retention.

Nonutility of Diagnostic Testing in Ambulatory Patients With Supraventricular Tachycardia.

BACKGROUND: Supraventricular tachycardia (SVT) is the most common arrhythmia in the pediatric population. Patients often present to the emergency department and undergo extensive diagnostic assessment. The objective of this study is to determine the frequency of diagnostic studies obtained in such patients and to assess clinical significance of these results. METHODS: A retrospective study was performed from 2011 to 2018 in a single-center ED, including patients 21 years of age or younger presenting with SVT without shock. RESULTS: A total of 40 patients with 92 encounters were included for analysis. The mean age was 8.58 (±5.51) years; 55% female. A total of 67.4% underwent serologic laboratory evaluation, of which 8 (12.9%) had any abnormality. Only one was deemed clinically significant to warrant intervention. Nearly 30% of patients underwent chest radiography, with no clinically significant findings. CONCLUSIONS: Patients undergoing ED management of uncomplicated SVT are likely to undergo laboratory investigation and unlikely to have abnormal studies impacting their care. Given the associated risk of false-positive studies, the discomfort to the patient and parent, and cost of these studies, routine laboratory or radiographic investigation in this population may be unwarranted.

Sex differences in cognitive resilience in preclinical autosomal-dominant Alzheimer's disease carriers and non-carriers: Baseline findings from the API ADAD Colombia Trial.

INTRODUCTION: Females may have greater susceptibility to Alzheimer's disease (AD)-pathology. We examined the effect of sex on pathology, neurodegeneration, and memory in cognitively-unimpaired Presenilin-1 (PSEN1) E280A mutation carriers and non-carriers. METHODS: We analyzed baseline data from 167 mutation carriers and 75 non-carriers (ages 30 to 53) from the Alzheimer's Prevention Initiative Autosomal Dominant AD Trial, including florbetapir- and fludeoxyglucose-PET, MRI based hippocampal volume and cognitive testing. RESULTS: Females exhibited better delayed recall than males, controlling for age, precuneus glucose metabolism, and mutation status, although the effect was not significant among PSEN1 mutation carriers only. APOE ε4 did not modify the effect of sex on AD biomarkers and memory. DISCUSSION: Our findings suggest that, among cognitively-unimpaired individuals at genetic risk for autosomal-dominant AD, females may have greater cognitive resilience to AD pathology and neurodegeneration than males. Further investigation of sex-specific differences in autosomal-dominant AD is key to elucidating mechanisms of AD risk and resilience.

Aerosolized Beractant in neonatal respiratory distress syndrome: A randomized fixed-dose parallel-arm phase II trial.

PURPOSE: There is increasing research into novel techniques of administering surfactant to preterm infants (PTIs) with respiratory distress syndrome (RDS) receiving non-invasive respiratory support (NIRS). Although aerosolized surfactant (AS) is promising in PTIs receiving NIRS, the optimal surfactant dose and formulation, drug-device combination and patient profile is not known. The objective of this randomized clinical trial was to investigate the feasibility, safety, efficacy and impact of four dosing schedules of AS using two nebulizers in PTIs with RDS stratified by gestational age (GA). METHODS: PTIs with RDS receiving pre-defined NIRS for ≤8 h were assigned to 4 A S dosing schedules and 2 nebulizers within three GA strata (I = 240/7-286/7, II = 290/7-326/7, III = 330/7-366/7 weeks). There was no contemporaneous control group; at the recommendation of the Data Monitoring Committee, data was collected retrospectively for control infants. RESULTS: Of 149 subjects that received AS, the median age at initiation of the 1st dose and duration was 5.5 and 2.4 h respectively. There were 29 infants in stratum I, and 60 each in strata II and III. Of infants <32 weeks GA, 94% received caffeine prior to AS. Fifteen infants (10%) required intubation within 72 h; the rates were not significantly different between GA strata, dosing schedules and nebulizers for infants who received aerosolized surfactant. Compared to retrospective controls, infants who received AS were less likely to need intubation within 72 h in both the intention-to-treat (32% vs. 11%) and the per-protocol (22% vs. 10%) analyses (p < 0.05) with GA stratum specific differences. AS was well tolerated by infants and clinical caregivers. Commonest adverse events included surfactant reflux from nose and mouth (18%), desaturations (11%), and increased secretions (7%). CONCLUSIONS: We have demonstrated the feasibility, absence of serious adverse events and short-term efficacy of four dosing schedules of AS in the largest Phase II clinical trial of PTIs 24-36 weeks' GA with RDS receiving NIRS (ClinicalTrials.gov NCT02294630). The commonest adverse events noted were surfactant reflux and desaturations; no serious adverse effects were observed. Infants who received AS were less likely to receive intubation within 72 h compared to historical controls. AS is a promising new therapy for PTIs with RDS.

Power and sample size for random coefficient regression models in randomized experiments with monotone missing data.

Random coefficient regression (also known as random effects, mixed effects, growth curve, variance component, multilevel, or hierarchical linear modeling) can be a natural and useful approach for characterizing and testing hypotheses in data that are correlated within experimental units. Existing power and sample size software for such data are based on two variance component models or those using a two-stage formulation. These approaches may be markedly inaccurate in settings where more variance components (i.e., intercept, rate of change, and residual error) are warranted. We present variance, power, sample size formulae, and software (R Shiny app) for use with random coefficient regression models with possible missing data and variable follow-up. We illustrate sample size and study design planning using data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. We additionally examine the drivers of variability to better inform study design.

Recruitment of a multi-site randomized controlled trial of aerobic exercise for older adults with amnestic mild cognitive impairment: The EXERT trial.

INTRODUCTION: Effective strategies to recruit older adults with mild cognitive impairment (MCI) into nonpharmacological intervention trials are lacking. METHODS: Recruitment for EXERT, a multisite randomized controlled 18-month trial examining the effects of aerobic exercise on cognitive trajectory in adults with amnestic MCI, involved a diverse portfolio of strategies to enroll 296 participants. RESULTS: Recruitment occurred September 2016 through March 2020 and was initially slow. After mass mailings of 490,323 age- and geo-targeted infographic postcards and brochures, recruitment rates increased substantially, peaking at 16 randomizations/month in early 2020. Mass mailings accounted for 52% of randomized participants, whereas 25% were recruited from memory clinic rosters, electronic health records, and national and local registries. Other sources included news broadcasts, public service announcements (PSA), local advertising, and community presentations. DISCUSSION: Age- and geo-targeted mass mailing of infographic materials was the most effective approach in recruiting older adults with amnestic MCI into an 18-month exercise trial.

Non-pharmaceutical Interventions and the Infodemic on Twitter: Lessons Learned from Italy during the Covid-19 Pandemic.

The COVID-19 pandemic changed expectations for information dissemination and use around the globe, challenging accepted models of communications, leadership, and social systems. We explore how social media discourse about COVID-19 in Italy was affected by the rapid spread of the virus, and how themes in postings changed with the adoption of social distancing measures and non-pharmaceutical interventions (NPI). We used topic modeling and social network analysis to highlight critical dimensions of conversations around COVID-19: 1) topics in social media postings about the Coronavirus; 2) the scope and reach of social networks; and 3) changes in social media content as the nation moved from partial to full social distancing. Twitter messages sent in Italy between February 11th and March 10th, 2020. 74,306 Tweets sent by institutions, news sources, elected officials, scientists and social media influencers. Messages were retweeted more than 1.2 million times globally. Non-parametric chi-square statistic with residual analysis to identify categories, chi-square test for linear trend, and Social Network Graphing. The first phase of the pandemic was dominated by social media influencers, followed by a focus on the economic consequences of the virus and placing blame on immigrants. As the crisis deepened, science-based themes began to predominate, with a focus on reducing the spread of the virus through physical distancing and business closures Our findings highlight the importance of messaging in social media in gaining the public's trust and engagement during a pandemic. This requires credible scientific voices to garner public support for effective mitigation. Fighting the spread of an infectious disease goes hand in hand with stemming the dissemination of lies, bad science, and misdirection.

The Effectiveness of Methylprednisolone as a Premedication Among the Pediatric Population for Preventing Infusion-Related Reactions to Infliximab.

Administering medications prior to infliximab infusions to prevent infusion-related infliximab reactions is a common practice in the United States. However, the premedication protocol varies among different institutions. The purpose of this study was to demonstrate whether the use of methylprednisolone was effective as a premedication to prevent infusion reactions while infliximab was administered to children with inflammatory bowel disease. The effect of concurrent use of other immunomodulators on the rate of reaction incidents was also studied. This was a retrospective chart review, assessing children younger than 21 years diagnosed with inflammatory bowel disease from January 2008 to April 2018. The incident rate of infusion reactions was also compared between two cohorts: those who received the premedication of methylprednisolone and those who did not. Subgroup analysis of concomitant immunomodulators, infliximab dose and frequency, and anti-infliximab assay were also performed. A total of 34 subjects received methylprednisolone as a premedication and 151 subjects did not. No statistically significant difference of allergic reactions was found between the two groups (p = .727). Concomitant immunomodulator therapy lowered the likelihood of developing reactions (p = .048). This study was conducted to help pediatric gastroenterology and infusion nurses better understand and implement evidence-based approaches in the premedication protocol for infusions of anti-tumor necrosis factor-α (anti-TNF-α) antibody products.

Response to reduced dietary protein level on growth performance in growing Windsnyer pigs.

The objective of the study was to determine the growth performance response to reduced dietary protein level and to identify the optimum level of protein for the performance in growing Windsnyer pigs. Maize-soybean-based diets were formulated to contain a protein level of 193 g/kg, 173.7 g/kg, 154.4 g/kg, 135.1 g/kg, 115.8 g/kg and 96.5 g/kg. The 193 g/kg (control diet) is the standard recommended by the National Research Council. The amino acid levels and net energy value were similar in all treatments. The study was conducted with five growing Windsnyer pigs per each protein inclusion level. The trial was carried out with individually caged pigs aged 4 months, weighing about 23 (SD = 1.39) kg. The experiment lasted a period of 8 weeks excluding 2 weeks of the adaptation period. The feed and water were offered ad libitum. The average daily feed intake (ADFI), average daily gain (ADG), feed conversion ratio (FCR), final body weight (FBW) and metabolic body weight (BW0.75) were measured. Polynomial regression and piecewise regressions were used to analyse data. Decremental levels of protein did not affect (p > 0.05) ADFI and ADG. Reduced levels of protein influenced FBW, BW0.75 and FCR (p < 0.05). A decreasing quadratic response was observed in FCR, as CP decreased from 193 g/kg to 135.1, FCR improved from 3.18 to 2.13 then suddenly decreased with the CP level. There was a quadratic increase in BW0.75 and FBW as inclusion levels of protein were reduced (p < 0.05). They increased from 193 g/kg (FBW 39.5 and BW0.75 12.8) protein level until 135.1 g/kg (FBW 45.1 and BW0.75 14.6) then begun to decrease as dietary protein level was decreased further. Using stepwise piece (broken stick) methods, the optimum protein level for FCR was estimated to be at 135.1 g/kg (p < 0.05). The maximum level of dietary protein for BW and BW0.75 was obtained at 135.1 g/kg. Reduction of the CP level in the Windsnyer pig diet beyond 138.3, 132.1 and 132.3 g/kg hinders the FCR, FBW and BW0.75, respectively. Protein levels can be reduced from the standard recommendation level of 193 g/kg to 135.1 g/kg without compromising the growth performance of growing Windsnyer pigs.

Cytomegalovirus viremia and resistance patterns in immunocompromised children: An 11-year experience.

We noted a recent increase in number of immunocompromised children with CMV viremia at our institution. The purpose of this study was to determine the frequency of CMV viremia in this population and evaluate factors associated with drug-resistant mutations. A retrospective review of immunocompromised hosts, 0-21 years of age, who had CMV viremia during 2007-2017. CMV viremia was detected using PCR assays. Genetic mutation assays were performed using PCR sequencing of the phosophotransferase UL 97 gene and the polymerase UL54 gene of CMV using Quest Diagnostics (San Juan Capistrano, CA, USA) or ARUP Labs (Salt Lake City, UT, USA). Thirty-one patients were identified, including 10 (32%) during the last 2 years. Of the 31 patients, 18 had hematopoietic stem cell transplantation (HSCT), 5 had primary immunodeficiency, 4 had malignancies, 3 had heart transplantation and 1 had new Human Immunodeficiency virus (HIV) infection. Antiviral resistance testing was performed on isolates from seven patients: five with persistent viremia (>1 mo), and two prior to starting antiviral therapy. Resistance was identified in three patients' isolates: two with common variable immunodeficiency (CVID) and one with recurrent Hodgkin's lymphoma who had undergone autologous HSCT. The two patients with CVID had chronic diarrhea and malabsorption and had received prolonged oral valganciclovir courses prior to emergence of resistance. The patient with Hodgkin's lymphoma had received a prolonged IV ganciclovir course. All three tested positive for UL97 mutation and two had both UL97 and UL54 gene mutations. Majority of our patients (21/31) with CMV viremia were transplant recipients and ganciclovir resistance developed in 10%. Two had intestinal malabsorption. Treatment with oral valganciclovir should be avoided in patients with poor gut absorption as that may increase the risk of resistance.

Baseline demographic, clinical, and cognitive characteristics of the Alzheimer's Prevention Initiative (API) Autosomal-Dominant Alzheimer's Disease Colombia Trial.

INTRODUCTION: The API AutosomalDominant AD (ADAD) Colombia Trial is a placebo-controlled clinical trial of crenezumab in 252 cognitively unimpaired 30 to 60-year-old Presenilin 1 (PSEN1) E280A kindred members, including mutation carriers randomized to active treatment or placebo and non-carriers who receive placebo. METHODS: Of the 252 enrolled, we present data on a total of 242 mutation carriers and non-carriers matched by age range, excluding data on 10 participants to protect participant confidentiality, genetic status, and trial integrity. RESULTS: We summarize demographic, clinical, cognitive, and behavioral data from 167 mutation carriers and 75 non-carriers, 30 to 53 years of age. Carriers were significantly younger than non-carriers ((mean age ± SD) 37 ± 5 vs 42 ± 6), had significantly lower Mini Mental Status Exam (MMSE) scores (28.8 ± 1.4 vs 29.2 ± 1.0), and had consistently lower memory scores. DISCUSSION: Although PSEN1 E280A mutation carriers in the Trial are cognitively unimpaired, they have slightly lower MMSE and memory scores than non-carriers. Their demographic characteristics are representative of the local population.

Utility of thromboelastography for the diagnosis of von Willebrand disease.

Von Willebrand disease (VWD) is an inherited bleeding disorder that is caused by a quantitative or qualitative deficiency of von Willebrand factor (VWF). The National Heart, Lung, and Blood Institute (NHLBI) guidelines for the diagnosis of VWD state that a VWF activity (VWF:RCo) of <30 IU/dL or <50 IU/dL with symptoms of clinical bleeding are consistent with the diagnosis of VWD. However, current gold-standard diagnostic testing takes days to have complete results. Thromboelastography (TEG) is a testing method that provides a graphical trace that represents the viscoelastic changes seen with fibrin polymerization in whole blood, therefore providing information on all phases of the coagulation process. This study describes the TEG characteristics in 160 patients who presented for workup of a bleeding disorder and a subset of those were subsequently diagnosed with VWD. The TEG parameters, K-time (representing the dynamics of clot formation) and the maximal rate of thrombus generation (MRTG), were found to be sensitive in detecting patients with VWF:RCo <30 IU/dL. The TEG, unlike VWF:RCo, can be done in real time, and results are available to the clinician within an hour. This will definitely be beneficial in acute situations such as evaluation of and management of acute bleeding in patients with acquired deficiencies of VWF and may play an important role in the surgical management of patients with VWD.

Clinical Trial Enrollment is Associated With Improved Follow-up Rates Among Survivors of Childhood Cancer.

Fortunately >80% of children diagnosed with cancer become long-term survivors; however, this population is at a significantly increased risk of morbidity and mortality as a result of their previous cancer therapy, and long-term follow-up (LTFU) is critical. Multiple barriers to receiving adequate LTFU care have been studied. We investigated whether lack of enrollment in a therapeutic clinical trial may be a barrier to receiving LTFU care. We conducted a review of 353 patient records at the Children's Hospital of Michigan enrolled in our Children's Oncology Group registry between January 1, 2005 and December 31, 2010. In total, 71 patients were excluded (death before follow-up, n=61; currently receiving therapy, n=5; known transfer of care, n=4; insufficient information, n=1). In total, 158 (56%) patients were enrolled in a therapeutic clinical trial. Follow-up rates at 1-, 2- and 5-years following completion of therapy for patients enrolled in a therapeutic clinical trial were 96.8% (153/158), 93.7% (148/158), and 81.7% (103/126), respectively, compared with 83.1% (103/124; P<0.001), 74.2% (92/124; P<0.001), and 66.7% (72/108; P=0.001) for patients not enrolled. Our findings suggest patients enrolled in a therapeutic clinical trial have better LTFU rates and supports the importance of patient enrollment in therapeutic clinical trials when possible. Additional resources may be warranted to improve LTFU for patients not enrolled.

Higher daily doses of caffeine lowered the incidence of moderate to severe neurodevelopmental disabilities in very low birth weight infants.

AIM: We determined the influence of cumulative dosing of caffeine citrate on the neurodevelopmental outcomes of low birth weight (VLBW) infants at 18-22 months of postmenstrual age. METHODS: This retrospective chart analysis was conducted at Detroit Medical Center, Michigan, USA. The 181 infants we included were born between January 2006 and December 2016, were less than 32 weeks of gestational age and weighed less than 1500 grams. Data on their perinatal and postnatal characteristics were retrieved from their medical records and they were assessed using the Bayley Scales of Infant Development - Third Edition. RESULTS: The 64 infants with no neurodevelopmental disability or a mild disability received a significantly higher average daily dose (mg/kg/day) of caffeine citrate with a median of 7.58 (range 2.7-12.2) mg/kg/day, than the 79 infants with a moderate to severe disability, who received a median of 6.47 (range 3.1-12.5, p = 0.01). The total cumulative dose had no effect on bronchopulmonary dysplasia or neurodevelopmental outcomes. CONCLUSION: A higher average daily dose of caffeine citrate was associated with better neurodevelopmental outcomes of VLBW infants. However, the cumulative dose did not have an impact on their short-term or long-term outcomes. Further research is needed to confirm our findings.

A randomized clinical trial to evaluate home-based assessment of people over 75 years old.

INTRODUCTION: There is an unmet need for effective methods for conducting dementia prevention trials. METHODS: Home-based assessment study compared feasibility and efficiency, ability to capture change over time using in-home instruments, and ability to predict cognitive conversion using predefined triggers in a randomized clinical trial in (1) mail-in questionnaire/live telephone interviews, (2) automated telephone/interactive voice recognition, and (3) internet-based computer Kiosk technologies. Primary endpoint was defined as cognitive conversion. RESULTS: Analysis followed a modified intent-to-treat principle. Dropout rates were low and similar across technologies but participants in Kiosk were more likely to dropout earlier. Staff resources needed were higher in Kiosk. In-home instruments distinguished conversion and stable groups. Cognitively stable group showed improvement in cognitive measures. Triggering was associated with higher likelihood of conversion but statistically significant only in mail-in questionnaire/live telephone interviews. DISCUSSION: Relatively low efficiency of internet-based assessment compared with testing by live-assessors has implications for internet-based recruitment and assessment efforts currently proposed for diverse populations.