Is repeated childhood fracture related to areal bone density or body composition in middle age?

Childhood fracture is common, but whether it predicts adult fracture is not clear. Repeat childhood fracture was associated with adult (≤ 45 years) fracture, and in women, lower areal bone density was associated with repeat childhood fracture. Identifying fracture-prone children can modify adult fracture risk management. INTRODUCTION: A quarter of boys and 15% of girls will suffer multiple fractures, but it is not clear whether multiple fractures during growth predict fracture risk and areal bone density in adulthood. This study evaluated whether children who repeatedly fracture were at increased risk of low areal bone density, abnormal body composition, and fractures by age 45. METHODS: A subsample of a large birth cohort study with childhood fracture cases had areal bone density assessed at age 45 years. Participants were questioned regularly across their lifetime about fractures during childhood (ages 0-18 years of age) and adulthood (any fracture between 18 and 45 years). The number of fractures was collapsed into three categories: no fractures; 1 fracture; and > 1 fracture, separately for child and adult groups. RESULTS: At age 45 years, areal bone mineral density (g/cm2) and body composition were measured with dual X-ray absorptiometry in n = 555 participants. Compared to no fractures, twice as many girls (14% vs 7%, P = 0.156) and boys (31.4% vs 14.1%, P = 0.004) who repeatedly fractured in childhood sustained multiple fractures as adults. Both girls and boys who were fracture-free tended to remain fracture-free as adults (79.8% compared with 62.8%, P = 0.045, and 64.8% compared with 51.4%, P = 0.025, in males and females, respectively). Participants were more than twice as likely to fracture repeatedly as adults if they had sustained multiple fractures as a child (OR 2.5 95% CI: 1.4, 4.6). Women who repeatedly fractured during childhood had lower areal bone density, whereas repeated fracturing during childhood was not associated with areal bone density or body composition in men, even after adjustment for other factors known to influence fracture history. CONCLUSION: Childhood fracture history is associated with persistent skeletal fragility in adulthood (≤ 45 years), even after adjustment for behavioral and demographic factors known to influence fracture history.

Pharmacologic Treatment of Noninfectious Uveitis.

Uveitis encompasses a spectrum of diseases whose common feature is intraocular inflammation, which may be infectious or noninfectious in etiology (Nussenblatt and Whitcup 2010). Infectious causes of uveitis are typically treated with appropriate antimicrobial therapy and will not be discussed in this chapter. Noninfectious uveitides are thought have an autoimmune component to their etiology and are thus treated with anti-inflammatory agents.

Implementation of universal screening for substance use in pregnancy in a public healthcare system.

Objective: Screening questionnaires are one option for identification of at-risk substance use and substance use disorder (SUD) during pregnancy. We report the experience of a single institution following universal implementation of a brief screening tool for self-reported substance use at the first prenatal encounter. Study Design: This is a prospective implementation study evaluating screening for substance use in pregnancy in a large safety net healthcare system. Universal screening with the National Institute of Drug Abuse (NIDA) Quick Screen V1.0 was integrated into the electronic medical record (EMR) and administered at the first point of contact with the healthcare system. SUD was identified initially with diagnosis within the EMR by a healthcare provider and was confirmed with toxicology (maternal or neonatal) results corroborating a pattern of substance use and maternal and neonatal ICD-10 codes for SUD. Patients identified with SUD were then classified as moderate or severe SUD based on criteria established by the Diagnostic and Statistical Manual of Mental Disorders, 5th edition. We measured rates of NIDA implementation across different healthcare settings, evaluated NIDA concordance with ascertainment of SUD, and compared adverse pregnancy outcomes associated with moderate and severe SUD. Results: From July 28, 2021, through June 25, 2022, 14,634 unique pregnant individuals accessed care at ambulatory and acute care sites. Universal implementation of the NIDA Quick Screen identified at-risk substance use in 2146 (14.7%) of those who accessed our system, or 17.1% of 12,550 screened across the system, with greater screen completion in ambulatory over acute care settings. SUD was identified in 256 (1.7%) of 14,634 individuals and moderate or severe SUD was identified in 184 (1.3%). Among those with moderate or severe SUD, 90 (48.9%) were NIDA positive, 22 (12.0%) NIDA negative, and 72 (39.1%) unscreened. Of 94 individuals with NIDA discordance or who were unscreened 76 (81%) accessed initial care through an acute care setting. Of 96 individuals with opioid use disorder, 68 (70.8%) were treated with medication-assisted therapy, and 56 (58.3%) were screened with the NIDA Quick Screen. Among delivered individuals with available outcomes, those with moderate or severe SUD were less likely to seek prenatal care (71 (76%) vs 9852 (98%), <0.001)) and more likely to deliver before 37 weeks, (18 (20%) vs 909 (9%), RR (95% CI) 2.13 (1.40, 3.24)) compared to individuals without SUD. Neonates exposed to moderate or severe SUD were more likely to have birth weight <10th centile for gestational age (20 (22%) vs 1147 (12%), RR (95% CI) 1.92 (1.29, 2.85)) and require admission to the neonatal intensive care unit (NICU) (19 (21%) vs 964 (10%), RR (95%) 1.95 (1.30, 2.93)). Conclusion: Universal screening was implemented across a large public healthcare system at a high rate, with higher rates of implementation in ambulatory settings. NIDA successfully identified at-risk substance use in 17% of the SUD cohort but failed to identify more than 50% of patients with moderate or severe SUD. Patients with moderate and severe SUD accessed care primarily through the emergency department and experienced higher rates of adverse obstetric and neonatal outcomes. Future efforts to identify, engage, and retain this highest-risk group are needed.

The human placenta project: Funded studies, imaging technologies, and future directions.

The placenta plays a critical role in fetal development. It serves as a multi-functional organ that protects and nurtures the fetus during pregnancy. However, despite its importance, the intricacies of placental structure and function in normal and diseased states have remained largely unexplored. Thus, in 2014, the National Institute of Child Health and Human Development launched the Human Placenta Project (HPP). As of May 2023, the HPP has awarded over $101 million in research funds, resulting in 41 funded studies and 459 publications. We conducted a comprehensive review of these studies and publications to identify areas of funded research, advances in those areas, limitations of current research, and continued areas of need. This paper will specifically review the funded studies by the HPP, followed by an in-depth discussion on advances and gaps within placental-focused imaging. We highlight the progress within magnetic reasonance imaging and ultrasound, including development of tools for the assessment of placental function and structure.

Multimodal Imaging in Masquerade Syndromes.

Masquerade syndromes present to uveitis clinics due to the appearance of inflammatory signs and chronic symptoms that are not responsive to conventional treatment. They are frequently misdiagnosed and treated as refractory inflammatory conditions, which delays appropriate diagnosis and management. This review of literature focuses on the commonly encountered masquerade syndromes and discusses the role of multimodal imaging in addressing these complex clinical presentations. We review the conventional imaging techniques for these patients and discuss emerging technological advances that may help in establishing a diagnosis. We present cases highlighting the utility of multimodal imaging in identifying the etiology.

Comparative efficacy of steroid-sparing therapies for non-infectious uveitis.

INTRODUCTION: Non-infectious uveitis encompasses a group of inflammatory eye diseases that can cause irreversible vision loss if left untreated or undertreated. In cases requiring stemic treatment, a step-wise treatment approach is often employed starting with corticosteroids for severe active disease, followed by initiation of steroid-sparing therapies to maintain inflammatory control and avoid the abundant complications of long-term corticosteroid use. AREAS COVERED: We review the current high-quality evidence comparing the efficacy of various systemic steroid-sparing agents in the treatment of non-infectious uveitis. For studies to be included, they had to have a prospective, randomized, comparative design or a retrospective design including at least 100 patients. EXPERT COMMENTARY: Given the rarity of uveitis and the heterogeneity of uveitic diseases, there are few randomized controlled studies that directly compare the relative efficacy of the various steroid-sparing immunosuppressive agents. Therefore, current treatment strategies are based mainly on data from observational series.

Impaired corticopontocerebellar tracts underlie pseudobulbar affect in motor neuron disorders.

OBJECTIVE: The objectives of the study were (1) to determine the prevalence and characteristics of pseudobulbar affect (PBA) in patients with primary lateral sclerosis (PLS) and amyotrophic lateral sclerosis (ALS) in an outpatient clinic population, and (2) to test the hypothesis that damage of inputs to the cerebellum, leading to cerebellar dysmodulation, is associated with PBA. METHODS: Chart review of all patients with PLS and ALS seen between 2000 and 2013. The examining neurologist documented the presence or absence of PBA in 87 patients. Forty-seven patients also had diffusion tensor imaging (DTI) studies. Tract-based spatial statistics were used to compare DTI of patients with and without PBA to identify altered white matter tracts associated with PBA. RESULTS: Thirty-one of 50 patients with PLS and 12 of 37 patients with ALS had PBA. Psychiatric/emotional assessment found congruence between mood and affect during episodes, but excessive magnitude of the response. DTI studies of 25 PLS and 22 ALS patient brains showed reduced fractional anisotropy of the corticospinal and callosal white matter tracts in all patients. Patients with PBA additionally had increased mean diffusivity of white matter tracts underlying the frontotemporal cortex, the transverse pontine fibers, and the middle cerebellar peduncle. CONCLUSIONS: PBA is common in PLS. Imaging findings showing disruption of corticopontocerebellar pathways support the hypothesis that PBA can be viewed as a "dysmetria" of emotional expression resulting from cerebellar dysmodulation.