6 research outputs found
Case Reports1. A Late Presentation of Loeys-Dietz Syndrome: Beware of TGFβ Receptor Mutations in Benign Joint Hypermobility
Background: Thoracic aortic aneurysms (TAA) and dissections are not uncommon causes of sudden death in young adults. Loeys-Dietz syndrome (LDS) is a rare, recently described, autosomal dominant, connective tissue disease characterized by aggressive arterial aneurysms, resulting from mutations in the transforming growth factor beta (TGFβ) receptor genes TGFBR1 and TGFBR2. Mean age at death is 26.1 years, most often due to aortic dissection. We report an unusually late presentation of LDS, diagnosed following elective surgery in a female with a long history of joint hypermobility. Methods: A 51-year-old Caucasian lady complained of chest pain and headache following a dural leak from spinal anaesthesia for an elective ankle arthroscopy. CT scan and echocardiography demonstrated a dilated aortic root and significant aortic regurgitation. MRA demonstrated aortic tortuosity, an infrarenal aortic aneurysm and aneurysms in the left renal and right internal mammary arteries. She underwent aortic root repair and aortic valve replacement. She had a background of long-standing joint pains secondary to hypermobility, easy bruising, unusual fracture susceptibility and mild bronchiectasis. She had one healthy child age 32, after which she suffered a uterine prolapse. Examination revealed mild Marfanoid features. Uvula, skin and ophthalmological examination was normal. Results: Fibrillin-1 testing for Marfan syndrome (MFS) was negative. Detection of a c.1270G > C (p.Gly424Arg) TGFBR2 mutation confirmed the diagnosis of LDS. Losartan was started for vascular protection. Conclusions: LDS is a severe inherited vasculopathy that usually presents in childhood. It is characterized by aortic root dilatation and ascending aneurysms. There is a higher risk of aortic dissection compared with MFS. Clinical features overlap with MFS and Ehlers Danlos syndrome Type IV, but differentiating dysmorphogenic features include ocular hypertelorism, bifid uvula and cleft palate. Echocardiography and MRA or CT scanning from head to pelvis is recommended to establish the extent of vascular involvement. Management involves early surgical intervention, including early valve-sparing aortic root replacement, genetic counselling and close monitoring in pregnancy. Despite being caused by loss of function mutations in either TGFβ receptor, paradoxical activation of TGFβ signalling is seen, suggesting that TGFβ antagonism may confer disease modifying effects similar to those observed in MFS. TGFβ antagonism can be achieved with angiotensin antagonists, such as Losartan, which is able to delay aortic aneurysm development in preclinical models and in patients with MFS. Our case emphasizes the importance of timely recognition of vasculopathy syndromes in patients with hypermobility and the need for early surgical intervention. It also highlights their heterogeneity and the potential for late presentation. Disclosures: The authors have declared no conflicts of interes
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Estimating impacts of the Great Recession on adolescent depressive episodes and mental health service utilization with disparities by poverty in the United States
Introduction: There is growing evidence for increased prevalence of poor adolescent mental health, including depression, in the United States. Increases in adolescent depression beginning around 2008-2010 coincided with the timing of the Great Recession and there are plausible mechanisms through which economic recessions may influence adolescent depression (e.g., caregiver job loss, household economic hardship). More research is needed to understand the potential relationship between the 2007-2009 Great Recession and long-term impacts on mental health by household poverty, as many mechanisms (e.g., cumulative familial stress) can impact adolescent mental health after the peak of a recession passes. The objective of this dissertation is to examine the associations between economic recessions and adolescent depression. This dissertation includes five chapters: first, an introduction; second, a literature review to examine evidence of time trends and birth cohort effects in depressive disorders and symptoms among adolescents in recent years; third, an empirical study to assess changes in adolescent depression and depression treatment, including differences by household poverty occurring at the beginning of the Great Recession; fourth, an empirical study to estimate potential longer-term impacts of the Great Recession by examining whether young adults from birth cohorts who were adolescents at the time of the Great Recession had higher risk of MDE and mental health treatment use as young adults compared with birth cohorts who were adolescents and surveyed prior to the Great Recession with potential differences by household poverty; and fifth, a conclusion to summarize results and discuss implications for future research.
Methods: The integrative systematic literature review included 10 studies related to the United States, adolescent populations, birth year and time trends, and depressive symptoms or disorders. The two empirical aims utilized data from the National Survey on Drug Use and Health (NSDUH), a national survey assessing behavioral health among participants aged 12 and older. For the first empirical aim, I analyzed data for adolescents ages 12-17 participating in the 2004-2019 NSDUH (N = 256,572). For the second empirical aim, I included young adults ages 18-29 from the 2005-2019 NSDUH (N = 135,158). For this aim, the main exposure measure was belonging to birth cohorts (1990-1994) who were adolescents during the Great Recession and surveyed in 2008-2019 versus those from birth cohorts (1976-1989) that did not experience the Great Recession and were surveyed prior to the Great Recession in 2005-2007. For both empirical aims, I measured past year DSM-IV and DSM-5 major depressive episodes (MDE) from self-reported symptoms. MDE treatment was assessed among those with past year MDE, excluding those who were already successfully treated for MDE. For the first empirical aim, I tested how MDE and MDE treatment conditioned on MDE changed from pre-Great Recession (2004 to Fall 2007) to post-Great Recession (Winter 2007 to 2019) using interrupted time-series (ITS) segmented regression models accounting for seasonality (January-March, April-June, July-September, October-December) and autocorrelation. For the second empirical aim, regression models assessed the relationships between the birth cohort exposure measure and MDE and mental health treatment utilization adjusting for age, gender, race/ethnicity, educational attainment, and insurance status. Both empirical aims tested effect modification by household poverty.
Results: The review of 10 studies found increases in depressive symptoms and disorders in adolescents across recent survey years with increases observed between 1991 and 2020. Of the 3 articles that assessed birth cohort trends, birth cohort trends were less prominent than time period trends. Proposed explanations for increases included social media, economic-related reasons, changes in mental health screening and diagnosis, changes to mental health stigma and treatment and, in more recent years, the COVID-19 pandemic. In the first empirical study, I illustrated that the Great Recession was not associated with an immediate change in MDE prevalence (β: -0.77, 95% CI: -2.23, 0.69). However, following the Great Recession, the increase in MDE prevalence accelerated (β: 0.29, 95% CI: 0.13, 0.44). The Great Recession was not associated with acute changes in adolescent MDE treatment (β: -2.87, 95% CI: -7.79, 2.04) nor longer-term slope effects (β: 0.03, 95% CI: -0.46, 0.51). Evidence of interaction by household poverty was not observed for either the MDE or MDE treatment outcome. In the second empirical aim, interaction between the birth cohort exposure and household poverty was observed for MDE (F=10.17, df=2, p=<0.0001), but not for mental health treatment use. Great Recession exposure effects were stronger among those at higher levels of household income. For example, among young adults who were living in households at two times the poverty threshold, those from birth cohorts who were exposed during adolescence to the Great Recession had higher odds of MDE compared with young adults from birth cohorts who were unexposed during adolescence to the Great Recession (adjusted odds ratio= 1.16, 95% CI= 1.04, 1.29).
Conclusions: Multiple cross-sectional surveys and cohort studies documented rising prevalence of depressive symptoms and disorder among adolescents from 1991-2020. The Great Recession coincided with accelerated trends of increasing MDE, but not MDE treatment of these adolescents. Contrary to my hypothesis, the strength of changes in the rate of increase in MDE did not differ by household poverty and adolescents from households living in poverty, who likely experienced a greater financial burden during the recession, did not experience an increase in the rate of MDE. Birth cohort effects by household poverty were observed and exposure to the Great Recession during adolescence was associated with long-term effects on MDE, but not mental health treatment utilization, during young adulthood compared with those not exposed to the Great Recession. Young adults from higher income households who were exposed to the Great Recession had heightened likelihood of MDE. Future research should explore alternative drivers of MDE during the 2010s, as poverty-specific cohort analyses did not show that those living in poverty who likely experienced the greatest burden of a recession financially had increased risk of MDE