Prospective Longitudinal Studies Research Articles

Longitudinal evaluation of hemodynamic blood and echocardiographic biomarkers for the prediction of BPD and BPD-related pulmonary hypertension in very-low-birth-weight preterm infants

Very-low-birth-weight infants (VLBW, < 1500 g) are at risk of developing bronchopulmonary dysplasia (BPD) and are at risk for BPD-related pulmonary hypertension (PH). The longitudinal measurement of innovative blood and echocardiographic biomarkers might allow for a risk stratification of these infants. A prospective single-center cohort study was conducted between 01/2021 and 06/2023. Inclusion criteria were the combination of a birth weight < 1500 g and a gestational age (GA) ≤ 30/0 weeks. Assessment timepoints: T1 (day 7), T2 (day 28), and T3 (at 36 weeks post-menstrual age, PMA). Overall, 71 preterm infants were included for final analysis. The Zlog-transformed NTproBNPZlog (at T1 AUC 0.772; p = 0.019; at T2 AUC 0.874, p = 0.002), and endothelin-1 (ET1, at T1 AUC 0.789, p = 0.013) were identified as an early predictive biomarker for BPD/death in the univariate analysis. Additionally, echocardiographic markers of ventricular function and PH at T1 were predictive for BPD/death in the univariate analysis, with the highest predictivity found for the tricuspid annular plane systolic excursion-TAPSE (AUC 0.748, p = 0.016) and the pulmonary artery acceleration time to right ventricular ejection time (PAAT/RVET; AUC 0.744, p = 0.043). Regarding predictability of mortality alone NTroBNPZlog (at T1 AUC 0.973, p = 0.000), and CA125 (at T1 AUC 0.747, p = 0.008) were identified as potential predictors, as well as TAPSE (AUC 0.926, p = 0.000), and PAAT/RVET (AUC 0.985, p = 0.000) Several biomarkers including ET-1 (at T1 AUC 0.893, p = 0.000), TAPSE (AUC 0.974, p = 0.000), and PAAT/RVET (AUC 1.0, p = 0.000) at T1 were identified as univariate predictors for BPD-PH. In the multivariate analysis, no biomarker was identified as an independent predictor of the primary endpoint. Conclusion: Mainly at an early stage of postnatal neonatal care in VLBW preterm infants, several biomarkers were found to be associated with the combined endpoint BPD/death and BPD-PH. New candidates of blood biomarkers (NTproBNPZlog, ET-1, and CA125) and echocardiographic markers (TAPSE, PAAT/RVET) might serve as innovative predictors for BPD, BPD-PH, and adverse outcomes in VBLW infants. What is Known:• VLBW infants are at risk for the development of BPD and BPD-related PH, which both are main contributors for short and long-term morbidity and mortality. Several studies in the past focused on the evaluation of circulating blood biomarkers and biomarkers from echocardiographic assessment of these infants. But to date, there is still a lack on longitudinal prospective studies especially in VLBW infants.What is New:• For the first time, this set of selected blood biomarkers (with the first description of Zlog-transformed NTproBNP and CA125 in preterm infants) and several echocardiographic markers were analyzed in a prospective longitudinal study from birth until 36 weeks post menstrual age in VLBW infants. Our data help clinicians to identify preterm infants at risk for BPD, BPD-PH and death and to offer new candidates of biomarkers. This might help to facilitate decision making and guidance of therapy in these highly vulnerable patients.

Fractures in the Transgender Population: A Retrospective Study

Introduction. While data on the bone health of transgender individuals exist, less is known about related fractures. The authors aimed to compare the anatomic locations of and impact of co-morbidities on fractures between transgender and cisgender populations at a single institution. Methods. The authors conducted a retrospective chart review of patients with fractures at a single institution between January 2020 and January 2021. Demographics, fracture locations, and comorbidities were identified and compared between cisgender and transgender individuals. Statistical analyses included χ2 or Fisher exact tests for proportions and independent t-tests or Wilcoxon rank-sum tests for continuous measures. Results. Transgender patients, compared to cisgender patients, were younger (W=258823, p&lt;0.001) and had a higher incidence of shoulder/upper arm fractures (10/26 [38%] vs 1,847/12,463 [15%], p=0.003) but no lumbar spine fractures. There were no other significant differences in fracture locations. The transgender group had a higher prevalence of depression (14/26 [54%] vs 2,696/12,463 [22%], p&lt;0.001), while hypertension was more common in the cisgender population (6,211/12,463 [50%] vs 5/26 [19%], p=0.003). While most fractures in the transgender group were not due to high-energy trauma, none of the individuals had a history of bone mineral density disorders. Conclusions. Our findings show that there were no significant differences in fracture locations between transgender and cisgender patients, except at one site. Larger studies, including longitudinal prospective studies, are needed to better understand bone health and fracture risk among transgender patients, particularly regarding changes over time with gender-affirming treatment.

Efficacy and Safety of Lithium for Suicide and Suicide-Related Behaviors in Youth: A Review of the Literature.

This systematic review evaluates the anti-suicidal properties of Lithium in children and adolescents with Bipolar Disorder (BD), addressing gaps in evidence regarding its efficacy and safety in reducing suicidality and self-harming behaviors. A comprehensive literature search was conducted across PubMed, Web of Science, and Scopus up to February 2024. Eligible studies were those focusing on patients aged 25 years or younger, examining Lithium therapy and its impact on suicidal ideation and behaviors. The review included randomized controlled trials, longitudinal prospective and retrospective studies, and cross-sectional studies, while excluding expert opinions and case reports. Evidence generally supports the efficacy of Lithium in reducing suicidal ideation and self-harming behaviors in youth with BD, though results are mixed. Randomized controlled trials demonstrated its effectiveness in mitigating suicidal thoughts during acute manic episodes, with effects persisting post-treatment. Longitudinal studies suggested that Lithium might offer superior outcomes compared to other mood stabilizers, although its specific impact on suicidality remains inconclusive. Cross-sectional studies and retrospective analyses reveal associations between Lithium use and reduced self-harming behaviors, but causality remains uncertain. While mood-stabilizing effects of Lithium offer potential benefits for reducing suicidality in youth, evidence on its direct impact on emotional dysregulation (ED) and long-term efficacy is limited. Variability in individual responses and adherence issues underscore the need for further research. Future studies should include larger, diverse samples, focus on ED symptoms, and explore Lithium mechanisms in suicidality prevention. Lithium remains a promising treatment for mood stabilization and reduction in suicidality in youth with BD.

Examination of optical coherence tomography findings in patients with pregabalin use disorder.

Pregabalin abuse is a rapidly growing health problem worldwide, and little is known about the effects of prolonged high-dose use in patients with pregabalin use disorder. In this study, the effects of pregabalin abuse on retinal layers were investigated in patients with pregabalin use disorder (PGUD). This study included 35 controls and 34 patients with PGUD, according to Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 criteria. Optic coherence tomography (OCT) measurements including the retinal nerve fiber layer (RNFL), ganglion cell layer-inner plexiform layer (GCL-IPL) and ganglion cell complex (GCC) were performed. RNFL thickness was evaluated in four quadrants (inferior, superior, nasal, temporal). GCL-IPL and GCC thickness were evaluated in six sectors (superior, superonasal, inferonasal, inferior, inferotemporal, superotemporal). GCC inferonasal (p = 0.040, r = 0.354), GCC inferior (p = 0.018, r = 0.402) GCL-IPL inferior (p = 0.031, r = 0.370) and GCL-IPL inferotemporal (p = 0.029, r = 0.376) thickness were positively correlated with the duration of pregabalin use. There was no significant sector or quadrant-wise difference between groups (p > 0.05). Our findings emphasized the drug's potential neuroprotective effect. It should be taken into consideration that neurodegenerative changes due to substance use disorder occur with long-term. Longitudinal prospective studies investigating dose-duration relationship are needed.

The relationship between the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet and metabolic health status in adolescents with overweight and obesity: results from a cross-sectional study in Iran.

Few studies investigated the association between Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet and metabolic health status, particularly among adolescents. The present study was designed to investigate the association of MIND diet with metabolic health status in Iranian adolescents with overweight/obesity. This cross-sectional study was done among 203 adolescents with overweight/obesity (12-18 years) in Isfahan, Iran. A validated FFQ was applied to collect dietary intakes. Anthropometric indices and blood pressure were also measured by standard procedures. Fasting blood samples were obtained to determine serum insulin, glucose and lipid profile. To categorise participants as being with metabolically healthy overweight/obesity (MHO) or metabolically unhealthy overweight/obesity (MUO), two methods including International Diabetes Federation (IDF) criteria and IDF plus Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) were applied. Participants had a mean age of 13·98 years and 50·2 % of them were girls. In fully adjusted models, participants with highest MIND diet adherence had lower odds of MUO status based on IDF (OR = 0·20; 95 % CI 0·08, 0·51) and IDF/HOMA-IR (OR = 0·22; 95 % CI 0·08, 0·59) criteria. Stratified analyses revealed that this association was stronger among girls and was only significant among individuals with overweight. An inverse association was also found between MIND diet score and odds of hyperglycaemia and insulin resistance (IR). Higher MIND diet adherence was associated with lower odds MUO in adolescents with overweight/obesity. Inverse associations were also found between MIND diet and odds of hyperglycaemia and IR. Future longitudinal prospective studies are necessary to confirm our results.

Circulating thrombospondin 2 as a predictor of hepatocellular carcinoma in hepatitis B patients undergoing nucleos(t)ide analog therapy

Thrombospondin 2 (TSP2) plays a vital role in collagen/fibrin formation, bone growth, vascular density regulation, hemostasis, and cell adhesion. Close associations of serum TSP2 with histological severity in non-alcoholic fatty liver disease and chronic hepatitis C were reported. The present study investigated the significance of circulating TSP2 in chronic hepatitis B patients. Eighty-seven biopsy-proven chronic hepatitis B patients were analyzed in cross-sectional Study 1 to search for correlations between serum TSP2 levels prior to liver biopsy and clinicopathological parameters. In longitudinal Study 2, 51 chronic hepatitis B patients with long-term follow-up (mean: 7.5 years) were examined for changes in serum TSP2 levels during nucleos(t)ide analog (NA) therapy along with trends in hepatocarciongenesis. In Study 1, serum TSP2 levels were not significantly associated with portal inflammation or fibrosis. Study 2 revealed that serum TSP2 was significantly decreased after 48 weeks of NA therapy (P < 0.001). Notably, TSP2 levels at 48 weeks of NA administration (TSP2-48W) were significantly higher in the hepatocellular carcinoma (HCC) (+) group than in the HCC (−) group (P = 0.043). Kaplan–Meier analysis showed that higher TSP2-48W (≥ 24 ng/mL) was associated with future HCC development (P = 0.030). Serum TSP2 levels may be a potential predictor of HCC development in hepatitis B patients receiving NA therapy. Longitudinal prospective studies are necessary to validate our findings.

Standardized Temporary Atrial Epicardial Wire Locations Lead to Enhanced Atrial Signal Identification.

Background: Arrhythmias, common after pediatric cardiac surgery, are associated with increased morbidity and mortality. Atrial epicardial wires (AEW) improve diagnostic accuracy but have variable pacing and sensing properties based on their location. Even so, there are no longitudinal prospective pediatric studies examining ideal placement of AEW. Methods: This multicenter study compared atrial amplitudes, pacing sensitivities and thresholds via AEW placed at Bachmann's Bundle (BB) and the interatrial groove near the right pulmonary veins (IGRPV) versus the surgeons' standard locations. An AtriAmp system was used to obtain an atrial ECG to calculate atrial and ventricular amplitude from atrial electrograms on the bedside monitor. Sensitivities and thresholds via a temporary pacemaker were documented. ANOVA tests with repeated measures and post-hoc pairwise comparisons were performed to compare variables within the first 24-h postoperative hours. Mixed effects linear regression models were employed to examine daily trends. Results: In the first 24-h following cardiac surgery, AEW at BB and IGRPV showed significantly larger atrial amplitudes than the surgeons' standard locations. In addition, there was a negative trend in atrial ECG amplitude in all AEW from postoperative days 0 to 1; however, subsequent days showed a positive mean change in atrial amplitude with largest increase seen at BB. Atrial sensing as measured by the temporary pacemaker had statistically greater atrial signal amplitude from the BB-IGRPV set in both polarities (ie, with the BB as the - or + electrode pair) as compared to the surgeons' standard locations. No difference in atrial thresholds (mA) were noted in the immediate postoperative period or over time, with a relatively low atrial threshold at all sites. Conclusion: Standardization of AEW at Bachmann's Bundle can yield largest atrial amplitudes by atrial ECG and highest atrial sensing parameters without compromising atrial thresholds.

Environment and systemic autoimmune rheumatic diseases: an overview and future directions.

Despite progress in our understanding of disease pathogenesis for systemic autoimmune rheumatic diseases (SARD), these diseases are still associated with high morbidity, disability, and mortality. Much of the strongest evidence to date implicating environmental factors in the development of autoimmunity has been based on well-established, large, longitudinal prospective cohort studies. Herein, we review the current state of knowledge on known environmental factors associated with the development of SARD and potential areas for future research. The risk attributable to any particular environmental factor ranges from 10-200%, but exposures are likely synergistic in altering the immune system in a complex interplay of epigenetics, hormonal factors, and the microbiome leading to systemic inflammation and eventual organ damage. To reduce or forestall the progression of autoimmunity, a better understanding of disease pathogenesis is still needed. Owing to the complexity and multifactorial nature of autoimmune disease, machine learning, a type of artificial intelligence, is increasingly utilized as an approach to analyzing large datasets. Future studies that identify patients who are at high risk of developing autoimmune diseases for prevention trials are needed.

Centre-based childcare in early childhood and child obesity: systematic review and meta-analysis protocol

ObjectivesCentre-based childcare has been identified as a promising environment for obesity prevention in early childhood, but the longitudinal relationships between attending centre-based childcare and child obesity are not well understood....

Is the rise in childhood obesity rates leading to an increase in hospitalizations due to dengue?

Background Obesity and diabetes are known risk factors for severe dengue. Therefore, we sought to investigate the association of obesity with increased risk of hospitalization, as there is limited information. Methods and findings Children aged 10 to 18 years (n = 4782), were recruited from 9 districts in Sri Lanka using a stratified multi-stage cluster sampling method. Details of previous admissions to hospital due to dengue and anthropometric measurements were recorded and seropositivity rates for dengue were assessed. The body mass index (BMI) centile in children aged 10 to 18, was derived by plotting the values on the WHO BMI-for-age growth charts, to acquire the percentile ranking. Results Although the dengue seropositivity rates were similar in children of the different BMI centiles, 12/66 (18.2%) seropositive children with a BMI centile &gt;97th, had been hospitalized for dengue, compared to 103/1086 (9.48%) of children with a BMI centile of &lt;97th. The logistic regression model suggested that BMI centiles 50th to 85th (OR = 1.06, 95% CI, 1.00 to 1.11, p = 0.048) and BMI centile of &gt;97th (OR 2.33, 95% CI, 1.47 to 3.67, p = 0.0003) was significantly associated with hospitalization when compared to children in other BMI categories. Conclusions Obesity appears to be associated with an increased risk of hospitalization in dengue, which should be further investigated in longitudinal prospective studies. With the increase in obesity in many countries, it would be important to create awareness regarding obesity and risk of severe disease and hospitalization in dengue.

The risk and protective factors for entering organized crime groups and their association with different entering mechanisms: A systematic review using ASReview

The aims of the current systematic review are to provide an overview of the available evidence concerning the risk and protective factors for entering organized crime groups (OCGs), to explore which entry mechanisms for entering OCGs are distinguished in the literature, and to assess whether different sets of risk and protective factors could be identified for each of these entry mechanisms. To achieve these aims, a systematic literature search for qualitative, quantitative, and mixed method studies was performed up to 19 April 2021. To be included in the current review, studies had to be of empirical nature and published in either English or Dutch. ASReview was used to facilitate the inclusion process, a reference check of the included studies was performed, and all included studies in prior reviews on this topic were checked for inclusion. This process resulted in 51 included studies. Relevant study and sample characteristics, information on risk and protective factors, and indicated entry mechanisms were derived from the included studies. In line with earlier reviews, we find relatively strong evidence that being male, belonging to an ethnic minority group, committing certain crimes prior to entry at a young(er) age, committing multiple offenses without being specialized, and having a criminally involved family and/or friends are risk factors for entering OCGs. Entering OCGs occurs via four different entry mechanisms: active recruitment, soliciting for membership, growing into and self-setup. Based on the included studies, the risk and protective factors for entering OCGs that are associated with these different entry mechanisms into OCGs seem to overlap. Although the current review provides grounds to suggest that, in addition to a general set of risk and protective factors for entering OCGs, there might be different risk and protective factors associated with different entry mechanisms, longitudinal prospective studies are needed to substantiate this suggestion.

Defining "High Recurrence" of Depressive Episodes for Predicting Diagnostic Conversion from Major Depressive Disorder to Bipolar Disorder: A 5-year Retrospective Study.

This study determined the threshold for recurrent depressive episodes that predicted conversion from major depressive disorder (MDD) to bipolar disorder (BD). We retrospectively reviewed the medical records of 296 patients diagnosed with MDD for a minimum of 5 years in two university hospitals. We examined their the Diagnostic and Statistical Manual of Mental Disorders, 5th edition diagnoses and detailed clinical information at the initial admission and yearly assessments after discharge to establish the threshold for recurrent depressive episodes indicating a risk of diagnostic conversion from MDD to BD. Optimal cut-offs were derived using receiver operating characteristic (ROC) curves. ROC curve analysis revealed that more than four recurrent depressive episodes was indicative of potential diagnostic conversion from MDD to BD (area under the curve, 0.604; sensitivity, 0.353; specificity, 0.855; positive predictive value, 0.421; negative predictive value, 0.816). These findings suggest that the best predictor of conversion from MDD to BD is more than four recurrent depressive episodes. Our findings have the potential to enhance diagnostic accuracy and treatment efficiency. To validate our results, longitudinal prospective studies are necessary.

E014 Migration of the large complex dataset of the UK Juvenile Dermatomyositis Cohort Biomarker Study: challenges and lessons

Abstract Background/Aims In rare disease research, longitudinal prospective cohort studies are important tools to generate invaluable real-world evidence to inform treatment choices and understand outcomes. The Juvenile Dermatomyositis Cohort Biomarker Study &amp; Repository (JDCBS) is a multi-centre, prospective longitudinal cohort study with linked biobank, established in 2000, with 17 active UK-Centres contributing data and samples. It supported over 60 projects generating new evidence, treatments and biomarkers in the field of juvenile myositis. The database in use until March 2023 used aged technology which did not sufficiently meet current needs of the study. REDCap is secure web application for hosting online databases, able to support online longitudinal data capture for multi-centre research studies. The aim of this project was to build and deliver a future-proofed environment and migrate the large JDCBS dataset into the REDCap platform. Methods Clinical, laboratory and outcome data at clinic visits were previously captured through a web interface which loaded data into an MS-Access back-end database. In this project, an internationally agreed set of data elements for use in research in juvenile myositis was adopted and a new data entry platform built, using REDCap and a Trusted Research Environment hosted at Great Ormond Street Digital Research Environment. A multidisciplinary team was formed to deliver migration, including clinicians, study investigators, systems analysts, and health informatics data scientists. Careful comparison of fields in the existing database to those in the internationally agreed dataset before delivery of the new REDCap database and migration of the legacy data took place. Results Key steps to deliver the REDCap interface and migrate the data included: 1. Agreement of data elements to be included, dropped or added, compared to the legacy dataset; 2. Design of study forms and fields within REDCap; 3. Testing new interface; 4. Script design and testing for migration; 5. Data cleaning of legacy dataset; 6. Training 15 collaborators and REDCap accounts management for 63 collaborators; 6. Migration of legacy dataset and quality control of migrated data; 7. Post-migration data checking and feedback on use of the new platform; 8. Summary reports of process, data quality and audit trail of project. In total, 670 patient records and 7431 clinical forms, with data from 338 data fields, were successfully migrated to the new REDCap database. A median value of 11 clinical forms (IQR: 6-18), and 3,718 data points (IQR: 2,028-6084) were migrated per patient. Conclusion Migration of a multi-dimensional longstanding study data set is a complex multi-step task requiring multi-disciplinary engagement of stakeholders. Key elements to achieve success include early agreement of data fields for inclusion, strict definitions of fields, regular engagement with database users, providing robust training, enabling feedback, and acceptance that research datasets should strive to be parsimonious in fields collected. Disclosure D. Cancemi: None. R. Hamilton: None. S. Varakliotis: None. H.D. Nguyen: None. N. Sabire: None. N. Martin: None. L. McCann: None. C. Papadopoulou: None. L. Wedderburn: Other; LW has non-renumerated collaboration with Novartis Inc, relevant to this work.

Dental Caries and Salivary Immunoglobulin A in Down Syndrome

Down syndrome (DS) is defined as trisomy chromosome 21, which is observed to be the most prevalent autosomal genetic anomaly. Salivary immunoglobulin A (sIgA) plays an important role in defence mechanism against the microbial pathogens that can invade the surface of mucosa. In children with DS, raised sIgA levels cause an increase in immune mechanism against dental caries. The evidence about the salivary IgA levels in children suffering from Down syndrome is contradictory and limited in the literature. Thus, there is a terrible requirement to conduct more longitudinal prospective studies on saliva of DS patients taking large sample sizes to assess the molecular interactions. The present review is aimed to evaluate the association of Dental caries and salivary immunoglobulin A in Down syndrome individuals. The sources were searched from a database of PubMed from 2004 to 2023 (last 19 years). The inclusion criteria included key words of microdontia, delayed eruption, dental anomalies, retained teeth, anodontia, fissured lip and tongue, macroglossia, hypodontia in Down syndrome. The 22 articles that met the selection criteria (most of them were review article and some observational studies) were included to this review, of which some of the studies have been conducted to assess the role of sIgA in relation to dental caries and observed that increased sIgA levels decrease the rate of incidence of dental caries. The present review revealed that patients suffering with Down syndrome are at an increased risk of dental caries because of impaired motor activities, malocclusion and affected quality of life.

Maternal diabetes and fracture risk in offspring: a population-based analysis.

Factors affecting intrauterine environment exerts influence on skeletal health and fracture risk in later life. Diabetes during pregnancy is known to influence birth weight and is associated with fetal overgrowth. However, the effects of maternal diabetes on fracture risk in offspring is unknown. This study was aimed to evaluate the association between maternal diabetes and fracture risk in offspring. Using population-based administrative health data for Manitoba, Canada, we identified deliveries complicated by gestational diabetes and type 2 diabetes between April 1, 1980, and March 31, 2020. The cohort was followed for a median of 15.8yr. The primary outcome was any incident fracture in offspring. Secondary outcomes were long bone upper extremity fracture, long bone lower extremity fracture, vertebral fracture, and any non-trauma fractures. Cox proportional hazard regression models were used to estimate fracture risk in offspring by maternal diabetes status adjusted for relevant covariates. Of the 585 176 deliveries, 26 397 offspring were born to women with diabetes (3.0% gestational diabetes and 1.5% type 2 diabetes), and 558 779 were born to women without diabetes. The adjusted risk for any fracture was 7% (hazard ratio, 1.07; 95% CI, 2.7-11.5%) higher in the offspring of mothers with diabetes than offspring of mothers without diabetes. Types of fractures were similar between the 2 groups with a predominance of long bone upper extremity fractures. In conclusion, maternal diabetes was associated with a modest increase in fracture risk in offspring. Longitudinal prospective studies are needed to understand intrauterine and postnatal factors that may influence fracture risk in the offspring of mothers with diabetes.

Clinical and genetic contributions to medical comorbidity in bipolar disorder: a study using electronic health records-linked biobank data.

Bipolar disorder is a chronic and complex polygenic disease with high rates of comorbidity. However, the independent contribution of either diagnosis or genetic risk of bipolar disorder to the medical comorbidity profile of individuals with the disease remains unresolved. Here, we conducted a multi-step phenome-wide association study (PheWAS) of bipolar disorder using phenomes derived from the electronic health records of participants enrolled in the Mayo Clinic Biobank and the Mayo Clinic Bipolar Disorder Biobank. First, we explored the conditions associated with a diagnosis of bipolar disorder by conducting a phenotype-based PheWAS followed by LASSO-penalized regression to account for correlations within the phenome. Then, we explored the conditions associated with bipolar disorder polygenic risk score (BD-PRS) using a PRS-based PheWAS with a sequential exclusion approach to account for the possibility that diagnosis, instead of genetic risk, may drive such associations. 53,386 participants (58.7% women) with a mean age at analysis of 67.8 years (SD = 15.6) were included. A bipolar disorder diagnosis (n = 1479) was associated with higher rates of psychiatric conditions, injuries and poisonings, endocrine/metabolic and neurological conditions, viral hepatitis C, and asthma. BD-PRS was associated with psychiatric comorbidities but, in contrast, had no positive associations with general medical conditions. While our findings warrant confirmation with longitudinal-prospective studies, the limited associations between bipolar disorder genetics and medical conditions suggest that shared environmental effects or environmental consequences of diagnosis may have a greater impact on the general medical comorbidity profile of individuals with bipolar disorder than its genetic risk.

Thyroiditis and COVID-19: focus on pediatric age. A narrative review.

In light of the growing concern over the possible link between SARS-CoV2 infection and autoimmune diseases, we conducted a review to investigate the impact of the pandemic outbreak on thyroid diseases. We carried out a narrative review of all pediatric cases described in the literature, mainly focusing on the possible association of COVID-19 with the incidence of autoimmune and post-infective thyroid diseases (namely Hashimoto's Thyroiditis (HT), Grave's Disease (GD) and Sub-Acute Thyroiditis (SAT)). We also felt it was necessary to provide a brief review of Non-thyroidal Illness Syndrome (NTIS) and Multisystem Inflammatory Syndrome in Children (MIS-C) because of their overlap with thyroiditis. There is currently no conclusive evidence linking SARS-CoV-2 infection with an increased incidence of autoimmune thyroiditis (AT) in pediatric age. However, SAT may be a mild complication of SARS-CoV-2 infection, as is the case with other viral infections. SAT typically resolves on its own and does not require treatment. NTIS may be associated with inflammatory complications, such as MIS-C, and admission to intensive care. It may also be considered a prognostic risk factor for severe disease. The hypothesized pathogenetic mechanisms of thyroid damage in COVID-19 include direct damage due to the significant expression of angiotensin-converting enzyme 2 (ACE2) in the thyroid gland, which is a ligand for the virus, and indirect damage due to immune dysregulation, such as the overproduction of IL-6, which is thought to be part of the pathogenesis of thyroiditis. However, due to the limited evidence available, further prospective longitudinal studies are required to clarify the relationship between COVID-19 and thyroid disease in children and adolescents, as well as to investigate any potential long-term consequences.

Exercise as Treatment for "Stress-Related" Mental Disorders.

The beneficial impact of physical activity on preventing and treating mental disorders has captured growing (research) interest. This article aims to provide a concise overview of essential evidence regarding the effectiveness and underlying mechanisms of physical activity for individuals with mental disorders clustered as "stress-related" conditions. Empirical findings (e.g., longitudinalprospective studies, interventional randomized-controlled-trials, reviews, meta-analyses) regarding the effects of physical activity in the prevention and treatment of stress-related mental disorders are summarized. Furthermore, potential mechanisms underlying these effects are discussed, and recommendations regarding the use of physical activity are outlined. The majority of studies indicate good efficacy of physical activity in prospectively lowering the risk for the incidence of subsequent stress-related mental disorders as well as in the treatment of manifest disorders. Most evidence targets unipolar depressive disorder and, secondly, anxiety disorders. Research regarding posttraumatic stress disorder, obsessive-compulsive disorders, and somatoform disorders is promising but scarce. Physical activity seems to be useful as a stand-alone-treatment as well as in combination with other psychotherapeutic or pharmacological treatments. Multiple intertwined physiological, psychological, and social mechanisms are assumed to mediate the beneficial effects. Recommendations regarding physical activity can orientate on official guidelines but should consider the individual needs and circumstances of each subject. In summary, physical activity seems to be effective in the prevention and treatment of stressrelated mental disorders and, therefore, should be fostered in healthcare-settings. Future studies are needed to clarify partly inconsistent patterns of results and to close research gaps, e.g., concerning somatoform disorders.

Delirium is more common and associated with worse outcomes in Parkinson's disease compared to older adult controls: results of two prospective longitudinal cohort studies.

Inpatient prevalence of Parkinson's disease (PD) delirium varies widely across the literature. Delirium in general older populations is associated with adverse outcomes, such as increased mortality, dementia, and institutionalisation. However, to date there are no comprehensive prospective studies in PD delirium. This study aimed to determine delirium prevalence in hospitalised PD participants and the association with adverse outcomes, compared to a control group of older adults without PD. Participants were hospitalised inpatients from the 'Defining Delirium and its Impact in Parkinson's Disease' and the 'Delirium and Cognitive Impact in Dementia' studies comprising 121 PD participants and 199 older adult controls. Delirium was diagnosed prospectively using the Diagnostic and Statistical Manual of Mental Disorders 5th Edition criteria. Outcomes were determined by medical note reviews and/or home visits 12months post hospital discharge. Delirium was identified in 66.9% of PD participants compared to 38.7% of controls (p < 0.001). In PD participants only, delirium was associated with a significantly higher risk of mortality (HR = 3.3 (95% confidence interval [CI] = 1.3-8.6), p = 0.014) and institutionalisation (OR = 10.7 (95% CI = 2.1-54.6), p = 0.004) 12months post-discharge, compared to older adult controls. However, delirium was associated with an increased risk of developing dementia 12months post-discharge in both PD participants (OR = 6.1 (95% CI = 1.3-29.5), p = 0.024) and in controls (OR = 13.4 (95% CI = 2.5-72.6), p = 0.003). Delirium is common in hospitalised PD patients, affecting two thirds of patients, and is associated with increased mortality, institutionalisation, and dementia. Further research is essential to understand how to accurately identify, prevent and manage delirium in people with PD who are in hospital.

Assessing severity of COVID-19 and the development of multi system inflammatory syndrome in children (MIS-C) in pediatric patients with atopic disease.

Background: Research surrounding the coronavirus disease 2019 (COVID-19) pandemic and its impact on patients who are atopic has mainly focused on adults. After the delta variant showed increased rates of COVID-19 in children, the pediatric population needs to be assessed as well. Objective: The objective was to assess and report outcomes in patients with COVID-19 and with and without certain atopic diseases in our patient cohort at the University of Mississippi Medical Center. Methods: We conducted a retrospective review of patients by using a de-identified data base that allows querying via medical claims codes from the University of Mississippi Medical Center's Research Data Warehouse. We searched for patients who were COVID-19 positive and ages 0-21 years from January 1, 2020, to December 31, 2021. We then divided this population into two cohorts: an atopic population and a non-atopic population. The incidence of hospitalizations, intensive care unit (ICU) admissions, death, length of stay, inhaled corticosteroid prescription history, and the incidence of multi-system inflammatory syndrome in children (MIS-C) outcomes in the two populations were collected. Results: There were 5261 patients ages 0-21 years and with confirmed COVID-19. After exclusion criteria were applied, there were 1420 patients in the atopic cohort and 2525 patients in the non-atopic cohort. There were more hospitalizations and a longer length of stay in the atopic population. Mortality was equivalent in the atopic and non-atopic populations. There were more ICU admissions in the atopic population. There were 101 patients total with the diagnosis of MIS-C, and the incidence of MIS-C was similar in the atopic and non-atopic populations. There were more patients who were atopic on inhaled corticosteroid than were the patients who were non-atopic. Conclusion: This study sought to further elucidate whether asthma, atopic dermatitis, and allergic rhinitis in pediatric patients was associated with severe COVID-19. Our study showed increased hospitalizations, length of stay, and intensive care in the atopic population but similar outcomes in mortality and the development of MIS-C. Future longitudinal prospective studies are needed to assess the long-term effects on patient's atopic disease after COVID-19 infection.