Sacral neuromodulation device biofilm differs in the absence and presence of infection, harbors antibiotic resistance genes, and is reproducible in vitro.

INTRODUCTION/PURPOSE: Sacral neuromodulation (SNM) is effective therapy for overactive bladder refractory to oral therapies, and non-obstructive urinary retention. A subset of SNM devices is associated with infection requiring surgical removal. We sought to compare microbial compositions of explanted devices in the presence and absence of infection, by testing phase, and other clinical factors, and to investigate antibiotic resistance genes present in the biofilms. We analyzed resistance genes to antibiotics used in commercially-available anti-infective device coating/pouch formulations. We further sought to assess biofilm reconstitution by material type and microbial strain in vitro using a continuous-flow stir tank bioreactor, which mimics human tissue with an indwelling device. We hypothesized that SNM device biofilms would differ in composition by infection status, and genes encoding resistance to rifampin and minocycline would be frequently detected. MATERIALS/METHODS: Patients scheduled to undergo removal or revision of SNM devices were consented per IRB-approved protocol (IRB 20-415). Devices were swabbed intraoperatively upon exposure, with controls and precautions to reduce contamination of the surrounding field. Samples and controls were analyzed with next-generation sequencing and RT-PCR, metabolomics, and culture-based approaches. Associations between microbial diversity or microbial abundance, and clinical variables were then analyzed using t-tests and ANOVA. Reconstituted biofilm deposition in vitro using the bioreactor was compared by microbial strain and material type using plate-based assays and scanning electron microscopy. RESULTS: Thirty seven devices were analyzed, all of which harbored detectable microbiota. Proteobacteria, Firmicutes and Actinobacteriota were the most common phyla present overall. Beta-diversity differed in the presence versus absence of infection (p = 0.014). Total abundance, based on normalized microbial counts, differed by testing phase (p < 0.001), indication for placement (p = 0.02), diabetes mellitus (p < 0.001), cardiac disease (p = 0.008) and history of UTI (p = 0.008). Significant microbe-metabolite interaction networks were identified overall and in the absence of infection. 24% of biofilms harbored the tetA tetracycline/minocycline resistance gene and 53% harbored the rpoB rifampin resistance gene. Biofilm was reconstituted across tested strains and material types. Ceramic and titanium did not differ in biofilm deposition for any tested strain. CONCLUSIONS: All analyzed SNM devices harbored microbiota. Device biofilm composition differed in the presence and absence of infection and by testing phase. Antibiotic resistance genes including to rifampin and tetracycline/minocycline, which are used in commercially-available anti-infective pouches, were frequently detected. Isolated organisms from SNM devices demonstrated the ability to reconstitute biofilm formation in vitro. Biofilm deposition was similar between ceramic and titanium, materials used in commercially-available SNM device casings. The findings and techniques used in this study together provide the basis for the investigation of the next generation of device materials and coatings, which may employ novel alternatives to traditional antibiotics. Such alternatives might include bacterial competition, quorum-sensing modulation, or antiseptic application, which could reduce infection risk without significantly selecting for antibiotic resistance.

Early childhood trauma exposure and neurocognitive and emotional processes: Associations in young children in a partial hospital program.

Early childhood trauma has been linked to neurocognitive and emotional processing deficits in older children, yet much less is known about these associations in young children. Early childhood is an important developmental period in which to examine relations between trauma and executive functioning/emotion reactivity, given that these capacities are rapidly developing and are potential transdiagnostic factors implicated in the development of psychopathology. This cross-sectional study examined associations between cumulative trauma, interpersonal trauma, and components of executive functioning, episodic memory, and emotion reactivity, conceptualized using the RDoC framework and assessed with observational and performance-based measures, in a sample of 90 children (ages 4-7) admitted to a partial hospital program. Children who had experienced two or more categories of trauma had lower scores in episodic memory, global cognition, and inhibitory control as measured in a relational (but not computerized) task, when compared to children with less or no trauma. Interpersonal trauma was similarly associated with global cognition and relational inhibitory control. Family contextual factors did not moderate associations. Findings support examining inhibitory control in both relationally significant and decontextualized paradigms in early childhood, and underscore the importance of investigating multiple neurocognitive and emotional processes simultaneously to identify potential targets for early intervention.

The effect of a night shift nap on post-night shift performance, sleepiness, mood, and first recovery sleep: A randomized crossover trial.

OBJECTIVES: This study aimed to test the effect of a 30-minute nap versus a 2-hour nap opportunity taken during a simulated night shift on performance, fatigue, sleepiness, mood, and sleep at the end of shift and during post-night shift recovery. METHODS: We conducted a randomized crossover trial of three nap conditions (30-minute, 2-hour, and no-nap) during 12-hour simulated night shifts. We tested for differences in performance, fatigue, sleepiness, mood, and sleep during in-lab and at-home recovery. Performance was measured with the Brief Psychomotor Vigilance Test (PVT-B). Subjective ratings were assessed with single-item surveys. RESULTS: Twenty-eight individuals consented to participate [mean age 24.4 (standard deviation 7.2) years; 53.6% female; 85.7% Emergency Medical Services clinicians]. PVT-B false starts at the end of the 12-hour night shift (at 07:00 hours) and at the start of in-lab recovery (08:00 hours) were lower following the 2-hour nap versus other conditions (P<0.05). PVT-B response time at +0 minutes post-recovery nap was poorer compared to pre-recovery nap for the no-nap condition (P=0.003), yet not detected for other nap conditions (P>0.05). Sleepiness, fatigue, and some mood states were lower at most hourly assessments during the in-lab recovery period following the 2-hour nap condition compared to the other conditions. Sleep during recovery did not differ by duration of night shift nap. CONCLUSIONS: A 2-hour nap opportunity versus a 30-minute or no-nap opportunity is beneficial for performance, alertness, and mood post-night shift. No differences were detected in sleep during recovery.

Effect of Short versus Long Duration Naps on Blood Pressure during Simulated Night Shift Work: A Randomized Crossover Trial.

OBJECTIVE: Blunting of the sleep-related dip in blood pressure (BP) has been linked to numerous cardiovascular outcomes including myocardial infarction. Blunting of BP dipping occurs during night shift work and previous research suggest that a 60-min or longer on-shift nap is needed to restore normal/healthy BP dipping. We sought to determine the effect of different durations of napping on BP during and following simulated night shifts. We hypothesized that the greatest benefit in terms of restoration of normal BP dipping during night shift work would be observed during a longer duration nap versus a shorter nap opportunity. METHODS: We used a randomized crossover laboratory-based study design. Participants consented to complete three separate 72-hr conditions that included a 12-hr simulated night shift. Nap conditions included a 30-min and 2-hr nap compared to a no-nap condition. Ambulatory BP monitoring was assessed hourly and every 10-30 mins during in-lab naps. Blunted BP dipping during in-lab naps was the primary outcome. Goal enrollment of 25 (35 with attrition) provided 80% power to detect a mean difference of 5 mmHg in BP between nap conditions. RESULTS: Of the 58 screened, 28 were consented, and 26 completed all three 72-hr conditions. More than half (53.6%) were female. Mean age was 24.4 years (SD7.2). Most (85.7%) were certified as emergency medical technicians or paramedics. The mean percentage dip in systolic BP (SBP) and diastolic BP (DBP) did not differ between the 30-min and 2-hr nap conditions (p > 0.05), yet a greater proportion of participants experienced a 10-20% dip in SBP or DBP during the 2-hr nap versus the 30-min nap (p < 0.05). For every additional minute of total sleep during the 30-min nap, the percentage of SBP dip improved by 0.60%, and the percentage of DBP dip improved by 0.68% (p < 0.05). These improvements approximate to a 6% per minute relative advancement toward normal/healthy BP dipping. CONCLUSIONS: Restoration of a normal/healthy dip in BP is achievable during short and long duration nap opportunities during simulated night shift work. Our findings support the hypothesis that BP dipping is more common during longer 2-hr versus shorter 30-min naps. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04469803. Registered on 9 July 2020.

Are Short Duration Naps Better than Long Duration Naps for Mitigating Sleep Inertia? Brief Report of a Randomized Crossover Trial of Simulated Night Shift Work.

OBJECTIVE: We sought to test the effects of different duration naps on post-nap cognitive performance during simulated night shifts. METHODS: We used a randomized laboratory-based crossover trial design with simulated 12-hr night shifts and each participant completing three conditions of 72 hrs each (Clinicaltrials.gov; registration # NCT04469803). The three conditions tested included no-nap, a 30-min nap opportunity, and a 2-hr nap opportunity. Naps occurred at 02:00 hrs. Cognitive performance was assessed with the Brief 3-min Psychomotor Vigilance Test (PVT-B). Four PVT-B measures include: reaction time (RT in milliseconds (ms)), lapses (RT > 355 ms), false starts (reactions before stimulus or RT <100 ms), and speed (1,000/RT). The PVT-B was performed at the start of the simulated night shift (19:00), end of shift (07:00), pre-nap (02:00), and at 0 mins, 10 mins, 20 mins, and 30 mins following the 30-min and 2-hr nap conditions. Simultaneously, participants reported subjective ratings of fatigue and other constructs. RESULTS: Twenty-eight (15 female), mostly certified emergency medical technicians or paramedics, consented to participate. For all three conditions, looking within condition, PVT-B lapse performance at the end of the 12-hr simulated night shift (at 07:00) was poorer compared to shift start (p < 0.05). Performance on PVT-B speed, RT, and false starts were poorer at shift end than shift start for the no-nap and 30-min nap conditions (p < 0.05), but not for the 2-hr nap condition (p > 0.05). Compared to pre-nap measures, performance on the PVT-B assessed at 0 mins post-nap showed significant performance declines for lapses and speed for both the 30-min and 2-hr nap conditions (p < 0.05), but not at 10, 20, or 30 mins post-nap. After waking from the 2-hr on-shift nap opportunity (at 0 mins), participants rated sleepiness, difficulty with concentration, and alertness poorer than pre-nap (p < 0.05). Participants in the 30-min nap condition rated alertness poorer immediately after the nap (at 0 mins) compared to pre-nap (p < 0.05). CONCLUSIONS: While sleep inertia was detectable immediately following short 30-min and long 2-hr nap opportunities during simulated night shift work, deficits in cognitive performance and subjective ratings quickly dissipated and were not detectable at 10-30 mins post-nap.

The Emergency Medical Services Sleep Health Study: A cluster-randomized trial.

BACKGROUND: Greater than half of emergency medical services (EMS) clinician shift workers report poor sleep, fatigue, and inadequate recovery between shifts. We hypothesized that EMS clinicians randomized to receive tailored sleep health education would have improved sleep quality and less fatigue compared to wait-list controls after 3 months. METHODS: We used a cluster-randomized, 2-arm, wait-list control study design (clinicaltrials.gov identifier: NCT04218279). Recruitment of EMS agencies (clusters) was nationwide. Our study was powered at 88% to detect a 0.4 standard deviation difference in sleep quality with 20 agencies per arm and a minimum of 10 individuals per agency. The primary outcome was measured using the Pittsburgh Sleep Quality Index (PSQI) at 3-month follow-up. Our intervention was accessible in an online, asynchronous format and comprised of 10 brief education modules that address fatigue mitigation topics prescribed by the American College of Occupational Environmental Medicine. RESULTS: In total, 36 EMS agencies and 678 individuals enrolled. Attrition at 3 months did not differ by study group (Intervention = 17.4% vs. Wait-list control = 18.2%; p = .37). Intention-to-treat analyses detected no differences in PSQI and fatigue scores at 3 months. Per protocol analyses showed the greater the number of education modules viewed, the greater the improvement in sleep quality and the greater the reduction in fatigue (p < .05). CONCLUSIONS: While intention-to-treat analyses revealed no differences in sleep quality or fatigue at 3 months, per protocol findings identified select groups of EMS clinician shift workers who may benefit from sleep health education. Our findings may inform fatigue risk management programs.

Napping on the night shift and its impact on blood pressure and heart rate variability among emergency medical services workers: study protocol for a randomized crossover trial.

BACKGROUND: There is an emerging body of evidence that links exposure to shift work to cardiovascular disease (CVD). The risk of coronary events, such as myocardial infarction, is greater among night shift workers compared to day workers. There is reason to believe that repeated exposure to shift work, especially night shift work, creates alterations in normal circadian patterns of blood pressure (BP) and heart rate variability (HRV) and that these alterations contribute to increased risk of CVD. Recent data suggest that allowing shift workers to nap during night shifts may help to normalize BP and HRV patterns and, over time, reduce the risk of CVD. The risk of CVD related to shift work is elevated for emergency medical services (EMS) shift workers due in part to long-duration shifts, frequent use of night shifts, and a high prevalence of multiple jobs. METHODS: We will use a randomized crossover trial study design with three study conditions. The targeted population is comprised of EMS clinician shift workers, and our goal enrollment is 35 total participants with an estimated 10 of the 35 enrolled not completing the study protocol or classified as lost to attrition. All three conditions will involve continuous monitoring over 72 h and will begin with a 36-h at-home period, followed by 24 total hours in the lab (including a 12-h simulated night shift), ending with 12 h at home. The key difference between the three conditions is the intra-shift nap. Condition 1 will involve a simulated 12-h night shift with total sleep deprivation. Condition 2 will involve a simulated 12-h night shift and a 30-min nap opportunity. Condition 3 will involve a simulated 12-h night shift with a 2-h nap opportunity. Our primary outcomes of interest include blunted BP dipping and reduced HRV as measured by the standard deviation of the inter-beat intervals of normal sinus beats. Non-dipping status will be defined as sleep hours BP dip of less than 10%. DISCUSSION: Our study will address two indicators of cardiovascular health and determine if shorter or longer duration naps during night shifts have a clinically meaningful impact. TRIAL REGISTRATION: ClinicalTrials.gov NCT04469803 . Registered on 9 July 2020.

Ambulatory blood pressure monitoring among emergency medical services night shift workers.

OBJECTIVES: Higher 24-hour blood pressure (BP) and blunted BP dipping during sleep and night-time hours are associated with adverse health outcomes. Night shift work may affect 24-hour BP and dipping patterns, but empirical data in emergency medical services (EMS) clinician shift workers are sparse. We implemented ambulatory blood pressure monitoring (ABPM) in EMS workers to characterise BP during night shift work versus a non-workday, and sleep versus wake. METHODS: Participants worked night shifts. Hourly ABPM and wrist actigraphy (to measure sleep) were collected during two 24-hour periods, one scheduled night shift and one non-workday. Blunted BP dipping was defined as a BP decrease of <10%. RESULTS: Of 56 participants, 53 (53.6% female, mean age 26.5 (SD 7.5) years) completed the study. During daytime sleep on a workday, 49.1% of participants had blunted systolic BP (SBP) or diastolic BP (DBP) dipping. During night-time sleep on a non-workday, 25% had blunted SBP dipping and 3.9% blunted DBP dipping. Blunted SBP or DBP dipping occurred among all participants who did not nap during the night shift or who napped <60 min. Blunted SBP dipping occurred in only 14.3% of participants who napped 60-120 min. CONCLUSIONS: During night shift work, the BP dipping of EMS shift workers is blunted; however, most who nap for 60 min or longer experience a healthy dip in BP. The potential health consequences of these observations in EMS clinicians warrant further study.

Incidence and Morbidity of Radiation-Induced Hemorrhagic Cystitis in Prostate Cancer.

OBJECTIVE: To determine if reported incidence rates of hemorrhagic cystitis after radiation therapy for prostate cancer are accurate, to investigate the effect of different radiation modalities on the development of hemorrhagic cystitis and to assess its morbidity and treatment. MATERIALS AND METHODS: A retrospective chart review was completed of 709 patients at 2 Detroit Medical Center hospitals who underwent radiation therapy for prostate cancer between January 2000 and September 2015. In patients who developed hemorrhagic cystitis, we analyzed the incidence, radiation modality, morbidity, treatment, and complications. RESULTS: The incidence rate of hemorrhagic cystitis after radiation for prostate cancer was 11.1%. There was no significant difference between external beam and intensity-modulated radiation therapy and the development of hemorrhagic cystitis (P = .18). Patients developed hemorrhagic cystitis an average of 79.1 months (4-230 months) after radiation. The average number of admissions was 2.5 (1-9) with an average length of stay of 7.6 days (1-42 days). Fifty-two percent of patients required blood transfusion with an average of 4.3 units transfused per patient (1-33U). The most common treatment was cystoscopy with fulguration/clot evacuation in 86% of patients. Complications included urinary tract infection, acute kidney injury, urosepsis, and even death. CONCLUSION: The incidence of hemorrhagic cystitis following radiation therapy for prostate cancer is under-reported in the literature. Hemorrhagic cystitis is associated with high morbidity and complications for patients, requiring multiple hospitalizations, blood transfusions, and procedures. Advances in radiation have not significantly reduced the risk of developing hemorrhagic cystitis.

Predictors of Partial Hospital Readmission for Young Children with Oppositional Defiant Disorder.

This study aimed to: (1) examine rates of readmission among young children with oppositional defiant disorder (ODD) following discharge from a psychiatric partial hospital treatment program, and (2) examine child factors (i.e., age, sex, co-occurring diagnoses, suicidality) and family factors (i.e., parental depression, stress) as prospective predictors of readmission. Participants were 261 children (ages 3-7 years) who entered the study at the time of their initial program admission and who met DSM-IV criteria for ODD. Of these 261 children, 61 (23%) were subsequently readmitted, with most readmissions occurring within 1 year. Cox regression survival analyses demonstrated that younger child age, child suicidal thoughts and behavior, and child PTSD diagnosis were associated with decreased time to readmission. Findings suggest that young children with ODD who present with co-occurring suicidality or PTSD are at risk for readmission following partial hospitalization, with implications for treatment and aftercare planning.

Temper Loss and Persistent Irritability in Preschoolers: Implications for Diagnosing Disruptive Mood Dysregulation Disorder in Early Childhood.

Disruptive Mood Dysregulation Disorder (DMDD) is a new and controversial child psychiatric disorder characterized by persistent irritability and frequent temper loss. Among the controversies surrounding DMDD is whether the age of onset criterion-that DMDD may not be diagnosed before age 6 years-is justified. This study examined DMDD symptoms and associated patterns of psychiatric comorbidity, behavioral, and family functioning in a sample of 139 preschoolers (ages 4-0 to 5-11 years) admitted to an early childhood psychiatric day treatment program. DMDD symptoms were common in this acute clinical sample, with 63 children (45.3 %) presenting with frequent temper outbursts and chronic irritability. As compared to children who did not present with DMDD symptoms, these children demonstrated more aggression and emotional reactivity and lower receptive language skills, with high rates of comorbidity with the disruptive behavior disorders. Findings contribute to an emerging literature on preschool DMDD, with implications for early childhood psychiatric assessment and clinical interventions.

Morphological and molecular features of astroblastoma, including BRAFV600E mutations, suggest an ontological relationship to other cortical-based gliomas of children and young adults.

BACKGROUND: Astroblastomas (ABs) are rare glial tumors showing overlapping features with astrocytomas, ependymomas, and sometimes other glial neoplasms, and may be challenging to diagnose. METHODS: We examined clinical, histopathological, and molecular features in 28 archival formalin-fixed, paraffin-embedded AB cases and performed survival analyses using Cox proportional hazards and Kaplan-Meier methods. RESULTS: Unlike ependymomas and angiocentric gliomas, ABs demonstrate abundant distinctive astroblastic pseudorosettes and are usually Olig2 immunopositive. They also frequently exhibit rhabdoid cells, multinucleated cells, and eosinophilic granular material. They retain immunoreactivity to alpha thalassemia/mental retardation syndrome X-linked, are immunonegative to isocitrate dehydrogenase-1 R132H mutation, and only occasionally show MGMT promoter hypermethylation differentiating them from many diffuse gliomas. Like pleomorphic xanthoastrocytoma, ganglioglioma, supratentorial pilocytic astrocytoma, and other predominantly cortical-based glial tumors, ABs often harbor the BRAFV600E mutation, present in 38% of cases tested (n = 21), further distinguishing those tumors from ependymomas and angiocentric gliomas. Factors correlating with longer patient survival included age less than 30 years, female gender, absent BRAFV600E , and mitotic index less than 5 mitoses/10 high-power fields; however, only the latter was significant by Cox and Kaplan-Meier analyses (n = 24; P = .024 and .012, respectively). This mitotic cutoff is therefore currently the best criterion to stratify tumors into low-grade ABs and higher-grade anaplastic ABs. CONCLUSIONS: In addition to their own characteristic histological features, ABs share some molecular and histological findings with other, possibly ontologically related, cortical-based gliomas of mostly children and young adults. Importantly, the presence of BRAFV600E mutations in a subset of ABs suggests potential clinical utility of targeted anti-BRAF therapy.

Suicidal thoughts and behaviors in psychiatrically referred young children.

Despite increased awareness of the prevalence and seriousness of mental health problems in early childhood, there have been few empirical studies of suicidal thoughts and behaviors in this age group. This study examined suicidal thoughts and behaviors in 360 preschool-aged children (ages 3 to 7 years) presenting to a psychiatric day treatment program. A semi-structured diagnostic interview (conducted with primary caregivers) was used to assess for child suicidal thoughts and behaviors and psychiatric disorders. Participating mothers also reported on their own psychological distress and family psychiatric history. Forty-eight children (13%) were reported to have suicidal thoughts and behaviors, with suicidal plans or attempts endorsed for 2-3% of the sample. Suicidal thinking and behavior was associated with older child age and with higher rates of concurrent depression, oppositional defiant disorder, and posttraumatic stress disorder in univariate analyses, with age and depression remaining as significant predictors in a multivariate logistic regression model. Findings suggest that suicidal thoughts and behaviors are a significant clinical concern for young children presenting with early psychopathology, particularly depression, with implications for early childhood psychiatric assessment and treatment.

Hand1 overexpression inhibits medulloblastoma metastasis.

Medulloblastoma (MB) is the most frequent malignant pediatric brain tumor. Current treatment includes surgery, radiation and chemotherapy. However, ongoing treatment in patients is further classified according to the presence or absence of metastasis. Since metastatic medulloblastoma are refractory to current treatments, there is need to identify novel biomarkers that could be used to reduce metastatic potential, and more importantly be targeted therapeutically. Previously, we showed that ionizing radiation-induced uPAR overexpression is associated with increased accumulation of ß-catenin in the nucleus. We further demonstrated that uPAR protein act as cytoplasmic sequestration factor for a novel basic helix-loop-helix transcription factor, Hand1. Among the histological subtypes classical and desmoplastic subtypes account for the majority while large cell/anaplastic variant is most commonly associated with metastatic disease. In this present study using immunohistochemical approach and patient data mining for the first time, we demonstrated that Hand1 expression is observed to be downregulated in all the subtypes of medulloblastoma. Previously we showed that Hand1 overexpression regulated medulloblastoma angiogenesis and here we investigated the role of Hand1 in the context of Epithelial-Mesenchymal Transition (EMT). Moreover, UW228 and D283 cells overexpressing Hand1 demonstrated decreased-expression of mesenchymal markers (N-cadherin, ß-catenin and SOX2); metastatic marker (SMA); and increased expression of epithelial marker (E-cadherin). Strikingly, human pluripotent stem cell antibody array showed that Hand1 overexpression resulted in substantial decrease in pluripotency markers (Nanog, Oct3/4, Otx2, Flk1) suggesting that Hand1 expression may be essential to attenuate the EMT and our findings underscore a novel role for Hand1 in medulloblastoma metastasis.

Active Duty Women's Perceptions of Breast-Feeding Support in the Military Setting.

BACKGROUND: The purpose of this study is to evaluate the current perceptions of breast-feeding support for active duty women serving in the U.S. Armed Forces. METHODS: An online survey based on the Workplace Breastfeeding Support Scale (WBSS) was used to collect data from active duty military mothers. Data were collected and analyzed using SPSS software to evaluate active duty women's perceptions of breast-feeding support in the military. RESULTS: 318 active duty women participated in the online survey. The average WBSS scores for active duty women was 50.20 (SD = 15.75). Comparing WBSS scores and branch of service, women in the Army had significantly lower WBSS scores (M = 45.85) then women in the Air Force (M = 53.96, p < 0.001). Enlisted women had significantly lower scores (M = 47.12) than officers (M = 54.62, p < 0.001). Also noted were significantly lower scores of active duty women who were Hispanic (M = 44.30) and women who had lower levels of education (M = 46.90, p = 0.006). CONCLUSIONS: The Department of Defense may be able to improve breast-feeding rates for all active duty mothers by implementing and adhering to lactation policies and focusing support efforts for enlisted women in all branches of service.

Adverse Events in Very Young Children Prescribed Psychotropic Medications: Preliminary Findings from an Acute Clinical Sample.

OBJECTIVE: The present study used the Pediatric Adverse Events Rating Scale (PAERS) to provide a systematic assessment of adverse events (AEs) related to psychotropic medication use in a clinical sample of young children attending a specialized, early childhood partial hospital program. Study goals were as follows: 1) To describe the frequency and types of specific psychotropic medication-related AEs experienced by very young children (ages 3-7 years) in an acute clinical sample, and 2) to identify the psychotropic medication(s) and/or class(es) associated with the highest frequency of AEs. METHODS: Participants were 158 children (118 males; ages 36-95 months, mean=66 months, SD=14.6 months) who presented to a hospital-based day treatment program for young children with severe emotional and behavioral problems, and were prescribed a psychotropic medication at any point during the hospitalization. Data on AEs related to psychotropic medication were collected using the PAERS from 2011 to 2014. RESULTS: The percentages of children who experienced one or more AEs attributed to a psychiatric medication ranged from 0 (sertraline, melatonin) to 41.2% (fluoxetine), with wide variability in the types AEs reported. The overall frequencies of events caused by a stimulant were similar across the two medications examined (21.4% and 27.7% for mixed amphetamine salts and methylphenidate, respectively), with mood-related difficulties and decreased appetite being the most common AEs reported. The frequencies of AEs caused by an α agonist were also similar across the two medications examined (9.8% and 17.2% for guanfacine and clonidine, respectively), with fatigue as the most commonly reported AE. With respect to the selective serotonin reuptake inhibitor (SSRI) class, there was a trend for fluoxetine to be associated with more AEs (41.2%) than sertraline (for which no AEs were reported). The most common AEs reported for fluoxetine were impulsivity and poor concentration. CONCLUSIONS: The data presented here support existing literature reporting differences in AEs between age groups. More rigorous studies are warranted to further examine the types and frequencies of AEs related to psychotropic medications in very young children.

Sleep Onset and Night Waking Insomnias in Preschoolers with Psychiatric Disorders.

This study examined the nature and prevalence of diagnostically defined sleep disorders, including Sleep Onset Insomnia (SOI) and Night Waking Insomnia (NWI), in a sample of 183 young children admitted to an early childhood psychiatric day treatment program. A semi-structured diagnostic interview, the Diagnostic Infant and Preschool Assessment, was used to assess for sleep and other psychiatric disorders. Daily sleep diaries and the Child Behavior Checklist were also examined. 41 % of children met criteria for a sleep disorder; 23 % met diagnostic criteria for SOI and 4 % met criteria for NWI, with an additional 14 % meeting criteria for both (SOI + NWI). Sleep-disordered children demonstrated longer latency to sleep onset, longer and more frequent night awakenings, less total sleep, and lower sleep efficiency than non-sleep disordered participants. Diagnosable sleep disorders, particularly SOI, were quite common in this acute clinical sample, exceeding previous estimates obtained in community and pediatric practice samples.

The pathologic spectrum of oculoleptomeningeal amyloidosis with Val30Gly transthyretin gene mutation in a postmortem case.

We report the clinical and postmortem pathologic features of a 60-year-old woman with oculoleptomeningeal amyloidosis with a Val30Gly transthyretin gene mutation. Unlike other forms of hereditary amyloidosis, this rare type displays amyloid deposition predominantly in the eyes and central nervous system. Our patient belongs to 1 of only 2 kindreds known to carry this transthyretin mutation. Previous reports focused on examination of the brain and spinal cord, largely ignoring postmortem examination of the eyes. In this case, autopsy examination revealed amyloid deposition in the leptomeninges surrounding the brain, spinal cord, and optic nerves. Subependymal amyloid deposits projecting into the lateral ventricles as well as amyloid deposition in the choroid plexus, retinal vessels, nerve fiber layer of the retina, and vitreous were observed. Amyloid was not identified elsewhere in the body. Awareness of this rare form of hereditary amyloidosis is crucial, given the substantial genetic and therapeutic implications of the diagnosis. Oculoleptomeningeal amyloidosis can be easily diagnosed during life with vitreous biopsy, as was the case in our patient.

Luminal subtypes predict improved survival following central nervous system metastasis in patients with surgically managed metastatic breast carcinoma.

CONTEXT: Metastatic breast cancer to the central nervous system (CNS) is second only to lung cancer metastasis to the CNS in frequency. Patients with triple-negative primary breast cancer and those with human epidermal growth factor receptor 2 (HER2)-positive primary breast cancer are at an increased risk for metastasis. Very little is known about predictive or prognostic variables once patients develop CNS metastases. Currently, therapeutic options are limited, with surgery generally offered primarily to those with solitary lesions. OBJECTIVES: To determine the influence of molecular subtypes of metastatic breast cancer on survival from the time of CNS metastasis and to aid in the prognostic stratification of these patients. DESIGN: We identified 59 cases of metastatic breast cancer to the CNS and analyzed them for various demographic and clinicopathologic parameters. Tumors were categorized into molecular subtypes using immunohistochemical methods: luminal A [estrogen receptor (ER⁺)/Ki67low], luminal B (ER⁺/Ki67 high), intrinsic HER2 (ER⁻/HER2⁺), and triple-negative. Survival after CNS metastasis for each group was plotted using a Kaplan-Meier curve, and multivariate analysis was performed. RESULTS: Patients with metastases from luminal tumors had a statistically significant survival advantage when compared with those of the triple-negative phenotype. Importantly, survival among patients with luminal A and luminal B tumors was not significantly different. Similarly, patient's age, histologic grade, and number of lesions did not contribute to determining outcomes. CONCLUSIONS: Estrogen receptor positivity (ie, luminal phenotype) of tumors appears to determine outcomes after development of metastases. In contrast, proliferation rate had little or no effect on the long-term survival. Understanding the biology of metastases can help stratify patients into prognostically meaningful categories and tailor treatment regimens for individual patients.