United States

Small-for-gestational-age (SGA) children may be at risk for earlier puberty and adverse long-term health sequalae. This study investigates associations between SGA and age at menarche using secondary data analysis of 992 female children in a U.S. birth cohort of primarily non-marital births. SGA was defined as &lt;10th percentile of weight for gestational age within the sample. We estimated unadjusted and adjusted Ordinary Least Squares (OLS) models of associations between SGA and age at menarche in years, as well as unadjusted and adjusted logistic regression models of associations between SGA and menarche before age 11. SGA was associated with slightly earlier menarche, but the difference was not statistically significant even when adjusting for maternal sociodemographic characteristics and when further adjusting for prenatal smoking and maternal pre-pregnancy overweight and obesity. Similarly, SGA was not significantly associated with the odds of menarche before age 11 in unadjusted or adjusted models. Maternal non-Hispanic Black race-ethnicity, Hispanic ethnicity, and pre-pregnancy obesity all had independent associations with earlier age at menarche and menarche before age 11. Therefore, it appears that inherited maternal risk factors play more direct roles.

AMA Research Challenge 2023

SGA and age at menarche in a diverse population-based U.S. sample

Small-for-gestational-age (SGA) children may be at risk for earlier puberty and adverse long-term health sequalae. This study investigates associations between SGA and age at menarche using secondary data analysis of 992 female children in a U.S. birth cohort of primarily non-marital births. SGA was defined as <10th percentile of weight for gestational age within the sample. We estimated unadjusted and adjusted Ordinary Least Squares (OLS) models of associations between SGA and age at menarche in years, as well as unadjusted and adjusted logistic regression models of associations between SGA and menarche before age 11. SGA was associated with slightly earlier menarche, but the difference was not statistically significant even when adjusting for maternal sociodemographic characteristics and when further adjusting for prenatal smoking and maternal pre-pregnancy overweight and obesity. Similarly, SGA was not significantly associated with the odds of menarche before age 11 in unadjusted or adjusted models. Maternal non-Hispanic Black race-ethnicity, Hispanic ethnicity, and pre-pregnancy obesity all had independent associations with earlier age at menarche and menarche before age 11. Therefore, it appears that inherited maternal risk factors play more direct roles.

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Background: Hydrogenogenic small intestine bacterial overgrowth (SIBO) has been associated with growth stunting and neurodevelopmental deficits in children from low and middle-income countries. However, methanogenic overgrowth has yet to be studied in this population. We sought to determine if increased methane levels on glucose breath tests (GBT) could predict growth and neurodevelopment.
Methods: GBT was performed at 6, 12, and 18 months on Tanzanian infants as part of the Early Life Interventions for Childhood Growth and Development in Tanzania (ELICIT) study conducted in rural Tanzania. Area under the methane curve was calculated and averaged over the three tests (CH4 AUC). Neurodevelopment was assessed using the Malawi Developmental Assessment Tool (MDAT).
Results: Univariate and multivariate linear regressions were performed to determine if CH4 AUC predicted growth or neurodevelopment and to determine predictors driving CH4 AUC levels. There was significant seasonal variation in CH4 AUC levels per child birth-month, with the highest levels associated with the spring months (March-May). Multivariable analysis showed no significant association between CH4 AUC and length-for-age Z score at 18 months, MDAT total score, or MDAT component scores. Birth month was a significant predictor of CH4 AUC (F= 66.614, p<.001). However, when analyzing patients with significant methanogenic SIBO (as determined by the top 50% of valid CH4 AUC values), antimicrobial administration had a positive but non-significant association with growth LAZ18 ( p=0.05), and nicotinamide administration revealed a significant association for LAZ18 when controlling for significant descriptive variables ( p=0.005) as compared to antimicrobial and nicotinamide administration in patients with negligible methanogenic SIBO (p=0.08, p=0.53, respectively).
Conclusion: This initial study does support a relationship between methanogenic overgrowth and growth stunting through the positive growth effect in positive SIBO children who received nicotinamide treatment, an effect that was not seen in the children without SIBO. Further study is needed to understand the relationship between methanogenic overgrowth and environmental enteric dysfunction and/or gastrointestinal symptomatology.

Analyses of Methanogenic Small Intestine Overgrowth Effects on Growth in Tanzanian Children

Background: 
There are many short and long-term benefits of breastfeeding or providing expressed breast milk (EBM). Colostrum, the first milk produced after birth, has the highest concentration of immune-protective biofactors. When born < 34 weeks gestational age (GA), infant’s oral motor skills limit their ability to orally feed. To overcome this barrier and promote exposure to EBM, oral colostrum care (OCC) allows for the administration of EBM in preterm infants. Promoting OCC may lead to an increase in EBM feedings with earlier establishment of lactogenesis. In April 2019, our neonatal intensive care unit (NICU) initiated a policy for OCC use for all inborn infants < 32 weeks GA for the first 7 days of life (DOL).

Objective: 
Describe OCC practice after implementation of policy in the Children’s Memorial Hermann Hospital (CMHH) level 4 NICU and quantify the impact of OCC on use of EBM at discharge.

Methods:
A three-year retrospective cohort study from January 2019 through May 2022 included inborn infants < 32 weeks GA. During this period, n=1184 qualified for OCC, 25 infants were randomly sampled per year. The infants were divided into two groups: those who received OCC and those who received no OCC. Categorical and continuous variables were compared using Fisher's exact test and the Mann-Whitney U test, respectively. 

Results:
Included in the analysis were OCC infants (n= 92) and non-OCC infants (n=8). Both groups were comparable in baseline characteristics except OCC infants were an average of 16 days younger than non-OCC infants (p=0.031). Length of stay was more than double in OCC infants compared to non-OCC infants (52.5 vs 25.0 days, p=0.072). No difference appreciated between groups in feeding outcomes within 72 hours of discharge (p=0.157). 1.1% OCC infants received exclusive human milk (either donor human milk ((DHM) or EBM), compared to 12.5% non-OCC infants received exclusive human milk. 58.7% OCC infants received formula, compared to 37.5% non-OCC infants received formula. 38% OCC infants received fortified human milk (either DHM or EBM) and formula, compared to 50% of non-OCC infants (p=0.157). No difference in hours after birth the infant received first EBM (66 vs 52 hours, p=0.434) or for documented EBM volume throughout hospitalization (2332.5 mL vs 2573 mL, p=0.722) between OCC infants and non-OCC infants. 

Conclusions: 
OCC use occurred in 92% of our sample. Non-OCC infants had greater exclusive human milk volume within 72 hours of discharge, greater parental visits, received first EBM sooner, and had greater EBM volume received throughout hospitalization.

Oral Colostrum Care to Predict Expressed Breast Milk at Discharge

Cerebral palsy (CP) is the leading cause of childhood physical disability. Children with CP receive several therapies designed to improve gross motor skills, but further research is needed to understand the impact of these therapies on motor learning and optimal therapeutic dose.
The aim of this study is to compare motor learning and variability between children with CP and typically developing (TD) children. We hypothesize that (1) children with CP and TD children will have differing patterns of motor learning, and (2) children with CP will show greater variability in motor learning compared to TD peers, but this variability will reduce for both groups with training.
The motor task involved a stability platform. Participants were instructed to keep the platform within 5 degrees of its horizontal position. Training consisted of 15, 30 s trials/day for 5 days, pre- and post-testing were 5, 30 s trials/day. Performance was determined by quantifying time the participant maintained the platform within 5 degrees of horizontal and variability by time spent on either side of the 5 degrees.
Mixed-model ANOVA was performed with time (pre-test vs. post-test) as the within-subject variable and group (CP vs. TD) as the between-subject variable. Dependent variables were mean center time and variability. 
TD children improved an average of 6.7 seconds (20.8 s to 27.5 s) from pre-test to post-test. Children with CP improved an average of 11.9 seconds (9.85 to 21.7 s). TD children decreased variability an average of 3.35 seconds (4.58 to 1.23 s). Children with CP decreased variability an average of 6 seconds (10.1 to 4.1 s). 
ANOVA showed significant main effects for time on mean center time (F (1,40) = 26.0, p < 0.001) and group on mean center time (F (1,40) = 20.9, p < 0.001), as well as time on variability (F (1,40) = 1, p < 0.001) and group on variability (F (1,40) = 1, p < 0.001). 
Both groups showed motor learning with five days of balance training. Children with CP showed greater variability in their balance performance than TD children. 
While TD children achieved almost maximum performance with training, children with CP may need more training to achieve this same performance. Alternatively, children with CP may reach maximum motor learning potential after a certain dose, therefore requiring other therapeutic interventions. Participant recruitment and data collection is ongoing.

Differences in Motor Learning Between Children with Cerebral Palsy and Typically Developing Peers Using a Dynamic Balance Task

Background:
Alzheimer's Disease (AD) is a progressive neurodegenerative disease that causes cognitive and functional impairments. Abnormal amyloid plaque accumulation is known to be specific for AD, demonstrated by previous amyloid Positron Emission Tomography (PET) studies showing abnormal amyloid plagues levels in subjects in the early stages of the disease, not exhibiting clinical manifestations. This study explores the possible relationship between the amyloid plaque level visible on amyloid PET scans and non-specific Physical Performance Tests such as Timed Up and Go (TUG) among subjects.


Methods: 
Data were analyzed on n= 2076 Participants (from the Health and Aging Brain Study- Health Disparities). All participants underwent as part of the HABS-HD protocol cognitive testing, functional/medical examination, blood draw, and neuroimaging. Amyloid PET scans were conducted with defined regions of intertest (ROIs) in the brain. All participants completed the Timed UP and Go (TUG) test along with other gait measures as part of the functional examine. Chi-square (Sex) and t-tests (Age, Education, TUG performance) were used to examine differences in demographic characteristics across ethnic groups. Linear regression models were conducted to examine the relationship between Amyloid PET imaging and a functional measure (TUG) and the significance was set at p<0.05


Results: 
In our study, we found a statistically significant correlation between TUG time and increased amyloid uptake only in the lateral parietal region in Mexican American subjects (p=0.049). The other ROIs in Mexican American subjects showed no statistically significant correlation between TUG time and increased amyloid uptake. 

Conclusion: 
This study aimed to examine the relationship between physical performance measures (such as the TUG) and amyloid uptake. Using PET scans, we theorized that TUG results might correlate with the amyloid plaque level; However, our results were inconsistent with our initial hypothesis. However, this study did reveal a correlation between TUG time and increased amyloid uptake (only in the lateral parietal region) with subjects of Mexican descent, therefore; highlighting the importance of exploring ethnic differences in AD research. Finally, this study is limited by a small sample size, and future work with additional samples should help examine the TUG and amyloid uptake relationship and ethnic differences.

Correlation Between Timed Up and Go Test and Neuroimaging in Mexican American and Non-Hispanic Americans with Alzheimer’s Disease

Background 
Dynamic lumbar instability evaluated on flexion-extension radiographs has been a longstanding convention in clinical decision-making for the management of low back pain by interventionalists and surgeons. However, these radiographs often underestimate the degree of lumbar spondylolisthesis, limiting their diagnostic utility. Significant variability remains in current guidelines regarding the most appropriate imaging modalities to adequately evaluate instability. Thus, identifying more efficacious imaging techniques to improve diagnostic utility, minimize radiation exposure, and reduce unnecessary healthcare costs is warranted. We compared different diagnostic images of single-level anterior spondylolisthesis and hypothesize that positional changes will affect the degree of dynamic instability, with spondylolisthesis observed in prone position providing greater sensitivity for instability compared to standing or supine positions. 

Methods 
Single center retrospective cohort of L4-5 anterolisthesis between 2014 – 2022 with standing radiographs (CR), prone CT scans (CT), or supine MRI images (MRI). Exclusion criteria: presence of lumbar hardware, patients with missing imaging modalities (either CR, CT or MRI), time between any modalities exceeding 13 months, no evidence of anterolisthesis, or poor image quality precluding the ability to fully visualize and assess spondylolisthesis. 

Results 
The average translation (± SD) measured were 4.9 ± 2.2 mm (CR), 2.5 ± 2.6 mm (CT), and 3.7 ± 2.6 mm (MRI) (p < 0.001). The mean difference in anterolisthesis among imaging modalities were 2.7 ± 1.8 mm between CR and CT (p < 0.001) and 1.8 ± 1.4 mm between CR and MRI (p < 0.001). Ninety two of 102 patients (90.2%) showed greater anterolisthesis on CR compared to CT, 72 of 102 (70.6%) comparing CR to MRI, and 27 of 102 (26.5%) comparing CT to MRI.  

Comparing CR with MRI, we found that 17.6% of patients exhibited > 3 mm anterior translation, whereas 38.2% patients were identified comparing CR with CT imaging, indicating a 20.6% difference in missed lumbar instability (χ2 test p = 0.0009, post-hoc Fisher’s exact test p = 0.0006 between CR and CT). Only a small percentage of patients showed increased segmental translation between flexion-standing (5.9%) and extension-standing radiographs (11.8%). We identified comparable results using 2 mm and 4.5 mm thresholds. 

Conclusion 
Comparing standing CR versus prone CT revealed the greatest degree of single level lumbar segmental translation (L4-5. Prone positioning also significantly reduced L4-5 anterolisthesis compared to flexion-extension standing X-rays, suggesting that comparing prone positioning to standing lateral views may increase detection of dynamic instability at L4-5 compared to standard stress views.

Dynamic Instability is Underestimated on Standing Flexion-Extension films when compared to Prone CT Imaging

Background
The purpose of this research is to test the clinical validity of a computerized version of the Trail Making Test (TMT) in an acute rehabilitation center for predicting concurrent inpatient disability. The TMT is a widely used neuropsychological assessment that has been shown to predict brain damage. Despite its value and efficacy in testing cognitive function, the TMT is limited to patients who have intact manual dexterity because it requires using a pen. Individuals with conditions that limit manual use (e.g. bone fracture, paralysis, burns, etc.) cannot take the test. Although there are adapted TMTs to include these populations, not many of these tests still involve visual interaction. Assessment of executive function using the Computer-Assisted TMT (CTMT) has already shown to be feasible in rehabilitation patients with intact manual dexterity. This study tested the Computer-Assisted TMT (CTMT) in rehabilitation patients who lack motor hand use.
Methods
This cross-sectional study was conducted in an acute rehabilitation hospital setting with patients (n = 37) who lack hand usability with either hand. Because patients with brain illness may have slower speech, the CTMT scores were corrected for maximal oral speech rate. Participants were tested in their hospital rooms over two sessions of the CTMT to evaluate test-retest reliability. Test-retest reliability was evaluated with Pearson correlation.
Results
50 patients were approached to be in the study, and 37 of them consented to participate. Out of the 37 participants, 33 participants were able to complete one round of testing and 17 participants were able to complete both rounds of testing. Time for CTMT completion was corrected by the maximal speech production rate (diadochokinesis or DDK). Since DDK rate has shown to be modulated by age, we also corrected people 47 years and older by a factor of 0.9316, which is based on previous research. The CMT versions had excellent test-retest reliability (r = 0.93 for CTMT-A, r = 0.83 for CTMT-B, and r =0.92 for CTMT-3).
Conclusion
The results of this study could help to determine if the CTMT can reliably predict concurrent physical disability and inform new forms of cognitive rehabilitation.


The Validation of a Computer-Assisted Trail Making Test in Acute Rehabilitation Inpatients with Manual Disability

Purpose: Buccal myomucosal flaps (BMF) provide an alternative for anatomic lengthening of the palate in the treatment of velopharyngeal insufficiency (VPI). We systematically reviewed the existing data on speech outcome of BMF palatal lengthening.

Methods: English-language prospective and retrospective studies assessing speech improvement following BMF palatal lengthening were identified using Ovid, Pubmed, and Embase. Studies without objective speech measurements were excluded. PRISMA guidelines were followed, and articles’ quality was assessed. A random effects model meta-analyses were performed for hypernasality, intelligibility, and nasal emission score improvements, which were derived from reported preoperative and postoperative scores, and controlled for variability of scales and timing of postoperative assessment. Chi-squared tests assessed surgical techniques, patients’ languages, and mean age.

Results: Out of initial 7115 articles, 13 were included in this review. All 13 met NIH Quality Assessment Tool criteria. 7 retrospective studies evaluated a total of 283 patients and 6 prospective studies evaluated 165 patients. The most common surgical indications for BMF were large size of the velopharyngeal gap (7 papers) and prior surgery for VPI (5 papers). Meta analyses for hypernasality, intelligibility, and nasal emission score improvements demonstrated effect sizes above zero, confirming the utility of BMF in VPI treatment. Egger regressions and funnel plots revealed low risk of publication bias. There were no significant variations in speech outcomes among surgical techniques, patients’ languages, or mean age.

Conclusions: Buccal myomucosal flaps provide reliable treatment for VPI in patients with large velopharyngeal gap size and a history of prior unsuccessful surgery.

Speech Outcomes of Buccal Myomucosal Flap Palatal Lengthening Treatment of Velopharyngeal Insufficiency: Systematic Literature Review and Meta Analysis

Background:

Frailty increases the likelihood of complications after breast reconstruction, yet there has been limited research on how it affects long-term outcomes. We investigated the relationship between the 5-item modified frailty index (mFI) score with both surgical and patient-reported outcomes in microvascular breast reconstruction.

Methods:

We conducted a retrospective cohort study of patients who underwent mastectomy and microvascular breast reconstruction between January 2016 and April 2022. Primary outcome was any flap-related complication and secondary outcomes included patient-reported outcomes and factors that predicted complications in frail patients.

Results: 

We identified 1640 breast reconstructions, with a mean follow-up period of 24.2±19.2 months. Patients with an mFI score ≥2 had greater odds of experiencing surgical complications (OR, 2.13, p=0.023) and medical complications (OR 17.02, p<0.001) than non-frail patients. However, we found no significant difference in breast satisfaction (p=0.287), psychosocial well-being (p=0.119), or sexual well being (p=0.314) based on the mFI score. Chronic obstructive pulmonary disease was a predictor of infection (OR 3.70, p=0.002), while tobacco use (OR 7.13, p=0.002) and contralateral prophylactic mastectomy (OR 2.36, p=0.014) were predictors of wound dehiscence. Skin flap necrosis was more likely in patients with dependent functional status (OR 2.36, p=0.007) and in those who underwent immediate reconstruction (OR 3.16, p=0.026). Dependent functional status was also associated with higher odds of reoperation (OR 2.64, p=0.011).

Conclusion: 

While frailty increases the likelihood of complications in breast reconstruction, there is no notable difference in long-term patient-reported outcomes. The mFI score should be incorporated in breast reconstruction to optimize outcomes in high-risk, frail patients.

Impact of the 5-item Modified Frailty Index on Long-term Surgical and Patient-reported Outcomes in Microvascular Breast Reconstruction

Background: Smartphone-based thermal imaging (SBTI) has been reported in
the literature to be an easy-to-use, contactless, cost-friendly alternative to standard
imagingmodalities in identifying flap perforators,monitoring flap perfusion, and
detecting flap failure. Our systematic review and meta-analysis aimed to evaluate
SBTI's accuracy in perforator identification and secondarily evaluate SBTI's utility
in flap perfusion monitoring as well as ability to predict flap compromise, failure,
and survival.
Methods: Following Preferred Reporting Items for Systematic Reviews and
Meta-Analysis guidelines, a systematic review was performed using PubMed
from inception to 2021. Articles were uploaded into Covidence and, following
duplicate deletion, were initially screened for use of SBTI in flap procedures
through title and abstract screening followed by full-text review. The following
data points, if provided, were extracted from each included study: study design,
number of patients, patient demographics, perforator number and location, flap
number and location, room temperature, cooling method, imaging distance, time
from cloth removal, primary (SBTI's accuracy in perforator identification), and
secondary outcomes (prediction of flap compromise/failure/survival and cost
analysis). Meta-analysis was performed using RevMan v.5.
Results: The initial search yielded 153 articles. Eleven applicable studies with a
total of 430 flaps from 416 patients were ultimately included. The SBTI device
assessed in all included studies was FLIR ONE. Four studies assessed the SBTI's
perforated detection ability and were included in meta-analysis. Smartphonebased
thermal imaging correctly identified 378 (93.3%; n = 405) perforators,
and computed tomography angiography (CTA) correctly identified 402 (99.2%;
n = 402), although in one study SBTI found additional perforators not detected
on CTA. A random-effects model was used (I2 = 65%), and no significant difference
in perforator detection ability was found between SBTI and CTA( P = 0.27).
Conclusion: This systematic review and meta-analysis supports SBTI as userand
cost-friendly ($229.99), contactless imaging modality with perforator detection
ability comparable to current criterion-standard CTA. Postoperatively, SBTI
outperformed Doppler ultrasound in early detection of microvascular changes
causing flap compromise, allowing for prompt tissue salvage. With a minimal
learning curve, SBTI seems to be a promising method of postoperative flap perfusion
monitoring able to be used by all hospital ranks. Smartphone-based thermal
imaging could thus increase flap monitoring frequency and lower complication
rates, although further study is warranted.

The Utility of Smartphone-Based Thermal Imaging in the Management and Monitoring
of Microvascular Flap Procedures: A Systematic Review and Meta-Analysis

Background
Current measures of vaginoplasty success are adapted from tools validated for use in cisgender women, such as the Female Genital Self-Image Scale (FGSIS) and Female Sexual Function Index (FSFI). There is little research on whether post-operative gender congruence, quality of life (QoL), sexual function, and aesthetic satisfaction are of equal importance for vaginoplasty patients. The survey goal was to examine patient-reported vaginoplasty outcomes related to gender incongruence, post-surgical satisfaction and sexual function.

Methods
Transgender patients receiving surgical care at a single academic center were invited to complete post-surgery surveys. From August 2019 to May 2022, 157 patients who had undergone surgery between September 2016 and March 2022 were contacted. 40 completed consent and post-surgery survey. Questions were selected based on prior literature and FGSIS and FSFI adaptations. Statistical analyses were carried out in RStudio.

Results
Among 40 respondents, mean age was 45.8 years (SD = 14.0) and mean time since surgery was 237.3 days (SD = 260.8). Thirty-two (78.0%) had neovaginoplasty and 9 (22.0%) had genital remodeling without creation of a vaginal opening. Thirty-nine (97.5%) respondents were happier after their operation than they were before. Of the 23 respondents who had engaged in sexual activity in the past month, 10 (43.5%) were often or almost always satisfied with their arousal during sexual activity and 9 (39.1%) were satisfied with their ability to reach orgasm with sexual stimulation. Among this group, 19 (82.6%) felt positively about their genitals, 19 (82.6%) were satisfied with the appearance of their genitals, and 23 (100.0%) were happier after surgery than before. Seventeen respondents (42.5%) did not report sexual activity in the past month. Of these individuals, 15 (88.2%) felt positively about their genitals, 11 (68.8%) were satisfied with the appearance of the genitals and 16 (94.1%) were happier after surgery.

Conclusion
These findings indicate a discordance between the positive psychosocial outcomes of vaginoplasty and post-surgical sexual function. Patient-reported outcomes measures that center sexual function as a primary measure of vaginoplasty success may not accurately capture the QoL benefit afforded by improved gender congruence. While sexual function is important to overall QoL, patients in this study reported high rates of surgical satisfaction and improved happiness regardless of whether they had engaged in sexual activity or were satisfied with their arousal and ability to reach orgasm. More work is needed to develop measures that address the complex relationship between sexual function, sexuality, gender identity, and satisfaction with surgery.

Next from AMA Research Challenge 2023

Analyses of Methanogenic Small Intestine Overgrowth Effects on Growth in Tanzanian Children