Faculty Bibliography

Introduction: Sleep may play a role in AD pathogenesis, but the timing, role, and extent to which sleep disturbances in late-life are associated with increasing burden of AD neuropathology remains unclear. Sleep spindles have been implicated in sleep quality. Wakefulness is mediated by an arousal system beginning in the brainstem and continuing on to the diencephalon and innervating the thalamus, the region where sleep spindle oscillations are generated. In AD pathology, hyperphosphorylated tau (P-Tau) protein accumulates in the brainstem, from where it spreads to the entorhinal cortices, hippocampi and other brain regions. These tau aggregates may interfere with the sleep-wake cycle resulting in down-regulation of sleep spindles and associated sleep disruption. Increased CSF P-tau and T-tau levels are likely related to the formation of neurofibrillary tangles in the brainstem and limbic system (Braak stages I-IV). Methods: 49 cognitively normal (CDR=0) elderly (66.95 +/- 7.76 years) subjects completed a structural MRI, lumbar puncture (LP) and nocturnal polysomnography (NPSG) within 4.65 +/- 6.81 months of the LP. From the NPSG, spindle frequency and density were analyzed for stages NREM1, NREM2 and NREM3, using an automated optimization algorithm which decomposes the EEG as a sum of transient and oscillatory components. This was used to detect the spindles and a Fourier analysis was performed to evaluate the spindle frequency in Hz. Results: Spindle frequency and density in NREM2 sleep were inversely associated with CSF P-tau (r= -0.355, p<0.05; r=-0.476, p<0.05) and CSF T-tau (r=-0.405, p<.05; r=-0.542, p<.05) using partial correlation controlling for age and ApoE4 allele. There were no associations between spindle frequency or density and CSF P-tau or CSF T-tau in stages NREM1, NREM3. Conclusion: The association of spindle frequency and density in NREM2 to CSF P-tau and CSF T-tau in cognitively normal elderly suggest either that tau pathology may produce an early downstream effect on sleep spindles, or that changes in sleep spindles can identify a process relating to tau pathology. Whether the association of tau to spindles is a non-specific effect of tau on increasing sleep fragmentation in general remains an area of active investigation

BACKGROUND:Primary cesarean deliveries are a major contributor to the large increase in cesarean delivery rates in the United States over the past 2 decades and are an essential focus for the reduction of related morbidity and costs. Studies have shown that primary cesarean delivery rates among low-risk women in the United States vary 3-fold across hospitals and are not explained by differences in patient case-mix. However, the extent to which maternal vs hospital characteristics contribute to this variation remains poorly understood because previous studies were limited in scope and did not assess the influence of factors such as maternal ethnicity subgroups or prepregnancy obesity. OBJECTIVE:We assessed the contribution of individual- and hospital-level risk factors to the hospital variation in primary cesarean delivery rates among low-risk women in Florida. STUDY DESIGN/METHODS:Our population-based retrospective cohort study used Florida's linked birth certificate and hospital discharge records for the period of 2004-2011. The study population was comprised of 412,192 nulliparous, singleton, vertex, live births with labor at 37-40 weeks gestation in 122 nonmilitary delivery hospitals. Data were analyzed with logistic mixed-effects regression with cesarean delivery as the outcome. This approach provided adjusted risk estimates at an individual and hospital level and the estimated percent of hospital variation statewide that was explained by these factors. RESULTS:The primary cesarean delivery rate in the study population was 23.9%, with hospital-specific estimates that ranged from 12.8-47.3%. Leading risk factors for cesarean delivery were maternal age ≥35 years (adjusted relative risk, 2.22), prepregnancy obesity (body mass index, ≥30 kg/m(2); adjusted relative risk, 1.73), medical risk conditions (adjusted relative risk, 1.72), labor induction (adjusted relative risk, 1.52), and delivery in hospitals located in Miami-Dade County (adjusted relative risk, 1.73). Hospital geographic location was a significant effect modifier for prepregnancy obesity, medical conditions, and labor induction (P < .05), with a tendency towards lower adjusted relative risks for these factors in Miami-Dade County relative to other Florida regions. Conversely, Miami-Dade County had an increased prevalence of higher-risk ethnic subgroups, such as Cuban or Puerto Rican mothers, and also substantially higher adjusted relative risks that were associated with practice-related factors, such as delivery during weekday hours. Whereas hospital geographic location contributed to 39.6% of the observed variation statewide, the estimated contribution of maternal ethnicity ranged from 1.6-15.7% among Florida regions. CONCLUSIONS:Hospital geographic location contributes to hospital variation in primary cesarean delivery rates among low-risk women in Florida. In contrast to previous studies, our findings suggest that individual level risk factors such as maternal ethnicity also contribute to some of this variation, with differing extent by region. These individual factors likely interact with practice factors and add to the variation. This study was limited by not including maternal Bishop score before induction or obstetrics provider in the analysis. These were not available on the dataset but likely contribute to the variation. Our findings suggest potential issues to consider in quality improvement efforts, such as the need for future qualitative research that focuses on mothers in higher-risk ethnic subgroups and providers in high-rate hospitals, particularly those in Miami-Dade County. These studies may help to identify potential cultural differences in maternal beliefs and expectations for delivery and maternal reasons for differences in obstetrics practices.