Prospective Longitudinal Cohort Study Research Articles

Thriving Beyond Adversity: A Prospective Longitudinal Cohort Study Using a Strength-Based Approach Depicts Indigenous Adolescents with Less Adverse Childhood Experiences (ACEs) Had Fewer Neurodevelopmental Disorders (NDDs)

Improving social and emotional well-being (SEWB) among Indigenous adolescents is crucial. Since neurodevelopmental disorders (NDDs) are common in Indigenous people and adverse childhood experiences (ACEs) are important contributors to negative health outcomes throughout the lifespan, we investigated whether limited ACE exposure is associated with reduced risk of NDDs in Australian Indigenous teens using the data from multiple waves (Wave 1 to Wave 9, and Wave 11) of the Longitudinal Study of Indigenous Children (LSIC). We also examined the role of other protective factors, such as Indigenous cultural identity and school connectedness, against NDDs. A strengths-based approach using mixed-effects logistic regression models examined the protective effect of limited ACE exposure (from LSIC waves 1–9) on NDDs (outcome from LSIC wave 11), adjusting for sociodemographic factors. The NDDs included autism, ADHD, intellectual, neurological, and specific learning disabilities. Of the 370 individuals analysed, 73.2% valued Indigenous cultural identity, and 70.5% were strongly connected at school. More than one-fourth (27.8%) reported limited ACE exposure, while the majority was not diagnosed with NDDs (93%). Longitudinal analysis revealed limited ACE exposure was 6.01 times (95% CI: 1.26–28.61; p = 0.024) more likely to be protective against NDDs compared to those exposed to multiple ACEs. Moreover, valuing cultural identity (aOR = 2.81; 95% CI: 1.06–7.39; p = 0.038) and girls (aOR = 13.88; 95% CI: 3.06–62.84; p = 0.001) were protective against NDDs compared to their respective counterparts. Our findings highlight the need to prevent ACE exposure and promote Indigenous cultural identity in preventing negative health outcomes and the exacerbation of health inequities to strengthen the SEWB of Indigenous communities.

Recurrent peritonsillar abscess in adults: Incidence and risk factors in a prospective longitudinal cohort

ObjectiveThe incidence of recurrent peritonsillar abscess (7.4–22%) was estimated in retrospective studies. The aim of this prospective study was to estimate the cumulative incidence of recurrent peritonsillar abscess and related risk factors. MethodsWe performed a prospective longitudinal cohort study. The study included adult patients (≥18 years old) of both sexes who were attended in the emergency facilities of our tertiary hospital, without peritonsillar abscess background, diagnosed of a first episode of peritonsillar abscess and treated with standard of care (abscess drainage and antibiotics). Patients were followed for 24 months. Cumulative incidence of peritonsillar abscess recurrence was estimated and its 95% confidence interval was calculated; and predictive risk factors were assessed. ResultsBetween January 1st, 2019 and March 9th, 2020, a total of 181 consecutive patients were included. The cumulative incidence of recurrent peritonsillar abscess at 2 years of the diagnosis was 9.9% (18 out of 181, 95% CI: 6.4–15.2%). The only risk factor associated with recurrent peritonsillar abscess in multivariate analysis was low plasma glucose level at the time of emergency room attendance (HR: 0.46, 95% CI: 0.24–0.91, p-value: 0.026). ConclusionPeritonsillar abscess is an incident medical issue, with an established recurrence rate, but with unclear predictive risk factors of recurrence. Further studies are needed to assess the risk factor associated with recurrent peritonsillar abscess.

Enhancement of Family-Centred Care Is Associated with a Reduction in Postmenstrual Age at Discharge in Preterm Infants

Background/Objectives: Long hospitalisation has been recognized as an independent risk factor for poor neurodevelopmental outcomes of preterm infants. Systematic training and early inclusion of parents in their preterm infant’s care is a strategy to shorten the length of hospital stay. We implemented an enhanced stepwise family-centred care program and assessed its effects on postmenstrual age (PMA) at discharge and parental satisfaction. Methods: This prospective single-centre longitudinal cohort study was carried out in a German level III neonatal unit from October 2020 to May 2023. Five consecutive 6-month cohorts (1 baseline and 4 intervention cohorts, 169 infants and their caregivers) were analysed. Results: Mean PMA at discharge did not change in the total cohort but declined significantly in patients without neonatal morbidities from baseline to cohort 4 (37.2 ± 1.4 to 36.1 ± 1.6 weeks; p = 0.036). Concomitantly, discharge with tube feeding raised from 2.4% to 74.1% (p < 0.001) and discharge with home monitoring raised from 9.8% to 74.1% (p < 0.001), while unplanned readmissions remained unchanged (p = 0.44). Parental satisfaction with time point of discharge increased non-significantly from baseline to cohort 4 (75.8% vs. 95.7%; Chi2 0.22). Conclusions: Discharge of preterm infants at a significantly lower PMA is feasible through enhancement of family-centred care and is very well accepted by parents.

Sex-differences in the clinical features, managements and outcomes of early-onset atherosclerotic coronary artery disease in China

Abstract Background/Introduction There is an alarming rise in the incidence of atherosclerotic coronary artery disease (CAD) among young adults, particularly in young women. Sex disparities of early-onset CAD in the context of contemporary cardiovascular practice are not well understood. Purpose We aimed to delineate the differences in clinical profiles and prognosis between young men and women with established early-onset CAD. Methods This is a nationwide, hospital-based, longitudinal prospective cohort study. Young patients (aged ≥18 years and ≤ 45 years) with angiographically confirmed severe atherosclerotic obstructive coronary arteries (luminal narrowing ≥ 70%) were included from 38 hospitals across China between May 2017 and May 2020. Coronary risk factors, clinical features and treatments were compared between men and women at baseline. Participants were followed for 3 years. The outcome was major adverse cardiovascular events (MACE), a composite of cardiovascular death, non-fatal myocardial infarction (MI), unplanned revascularization, and ischemic stroke. The Cox regression analyses were used to estimate hazard ratios (HR) with 95% confidence intervals (CIs) for outcome. Results There were 1524 patients (female: 4.4%) included in this study. The female patients were older than the male patients (41.1±4.0 years for females vs. 39.6±4.4 years for males, p=0.006). They showed a lower prevalence of hypertension, lipid disorders, and smoking or drinking (all p<0.01). The female patients were less likely to have at least 1 modifiable risk factors (female: n=45 (67.2%) vs. male: n=1382 [94.6 %], p<0.001); they showed more favorable laboratory results at baseline, including lipids, serum creatinine and uric acid (all p<0.05) as compared to male patients. Besides, young females presented more often with stable angina on admission, whereas young males tended to present with acute MI (p<0.001). There was no significant sex difference in Gensini Score (p=0.15). Female patients were less likely to undergo revascularization procedures than male patients (73.1% vs. 85.3%, p=0.01). During the 3 years of follow-up, female patients were at a significantly higher risk of MACE compared to their male counterparts (13.4% vs. 5.8%, adjusted HR: 3.07, 95% CI:1.36–6.94, p=0.007) after adjusting for age, smoking, drinking, body mass index, hypertension, diabetes, dyslipidemia, diagnosis and revascularization. Conclusions Distinct sex disparities, unfavorable to young females, were documented among patients with early-onset CAD, with the largest gaps noted in the treatment and prognosis. Despite more favorable baseline profiles, young female patients had insufficient care and 3-fold greater risk for MACE compared to young males. These results highlight the need for strengthening the treatment strategies for this vulnerable disease entity.Figure 1

Association between the cumulative excessive systolic blood pressure and left ventricular mass index

Abstract Background Ambulatory blood pressure (ABP) has been increasingly adopted in day-to-day clinical practices. Although clinicians can access an enormous amount of information regarding an individual’s blood pressures (BPs) through the ABP monitoring (ABPM), to date, only the mean BP is utilized as the diagnostic threshold of hypertension and the therapeutic target for BP control and no other indices were widely used to assess the burdens of high BP in the ABPM. Because elevated systolic BPs (SBPs) cumulatively damage the myocardium and induce hypertrophy and fibrosis, we hypothesized that the summated value of BP readings beyond a target level may be the better indicator of the overall BP loads than the mean BP value. Methods The Korean ABP registry is a multicenter prospective longitudinal cohort study performed in outpatients with hypertension. Among 5,965 patients enrolled in the registry, 951 patients with valid ABPM records and appropriate echocardiography measurements included in the study. The left ventricular mass (LVM) was normalized using the height2.7(m) (LVM index [LVMIH2.7] = LVM/Height2.7). The cumulative excessive SBP CE-SBP) was defined as the summation of the products of excessive SBPs (≥135 mmHg during wake, ≥10 mmHg during sleep) and the durations of the excessive SBP (Figure 1). Results The CE-SBP was non-linearly associated with both the office SBP and the mean SBP, but the association strength was much greater with the mean SBP than with the office SBP (R2=0.902 vs. R2=0.430). In linear regression models, the association of the CE-SBP with the LVMIH2.7 (R2=0.112 [0.074-0.149]) was greater than that of the office SBP (R2=0.072 [0.040-0.103]), the mean SBP (R2=0.082 [0.049-0.116]) or the mean SBP during sleep (R2=0.99 [0.063-0.134]). Non-linear regression models using restrictive cubic spline fits also showed that the association strength was greater with the CE-SBP (R2=0.117 [0.078-0.155]) than with the office SBP, mean SBP or mean SBP during sleep (Figure 2). Left ventricular hypertrophy (LVH) defined as the LVMIH27 ≥54 g/m2.7 was better predicted with the CE-SBP than with the other SBPs. The association between the CE-SBP and LVMIH27 was stronger in the patients not taking antihypertensive medications (R2=0.121) and strongest in those with the non-dipper pattern (R2=0.125). Combination with the variability indices (successive variation and average real variability) during sleep or the maximum SBP during sleep significantly improved the association strength of CE-SBP with LMMIH27, whereas the combination with the mean SBP or the variability indices during the entire period did not, in the linear models. Conclusion The CE-SBP was more strongly associated with the LVMIH27 than the office SBP and the mean SBP in the ABPM. This result suggests that the CE-SBP may be the better indicator of overall BP loads than the office SBP or the mean SBP in the ABPM, in patients with hypertension.Figure 1Figure 2

Differential impact of clinic BP target on the prevalence and predictors of the masked uncontrolled hypertension and white-coat uncontrolled hypertension

Abstract Background Although intensive blood pressure (BP) control have been advocated, major clinical practices guidelines still recommend clinic BP (cBP) < 149/90 mmHg as the target for antihypertensive therapy. But, cBP targets could influence the prevalence and predictors of any hypertension phenotype. We investigated how different cBP targets impacted on the prevalence and predictors of masked uncontrolled hypertension (MUCH) and white-coat uncontrolled hypertension (WUCH) using the Korean Ambulatory Blood Pressure (KorABP) registry. Methods A multicenter prospective longitudinal cohort study was performed in outpatients with hypertension. Among 5,965 patients enrolled in the KorABP registry, 1,601 patients on antihypertensive medications with a valid ambulatory BP monitoring record were included in this study. Two different cBP targets, <130/80mmHg (intensive) and <140/90 mmHg (conventional) were investigated. Results Controlled ambulatory BP (aBP; <130/80 mmHg) was observed in 472 patients (29.5%). Controlled cBP was shown in 348 patients (21.7%) with the intensive cBP target and in 697 patients (43.5%) with the conventional cBP target. Controlled hypertension, WUCH, MUCH and uncontrolled hypertension were found in 294, 174, 54, and 1,075 patients with the intensive target and in 378, 94, 319 and 810 patients with the conventional target, respectively. Among the patients with controlled cBP, the prevalence of MUCH markedly decreased with the intensive target (15.5%), compared to the conventional target (45.8%). In contrast, among the patients with uncontrolled cBP, the prevalence of WUCH had only 3.8% increase with the intensive target (10.4%), compared to the conventional target (14.2%) (Figure 1). With the conventional target, 75.9% of patients with MUCH had cBP between 130/80 mmHg and 139/89 mmHg. The concordance between the controlled aBP and controlled cBP was higher with the intensive target than with the conventional target (Cohen’s κ 0.62 [0.58-0.67] vs. 0.46 [0.41-0.50]). The logistic models for MUCH included the left ventricular mass index and underuse of antihypertensive drugs (<2 types of drugs) as the common predictors of the both targets. With the conventional target, clinic systolic BP and diastolic BP were the strongest predictors of MUCH, but the cBP was not a predictor of MUCH with the intensive target. The logistic models for WUCH included beta-blocker use, increased heart rate and lower waist circumference and clinic systolic BP as the common predictors of WUCH with the both target. The logistic model for MUCH performed better with the conventional target, whereas the logistic model for WUCH performed better with the intensive target (Figure 2). Conclusion The use of the intensive cBP target (<130/80 mmHg) could reduce the prevalence of MUCH with minimal increase in the prevalence of WUCH and would provide the better assessment for the BP control status than the use of the conventional cBP target (<140/90 mmHg).Figure 1Figure 2

Left atrial reservoir strain measured by three-dimensional echocardiography is associated with major adverse cardiovascular events in the general population

Abstract Background Left atrial (LA) strain measured by three-dimensional (3D) echocardiography (3DE) is a novel way of evaluating LA function. The prognostic value of LA strain by 3DE in incident heart failure (HF) and cardiovascular (CV) death has not previously been documented. Purpose We south to investigate whether 3D LA strain measures were associated with incident heart failure (HF) and cardiovascular (CV) death in a population at low risk of CV events. Methods A total of 1,934 participants from a prospective longitudinal cohort study of the general population underwent a comprehensive transthoracic echocardiographic examination including 3DE where LA reservoir strain (LASr), conduit strain (LAScd) and contraction strain (LASct) were quantified. All participants were at sinus-rhythm during 3DE. The endpoint was a composite of HF and CV death. Cox proportional hazards regression was applied. Multivariable adjustments were made for the ARIC-HF risk score (age, gender, heart rate, systolic blood pressure, antihypertensive medication, diabetes, ischemic heart disease, smoking, and body mass index) and left atrial volume index. Results Mean age was 54±17 years, 43% were male. During a median follow-up time of 4.8 years (interquartile range 4.3-5.4 years), 89 participants (4.6%) either developed HF or died of a CV cause. In univariable analysis, LASr and LAScd, but not LASct were significantly associated with the outcome, but after multivariable adjustment only LASr remained significantly associated with outcome (HR 1.04 (95% CI: 1.01-1.08), p=0.016, per 1% decrease) while LAScd and LASct did not. LASr provided incremental prognostic information beyond the ARIC-HF risk score (continuous NRI 0.21±0.11, p=0.027). Compared to participants with a LASr in the 1st tertile (LASr>32%) Participants with an LASr in the in the 3rd tertile (LASr<26.5%) had an almost 7-fold increased risk of HF or CV-death (HR 6.93 (95% CI 3.29-14.58; p=0.001)(Figure). Conclusion LA reservoir strain assessed by 3DE was independently associated with incident HF and CV death, which was not the case for LA conduit and contraction strain. In addition, LA reservoir strain added incremental value beyond clinical risk scores.

Associations Between Physical, Cognitive, and Mental Health Domains of Post-Intensive Care Syndrome and Quality of Life: A Longitudinal Multicenter Cohort Study.

To explore associations between the physical, cognitive, and mental post-intensive care syndrome (PICS) health domains with changes in health-related quality of life (HRQoL) following ICU admission. A longitudinal prospective multicenter cohort study. Patients (n = 4092) from seven Dutch ICUs. None. At ICU admission, 3 and 12 months post-ICU, patients completed validated questionnaires regarding physical health problems, cognitive health problems, mental health problems, and HRQoL. Composite scores were created for the physical health domain (physical problems and fatigue) and mental health domain (anxiety, depression, and post-traumatic stress disorder). Adjusted multivariable linear regression analyses were performed, including covariables (e.g., patient characteristics, disease severity, pre-ICU HRQoL, etc.) to explore associations between the physical, cognitive, and mental health domains of PICS and changes in HRQoL at 3 and 12 months post-ICU. At 3 months (n = 3368), physical health problems (β = -0.04 [95% CI, -0.06 to 0.02]; p < 0.001), cognitive health problems (β = -0.05 [95% CI, -0.09 to -0.02]; p < 0.001), and mental health problems (β = -0.08 [95% CI, -0.10 to -0.05]; p < 0.001) were negatively associated with changes in HRQoL. Also, at 12 months (n = 2950), physical health problems (β = -0.06 [95% CI, -0.08 to -0.03]; p < 0.001), cognitive health problems (β = -0.04 [95% CI, -0.08 to -0.01]; p < 0.015), and mental health problems (β = -0.06 [95% CI, -0.08 to -0.03]; p < 0.001) were negatively associated with changes in HRQoL. PICS symptoms in the physical, cognitive, and mental domains are all negatively associated with changes in HRQoL at 3 and 12 months post-ICU. At 3 months, PICS symptoms in the mental domain seem to have the largest negative associations. At 12 months, the associations of PICS in the mental and physical domains are the same. This implies that daily ICU care and follow-up care should focus on preventing and mitigating health problems across all three PICS domains to prevent a decrease in HRQoL.

Short- and medium-term longitudinal outcomes of children diagnosed with multisystem inflammatory syndrome in children - report from a single centre in Pakistan.

To determine the short- and medium-term cardiac outcomes in children admitted with multisystem inflammatory syndrome in children at a tertiary care centre in Pakistan. Children fulfilling the criteria for multisystem inflammatory syndrome and admitted to the hospital between April 2020 and March 2022 were enrolled in this prospective longitudinal cohort study. From admission to discharge, laboratory and cardiac parameters were recorded for all patients, who were subsequently followed up in clinics at various intervals. Data analysis was conducted using STATA version 15.0. A total of 51 children were included, with viral myocarditis (41.2%) and toxic shock syndrome (33.3%) being the most common phenotypes. The cardiovascular system was most commonly affected in 27 children (53%) with laboratory evidence of inflammation and myocardial injury with median and interquartile levels of ferritin 1169 (534-1704), C-reactive protein 83 (24-175), lactate dehydrogenase 468 (365-1270), N-terminal pro-B-type natriuretic peptide 8,656 (2,538-31,166), and troponin 0.16 (0.02-2.0).On admission, decreased left ventricular ejection fraction was observed in 58.8% of patients and impaired global longitudinal strain in 33.3%. At discharge, left ventricular ejection fraction had normalised in 83% of patients. Pericardial effusion resolved in all patients, and valvulitis resolved in 86% by 12 months. Paediatric ICU admission was required in 42 (82%) of patients with an overall mortality of 12% (n = 6). Our study finds high hospital mortality for multisystem inflammatory syndrome in children compared to 1-2% from previous studies. Yet, in Pakistan, surviving children with multisystem inflammatory syndrome show favourable short- to medium-term cardiac outcomes.

Navigating ethical and legal challenges in the HEALthy Brain and Child Development Study: Lessons learned from the ethics, law, policy working group

The HEALthy Brain and Child Development (HBCD) Study, a multi-site prospective longitudinal cohort study, will examine human brain, cognitive, behavioral, social, and emotional development beginning prenatally and planned through early childhood. The HBCD study has faced several ethical and legal challenges due to its goal of enrolling pregnant people (including those with substance use disorder) and their newborns. Challenges not fully anticipated at the outset emerged from the rapidly changing legal landscape around reproductive rights in the United States. By embedding scholars in bioethics and law within research teams and engaging them in conversation with each other and other study personnel, we were able to address many challenges proactively and respond promptly to unanticipated challenges. In this paper, we highlight several important ethical and legal challenges that arose from the first phase of funding through the beginning of participant enrollment. We explain the methods used to address these challenges, the ethical and legal tradeoffs that arose, and the resolution of challenges through the design of the study. Based on this experience, we provide recommendations for research teams, sponsors, and reviewers to address legal risks and promote the ethical conduct of studies with pregnant people and caregivers. We highlight the importance of collaboration with bioethics and legal scholars in studies involving complex and evolving legal risks, as well as the necessity of designing robust approaches to informed consent and maintaining participant trust while navigating ethical challenges in research.

Chemotherapy-induced cognitive impairment and its long-term development in patients with breast cancer: results from the observational CICARO study.

Chemotherapy-induced cognitive impairment (CICI) is a well-recognized side effect of breast cancer treatment. However, prospective long-term evaluations of CICI using standardized neuropsychological tests are scarce. This prospective longitudinal cohort study investigated cognitive dysfunction and its impact on quality of life and everyday functioning in patients with breast cancer receiving first-line chemotherapy compared to patients with breast cancer without chemotherapy. Assessment occurred prior to chemotherapy, postchemotherapy (median 6 months), and 2-3 years later. We used standardized neuropsychological tests, questionnaires, and scales to assess patients' quality of life and functioning. Additionally, serum analysis for neurodegenerative markers and autoantibodies was conducted. We included n = 53 patients. Overall cognitive function declined statistically significantly (P = .046) postchemotherapy compared to control patients, mostly driven by a reduced figural memory (P = .011). Patients who received chemotherapy showed a greater reduction in quality of life (increased fatigue symptoms, P = .023; reduced Karnofsky index, P<.001); however, without a statistically significant effect on cognitive decline. The neurodegenerative markers Neurofilament light chain (NfL) and phosphorylated Neurofilament heavy chain (pNfH) increased statistically significantly (P<.001) postchemotherapy and pNfH correlated with overall cognitive function. After 2-3 years, both cognitive performance and quality of life were comparable between chemotherapy-treated and control patients. Our findings suggest that chemotherapy statistically significantly contributes to overall cognitive dysfunction in patients with breast cancer, which disappears after 2-3 years, indicating a recovery in both objectively measurable cognitive function and subjective quality of life. Future research should examine larger sample sizes and explore screening indicators, particularly pNfH.

Towards accurate screening and prevention for PTSD (2-ASAP): protocol of a longitudinal prospective cohort study

BackgroundEffective preventive interventions for PTSD rely on early identification of individuals at risk for developing PTSD. To establish early post-trauma who are at risk, there is a need for accurate prognostic risk screening instruments for PTSD that can be widely implemented in recently trauma-exposed adults. Achieving such accuracy and generalizability requires external validation of machine learning classification models. The current 2-ASAP cohort study will perform external validation on both full and minimal feature sets of supervised machine learning classification models assessing individual risk to follow an adverse PTSD symptom trajectory over the course of 1 year. We will derive these models from the TraumaTIPS cohort, separately for men and women.MethodThe 2-ASAP longitudinal cohort will include N = 863 adults (N = 436 females, N = 427 males) who were recently exposed to acute civilian trauma. We will include civilian victims of accidents, crime and calamities at Victim Support Netherlands; and who were presented for medical evaluation of (suspected) traumatic injuries by emergency transportation to the emergency department. The baseline assessment within 2 months post-trauma will include self-report questionnaires on demographic, medical and traumatic event characteristics; potential risk and protective factors for PTSD; PTSD symptom severity and other adverse outcomes; and current best-practice PTSD screening instruments. Participants will be followed at 3, 6, 9, and 12 months post-trauma, assessing PTSD symptom severity and other adverse outcomes via self-report questionnaires.DiscussionThe ultimate goal of our study is to improve accurate screening and prevention for PTSD in recently trauma-exposed civilians. To enable future large-scale implementation, we will use self-report data to inform the prognostic models; and we will derive a minimal feature set of the classification models. This can be transformed into a short online screening instrument that is user-friendly for recently trauma-exposed adults to fill in. The eventual short online screening instrument will classify early post-trauma which adults are at risk for developing PTSD. Those at risk can be targeted and may subsequently benefit from preventive interventions, aiming to reduce PTSD and relatedly improve psychological, functional and economic outcomes.

One-Year Surveillance of a Patient Cohort’s Lung Ultrasonography Findings Post Mild-Moderate COVID-19 Infection

Objective: Lung involvement due to COVID-19 infection relates to patient clinical outcomes. However, little evidence exists on whether an abnormal lung sonogram, during an initial outpatient infection, may signal an abnormal immunologic response and lasting abnormalities. The aim of this study was to observe whether high-risk outpatients, previously infected with SARS CoV-2 and found to have an initial abnormal lung sonogram, had persistent diagnostic findings at a 1-year re-examination. Materials and Methods: A prospective longitudinal cohort study was performed, based on a prior study completed in January 2022 wherein 55/201 (27%) of consecutive outpatients infected with SARS-CoV-2 received therapy at an outpatient monoclonal antibody clinic and had presented with an abnormal lung ultrasound containing at least 3 apical lung B-line artifacts (LUS+). One year later, the original 55 LUS+ patients were contacted for re-examination; as a result, 14 LUS+ patients consented to a repeat LUS tospecifically recheck the apical area of the lungs for persistent B-line artifacts. The same ultrasound equipment system and imaging methodology were used for this cohort of patients. Additional data was collected regarding COVID-19 test-positive re-infection, persistent pulmonary symptoms during the past year, and COVID-19 vaccination status. Results: Of the 14 LUS+ patients, the mean cohort age was 63 ± 9 years, of which 71% were men. Over the ensuing year, 43% had persistent symptoms, 71% had updated vaccination, and 36% had a self-reported re-infection. The re-infection was reported to have occurred a median of 7 months after the initial infection. The cohort was sub-divided into those with persistent LUS+ compared to those that reverted to a normal scan. The mean age was 69 ± 10 years among those LUS+ compared to 56 ± 8 years in the normalized group. The body mass index (BMI) was 32 kg/m2 in those LUS+ compared to 27 kg/m2 in the normalized group. The cohort has 6 men and 2 women in the LUS+ group compared to 4 men and 2 women in the normalized group. One LUS+ patient out of eight reportedly had been reinfected compared to four normalized patients out of six stated being reinfected. Three LUS+ patients out of eight reported having persistent symptoms compared to three normalized patients out of six complaining of continued COVID-19 symptoms. Conclusion: Based on the 1-year repeated LUS, for this cohort, there was a high prevalence of persistent symptoms and lung abnormalities, in those who had mild-moderate outpatient COVID-19 and received monoclonal antibody therapy. The longitudinal data collection on this cohort of COVID-19 positive outpatients may suggest that individual immune responses or viral virulence factors may play a role in B-line persistence. Certainly, future LUS results may be confounded by a previous COVID-19 infection.

Fact or Fiction-Accelerometry Versus Self-Report in Adherence to Pediatric Concussion Protocols: Prospective Longitudinal Cohort Study.

Concussion, or mild traumatic brain injury, is a growing public health concern, affecting approximately 1.2% of the population annually. Among children aged 1-17 years, concussion had the highest weighted prevalence compared to other injury types, highlighting the importance of addressing this issue among the youth population. This study aimed to assess adherence to Return to Activity (RTA) protocols among youth with concussion and to determine if better adherence affected time to recovery and the rate of reinjury. Children and youth (N=139) aged 5-18 years with concussion were recruited. Self-reported symptoms and protocol stage of recovery were monitored every 48 hours until symptom resolution was achieved. Daily accelerometry was assessed with the ActiGraph. Data were collected to evaluate adherence to the RTA protocol based on physical activity cutoff points corresponding to RTA stages. Participants were evaluated using a battery of physical, cognitive, and behavioral measures at recruitment, upon symptom resolution, and 3 months post symptom resolution. For RTA stage 1, a total of 13% of participants were adherent based on accelerometry, whereas 11% and 34% of participants were adherent for stage 2 and 3, respectively. The median time to symptom resolution was 13 days for participants who were subjectively reported adherent to the RTA protocol and 20 days for those who were subjectively reported as nonadherent (P=.03). No significant agreement was found between self-report of adherence and objective actigraphy adherence to the RTA protocol as well as to other clinical outcomes, such as depression, quality of life, and balance. The rate of reinjury among the entire cohort was 2% (n=3). Overall, adherence to staged protocols post concussion was minimal when assessed with accelerometers, but adherence was higher by self-report. More physical activity restrictions, as specified in the RTA protocol, resulted in lower adherence. Although objective adherence was low, reinjury rate was lower than expected, suggesting a protective effect of being monitored and increased youth awareness of protocols. The results of this study support the move to less restrictive protocols and earlier resumption of daily activities that have since been implemented in more recent protocols.

Effect of Adopting a Gluten-Free Diet on Exposure to Arsenic and Other Heavy Metals in Children With Celiac Disease: A Prospective Cohort Study.

Lifelong adherence to a gluten-free diet (GFD) is the primary treatment of celiac disease (CeD), a gluten-driven enteropathy. Concerns have been raised about increased exposure to arsenic from a GFD because rice, which naturally bioaccumulates arsenic, is commonly used as a substitute for gluten-containing grains such as wheat. We hypothesize that arsenic exposure increases in newly diagnosed children with CeD after they adopt a GFD. This is a single-center prospective longitudinal cohort study of children (age 2-18 years) with elevated celiac serology who underwent a diagnostic endoscopy before initiation of a GFD between January and May 2022. The primary outcome was change in urinary arsenic concentration between endoscopy and after 6 months on a GFD. Of the 67 recruited participants, 50 had a biopsy diagnostic of CeD and were invited to continue the study. Thirty-five participants completed sample collection. Participants were from a middle-class, well-educated population that was predominantly White with presenting symptoms of abdominal pain (51%) and diarrhea (29%). After 6 months on a GFD, there was a significant increase in the median urinary arsenic concentration (3.3 µg/L vs 13.6 µg/L, P = 0.000004). In regression models, family history of CeD and Hispanic ethnicity were associated with having a higher urinary arsenic concentration after 6 months on a GFD. Children with newly diagnosed CeD have increased arsenic exposure shortly after transitioning to a GFD. While the arsenic levels were well below acutely toxic concentrations, the clinical impact of chronic exposure to mildly elevated arsenic levels is unknown.

Association between willingness to exercise and incident disability in older adults: a prospective longitudinal cohort study.

To investigate whether the willingness to exercise (WTE) and exercise habits affect the incidence of disability among older adults. This study included 8,354 individuals (72.5 ± 6.2years, 55.9% female). The participants were divided into three categories based on their WTE: unwillingness to exercise, willingness to exercise (but without exercise habits), and exercise habits. The incidence of disability was prospectively determined within 24months of the follow-up. Cox regression analysis was used to examine the relationship between WTE and the incidence of disability. Overall, 600 (7.2%), 4,703 (56.3%), and 3,051 (36.5%) participants were classified as unwillingness to exercise, willingness to exercise, and exercise habits, respectively. Compared with the unwillingness to exercise group, the willingness to exercise group (hazard ratio [HR] 0.71, 95%Confidence Interval [CI] 0.52-0.96) and the exercise habits group (HR 0.65, 95%CI 0.46-0.92) had a lower risk of disability incidence. These results suggest that WTE reduces the risk of disability in older adults. Therefore, the importance of increasing WTE to prevent the occurrence of disabilities is clear. Our results suggest that even though physical activity declines with age, it is important to have the desire to exercise and develop exercise habits.

7303 Fasting and Post-load Glucose in Exclusively Breastfeeding Women With Diabetes Risk Factors

Abstract Disclosure: N. Neamonitaki: None. T. Thaweethai: None. D. Pant: None. K. James: None. M.D. Soffer: None. E.A. Rosenberg: None. C.E. Powe: Consulting Fee; Self; Mediflix, Inc. Other; Self; Wolters Kluwer, Up to Date Author. Background: Epidemiologic studies show a reduction in type 2 diabetes incidence with increased lactation duration and intensity, but physiologic mechanisms underlying this association are incompletely characterized. We examined associations between lactation and glycemic physiology in postpartum women. ​ Methods: We conducted a secondary analysis of postpartum participants in a prospective longitudinal cohort study that examined glucose and insulin physiology via serial 2-hr 75-gram oral glucose tolerance tests during pregnancy and postpartum in women with diabetes risk factors. We used linear regression to examine associations between exclusive breastfeeding and fasting glucose, adjusting for age, race/ethnicity, education, body mass index, and number of weeks postpartum. Secondary analyses examined associations with post-load glucose and insulin physiology. Additional analyses considered exclusive breastfeeding compared to exclusive formula feeding and a combination of formula and breastfeeding separately using a categorical exposure variable. Results: Of N=108 women at a mean (SD) of 11 (5.0) weeks postpartum, 56 reported exclusively breastfeeding and 52 reported not exclusively breastfeeding (15 were exclusively formula feeding and 37 were both breast- and formula feeding). Mean (SD) fasting glucose was 83 (7.0) mg/dl in those exclusively breastfeeding and 85 (8.9) mg/dl in those who were not. Fasting glucose was not significantly different in those who were exclusively breastfeeding compared to those who were not after confounder adjustment (β [95% CI] =-1.3 [-4.6, 2.0] mg/dl, P=0.45). The 60- minute post-load glucose was nominally higher in those exclusively breastfeeding, with a mean (SD) of 132 (37.5) mg/dl versus 118 (31.6) mg/dl in those who were not; this difference did not reach statistical significance in the adjusted model (β [95% CI] =12.6 [-2.1, 27] mg/dl, P=0.09). In additional analyses, fasting glucose was not significantly different between women exclusively breastfeeding, exclusively formula feeding, or both breast- and formula feeding; however, post-load glucose at 30 and 60 minutes was higher in the exclusively breastfeeding group compared to the exclusively formula feeding group (30-minute: β [95% CI]= 16 [0.36,32] mg/dl, P=0.045); 60-minute: 26 [4.0,47] mg/dl, P=0.02) in adjusted models. We did not find significant associations with insulin physiology measures. Conclusion: We did not observe lower fasting glucose with exclusive breastfeeding. Instead, glucose levels at 30 and 60 minutes after an oral glucose load were higher in exclusively breastfeeding participants compared to exclusively formula feeding participants. Presentation: 6/2/2024

7829 Hydrocortisone Vs Prednisone During Recovery Following Surgical Cure For Endogenous Hypercortisolism: A Longitudinal Observational Study

Abstract Disclosure: R. Sandooja: None. J. Saini: None. R. Gregg garcia: None. C. Zhang: None. S. Achenbach: None. E. Atkinson: None. J. Van Gompel: None. W.F. Young: None. I. Bancos: None. Hydrocortisone vs Prednisone During Recovery Following Surgical Cure for Endogenous Hypercortisolism: A Longitudinal Observational Study Introduction: Glucocorticoid withdrawal syndrome (GWS) is a constellation of symptoms that occurs after successful surgery for endogenous hypercortisolism. The objective of this study is to compare hydrocortisone versus prednisone on GWS symptoms. Methods: Study design: Single-center prospective longitudinal cohort study, 2019-2023. Participants: Adults with Cushing syndrome (CS) and mild autonomous cortisol secretion (MACS) with post-operative adrenal insufficiency treated with either hydrocortisone or prednisone for glucocorticoid replacement. Measurements: Clinical and biochemical severity scores for hypercortisolism were calculated. Quality of life (QOL) was assessed using Short Form-36 (SF-36) and Cushing QOL surveys. GWS was assessed using weekly AddiQoL surveys for the first 12 weeks after surgery. Results: Of 131 patients, 91 (69%) patients were treated with hydrocortisone and 40 (31%) with prednisone. No differences in age (median age 51 vs 53 years, P=0.62), sex (84 vs 85% women, P=0.83), etiology of hypercortisolism (ACTH-dependent: 44% vs 48%, P=0.26), clinical severity of hypercortisolism (median score 13 vs 12, P=0.97), or biochemical severity of hypercortisolism (median score of 6 in both, P=0.31) were noted between groups. When assessed at 4-, 8-, and 12-weeks post-surgery, the prevalence and trajectory of symptoms (fatigue, myalgias/arthralgias, sleep, headaches, nausea, weakness) were similar in patients treated with hydrocortisone and prednisone (P&amp;gt;0.05 for all). However, patients treated with prednisone were less likely to report mood changes (8.5% vs 20.9%, P= 0.004) compared to those treated with hydrocortisone. When compared to the presurgical baseline, the overall Cushing QOL score 12 weeks post-surgery improved in both groups (mean delta 8.9 vs 13.0, P=0.21). No differences in the hydrocortisone vs prednisone treatment were found in the SF-36 physical component score (mean delta of -1.7 vs 0.3, P=0.23) and SF-36 mental component score (mean delta 2.3 vs 5.0, P=0.22). Using multivariable analysis, age (estimate 0.22, P= 0.005), clinical severity score (estimate -0.73, P&amp;lt;0.001), female sex (estimate -5.45, P= 0.046) but not glucocorticoid type (estimate -0.06, P=0.98) were associated with the overall GWS symptom burden at 12 weeks. Conclusion: Use of prednisone after curative surgery for hypercortisolism was associated with lower mood symptoms, but did not impact the overall severity or trajectory of other symptoms associated with GWS. Baseline clinical severity of hypercortisolism, age, and female sex were associated with GWS burden. Presentation: 6/1/2024

Associations of inflammation related prenatal adversities with neurodevelopment of offspring in one year: a longitudinal prospective birth cohort study

BackgroundThe recent Maternal Immune Activation (MIA) theory suggests maternal systemic inflammation may serve as a mediator in associations between prenatal maternal adversities and neurodevelopmental diseases in offspring. Given the co-exposure to multiple adversities may be experienced by pregnant person, it is unclear whether a quantitative index can be developed to characterize the inflammation related exposure level, and whether this index is associated with neurodevelopmental delays in offspring.MethodsBased on Jiangsu Birth Cohort (JBC), a total of 3051 infants were included in the analysis. Inflammation related Prenatal Adversity Index (IPAI) was constructed using maternal data. Neurodevelopmental outcomes were assessed using the Bayley Scales of Infant and Toddler Development, third edition, screening test in one year. Multivariate linear regression and Poisson regression model were performed to analyze the associations between IPAI and neurodevelopment in offspring.ResultsCompared with “low IPAI” group, offspring with “high IPAI” have lower scores of cognition, receptive communication, expressive communication, and fine motor. The adjusted β were − 0.23 (95%CI: -0.42, -0.04), -0.47 (95%CI: -0.66, -0.28), -0.30 (95%CI: -0.49, -0.11), and − 0.20 (95%CI: -0.33, -0.06). Additionally, the elevated risk for noncompetent development of cognition and receptive communication among “high IPAI” group was observed. The relative risk [RR] and 95% confidence interval [CI] were 1.35 (1.01, 1.69) and 1.37 (1.09, 1.72).ConclusionsOur results revealed a significant association between higher IPAI and lower scores across cognition, receptive communication, expressive communication, and fine motor domains, and an increased risk of noncompetent development in the cognition and receptive communication domains.

Impact of protraction or orthognathic surgery for class III malocclusion on longitudinal quality of life in patients with cleft lip and palate.

This study assessed overall quality of life (QoL) over time in youth with cleft lip and palate (CLP) undergoing maxillary protraction treatment or orthognathic surgery for class III malocclusion to identify any differences in QoL based on treatment group and outcome success. A prospective longitudinal cohort study was conducted in two pediatric hospitals. The Short Form Health Survey (SF-12) measured physical and mental QoL prior to treatment, at maximal correction, at treatment completion, and at 1-year post treatment. Analyses included one-sample, two-sample, and paired t-tests and analyses of variance and covariance. Participants (N = 91) either completed protraction (n = 53) at age 11-14 or surgery (n = 38) at age 16-21. Participants were mostly Latinx (67%) males (55%) born with unilateral CLP (81%) and there were no demographic differences between the two groups other than age. The total sample's QoL was in the average range and significantly higher than national norms. No significant differences were found in QoL-based outcome success; however, the protraction group showed a gradual physical QoL improvement over time, while the surgery group experienced a temporary drop in physical QoL postoperatively. At treatment completion, higher physical QoL was associated with higher socioeconomic status. At a year post treatment, mental QoL was significantly higher for males. Both protraction and surgery appear to be acceptable treatment options in terms of overall QoL for youth with CLP. While treatment success did not impact QoL, there were some differences in physical QoL coinciding with the treatment phase as well as individual factors.