Reporting of social determinants of health in randomized controlled trials conducted in the pediatric intensive care unit.

Introduction: The influence of social determinants of health (SDOH) on access to care and outcomes for critically ill children remains an understudied area with a paucity of high-quality data. Recent publications have highlighted the importance of incorporating SDOH considerations into research but the frequency with which this occurs in pediatric intensive care unit (PICU) research is unclear. Our objective was to determine the frequency and categories of SDOH variables reported and how these variables were defined in published PICU randomized controlled trials (RCTs). Methods: We searched Medline, Embase, Lilacs, and Central from inception to Dec 2022. Inclusion criteria were randomized controlled trials of any intervention on children or their families in a PICU. Data related to study demographics and nine WHO SDOH categories were extracted, and descriptive statistics and qualitative data generated. Results: 586 unique RCTs were included. Studies had a median sample size of 60 patients (IQR 40-106) with 73.0% of studies including ≤100 patients and 41.1% including ≤50 patients. A total of 181 (181/586, 30.9%) studies reported ≥1 SDOH variable of which 163 (163/586, 27.8%) reported them by randomization group. The most frequently reported categories were food insecurity (100/586, 17.1%) and social inclusion and non-discrimination (73/586, 12.5%). Twenty-five of 57 studies (43.9%) investigating feeding or nutrition and 11 of 82 (13.4%) assessing mechanical ventilation reported baseline nutritional assessments. Forty-one studies investigated interventions in children with asthma or bronchiolitis of which six reported on smoking in the home (6/41, 14.6%). Discussion: Reporting of relevant SDOH variables occurs infrequently in PICU RCTs. In addition, when available, categorizations and definitions of SDOH vary considerably between studies. Standardization of SDOH variable collection along with consistent minimal reporting requirements for PICU RCT publications is needed.

Complete Remission of BCG-Refractory High-grade Bladder CIS with Pharmacologic Ascorbate and Mistletoe.

Context: Bladder cancer is the fourth-most-common cancer in males in the U.S., who develop about 90% of the high-grade, carcinoma in situ (CIS) of non-muscle involved disease (NMIBC). Smoking and occupational carcinogens are well-known causes. For females without known risk factors, bladder cancer can be regarded as a sentinel environmental cancer. It's also one of the costliest to treat due to its high rate of recurrence. No treatment innovations have occurred in nearly two decades; intravesical instillation of Bacillus Calmette-Guerin (BCG), an agent in short supply globally, or Mitomycin-C (MIT-C) is effective in about 60% of cases. Cases refractory to BCG and MIT-C often undergo cystectomy, a procedure with numerous impacts on life styles and potential complications. The recent completion of a small Phase I trial of mistletoe in cancer patients that have exhausted known treatments at Johns Hopkins provides corroboration of its safety, with 25 % showing no disease progression. Objective: The study examined the benefits of pharmacologic ascorbate (PA) and mistletoe for a nonsmoking female patient with an environmental history of NMIBC refractory to BCG, in a non-smoking female with exposures in childhood and early adult life to several known carcinogens, including ultrafine particulate air pollution, benzene, toluene, and other organic solvents, aromatic amines and engine exhausts, and possibly arsenic in water. Design: The research team performed an integrative oncology case study on pharmacologic ascorbate (PA) and mistletoe, both agents shown to activate NK cells, enhance growth and maturation of T-cells, and induce dose-dependent pro-apoptotic cell death, suggesting shared and potentially synergistic mechanisms. Setting: The study began at the University of Ottawa Medical Center in Canada with treatment continuing over six years at St. Johns Hospital Center in Jackson, Wyoming, and George Washington University Medical Center for Integrative Medicine, with surgical, cytological, and pathological evaluations at University of California San Francisco Medical Center. Participant: The patient in the case study was a 76-year-old, well-nourished, athletic, nonsmoking female with high-grade CIS of the bladder. Her cancer was considered to be a sentinel environmental cancer. Intervention: Intravenous pharmacologic ascorbate (PA) and subcutaneous mistletoe (three times weekly) and intravenous and intravesical mistletoe (once weekly) were employed for an 8-week induction treatment, using a dose-escalation protocol as detailed below. Maintenance therapy was carried out with the same protocol for three weeks every three months for two years. Results: The patient has experienced a cancer-free outcome following 78 months of treatments that incorporated intravesical, intravenous, and subcutaneous mistletoe; intravenous PA; a program of selected nutraceuticals; exercise; and other supplementary treatments. Conclusions: This study is the first reported instance of combined treatments to achieve complete remission for high-grade NMIBC refractory to BCG and MIT-C, using intravesical, subcutaneous, and intravenous mistletoe and intravenous PA. It includes pharmacological information on possible mechanisms. In light of the global shortage of BCG, the high proportion of cases refractory to BCG and MIT-C, the unproven use of costly off-label pharmaceuticals, such as gemcitabine, and the relative cost-effectiveness of mistletoe and PA, clinicians should give serious consideration to employing these combined functional medicine treatments for BCG- and MIT-C-refractory NMIBC. Further research is needed with additional patients that can advance our understanding, including standardization of methods for systematically evaluating combined therapies-blinded and non-blinded, nomenclature regarding mistletoe preparation, doses, concentrations, regimes of administration, lengths of treatment, targeted cancer types, and other aspects.

Australian guidelines for the management of children with achondroplasia.

Achondroplasia is the most common form of skeletal dysplasia. In addition to altered growth, children and young people with achondroplasia may experience medical complications, develop and function differently to others and require psychosocial support. International, European and American consensus guidelines have been developed for the management of achondroplasia. The Australian focused guidelines presented here are designed to complement those existing guidelines. They aim to provide core care recommendations for families and clinicians, consolidate key resources for the management of children with achondroplasia, facilitate communication between specialist, local teams and families and support delivery of high-quality care regardless of setting and geographical location. The guidelines include a series of consensus statements, developed using a modified Delphi process. These statements are supported by the best available evidence assessed using the National Health and Medicine Research Council's criteria for Level of Evidence and their Grading of Recommendations Assessment, Development and Evaluation (GRADE). Additionally, age specific guides are presented that focus on the key domains of growth, medical, development, psychosocial and community. The guidelines are intended for use by health professionals and children and young people with achondroplasia and their families living in Australia.

Recommendations for procurement of starting materials by apheresis for advanced therapy medicinal products.

Activities involved in the production of certain advanced therapy medicinal products (ATMPs) require standardized approaches to mononuclear cell procurement to ensure the highest product quality, safety and process efficiency. These aims must be achieved while meeting regulatory and accreditation requirements for the procurement of mononuclear cells as starting materials. Mononuclear cells constitute the starting materials for many ATMPs, and this article sets out recommendations for procurement by clinical apheresis, addressing the variation among existing working practices and different manufacturers' requirements that currently poses a challenge when managing multiple different protocols.

Medical complications in children with achondroplasia.

AIM: To determine the rates of medical investigations, complications, interventions, and outcomes in children with achondroplasia. METHOD: Children and adolescents with achondroplasia born between 2000 and 2019, aged between 0 and 18 years of age, and seen at The Children's Hospital at Westmead skeletal dysplasia clinic were included. Data were collected retrospectively from clinical records. Standard descriptive statistics were used for analysis. RESULTS: The study included 108 participants, 58 males and 50 females. Ninety-nine participants (91.7%) entered the study at birth. The other nine (8.3%) participants entered the study after birth (mean age = 2 years 4 months, SD = 1 year 8 months). The median age of exit from the study was 8 years 8 months (IQR = 8 years 9 months) with a median follow-up of 8 years 8 months (IQR = 8 years 9 months). Fifty-two (48%) participants presented with craniocervical stenosis, 15 (13.9%) with hydrocephalus, 66 (61.1%) with hearing impairment, 44 (40.7%) with sleep-disordered breathing, 46 (42.6%) with lower-limb malalignment, 24 (22.2%) with thoracolumbar kyphosis, 10 (9.3%) with symptomatic spinal stenosis, 12 (11.1%) with obesity, and 16 (14.8%) who had at least one admission for respiratory illness. Two children died during the study period. INTERPRETATION: We report contemporary rates of medical complications in an Australian population of children with achondroplasia. Recommendations for surveillance in clinical practice are discussed. This information will help guide clinicians with their expectant management of achondroplasia and provide prognostic information to the families of children with achondroplasia.

Clinical research reactivation during the COVID-19 pandemic: An academic center process and lessons for the future.

Background: Clinical research is a central mission of the University of Colorado Anschutz Medical Campus (CU-Anschutz). On March 18, 2020, due to rising COVID-19 rates and personal protective equipment (PPE) shortages, an emergency approval process for critical research essential to the care and safety of patients, including COVID-19 trials, was enacted. All other clinical research studies requiring face-to-face visits were placed on hold to protect participant and staff safety. Methods: A clinical research TaskForce was rapidly assembled, consisting of a cross- section of campus clinical research operations leaders, including affiliate hospitals. This group developed a guidance document and process where the primary prioritization factor was positive therapeutic benefit/risk (Groups 2-5). A REDCap form demarcating items including research visit types and safety plans was designed. A separate Space Plan Committee approval was required to gauge environmental health and safety. Results: A total of 654 protocols were approved over 31 weeks using this process. Group 2 review and approvals occurred within 5 days of campus reactivation, and 65 days after original clinical research hold. Groups 3 through 5 were opened for submission and review in a phased approach. The majority proactively submitted IRB protocol amendments to minimize face-to-face participant/staff contact. There were no cases of COVID-19 outbreak in research participants. Conclusion: Clinical research reactivation was rapidly implemented in a transparent, collaborative, broadly supported, and efficient process of staged reactivation while prioritizing the health and safety of participants and staff at CU-Anschutz. This model is practical and easily generalizable to other medical research campuses.

Inflammatory cytokines, placental pathology, and neurological outcomes in infants born to preterm preeclamptic mothers.

Preeclampsia is both a vascular and inflammatory disorder. Since the placenta is a conduit for fetal development, preeclampsia should be a presumed cause of adverse infant outcomes. Yet, the relationship of placental pathology, inflammation and neurological outcomes after preeclampsia are understudied. We prospectively examined a cohort of maternal-infant dyads with preeclampsia for maternal inflammatory cytokines at time of preeclampsia diagnosis and delivery, and fetal cord blood cytokines (IL-1ß, IL-6, IL-8, and TNF-α). Placentas were analyzed for inflammatory and vascular pathologies. Neurodevelopmental assessment of infants utilizing the Pediatric Stroke Outcome Measure (PSOM) was conducted at 6-month corrected gestational age. Eighty-one maternal-newborn dyads were examined. Worse neurological outcomes were not associated with elevated maternal / fetal cytokines. Early preterm birth (gestational age ≤ 32 weeks) was associated with worse neurological outcomes at 6-months regardless of maternal/ fetal cytokine levels, placental pathology, or cranial ultrasound findings (OR 1.70, [1.16-2.48], p = 0.006). When correcting for gestational age, elevated IL-6 approached significance as a predictor for worse developmental outcome (OR 1.025 [0.985-1.066], p = 0.221). Pathological evidence of maternal malperfusion and worse outcomes were noted in early preterm, although our sample size was small. Our study did not demonstrate an obvious association of inflammation and placental pathology in preeclampsia and adverse neurodevelopmental outcome at 6-month corrected age but does suggest maternal malperfusion at earlier gestational age may be a risk factor for worse outcome.

Antithrombin deficiency: A pediatric disorder.

INTRODUCTION: Hereditary antithrombin (AT) deficiency is an autosomal dominant thrombophilic disorder. Guidelines do not support routine testing of children based on personal or familial thrombosis. AIM: To investigate clinical, genetic and laboratory profiles of AT deficient children and their affected family members. MATERIALS AND METHODS: Data were analyzed from a prospective cohort of pediatric patients with AT deficiency. The SERPINC1 gene was sequenced for all individuals with available DNA. AT, thromboelastography (TEG), calibrated automated thrombogram (CAT), D-dimer, thrombin-antithrombin complex (TAT) and factor VIII activity were performed on patient samples. RESULTS: Thirty-six individuals from 11 families had AT deficiency (activities 45-70 U/dL) with incident thrombosis in 13 children and 10 adults (64% overall). Three neonates presented with middle cerebral artery and/or aortic occlusions with inferior vena cava and cerebral or renal vein thromboses in 2 of the 3. Two pre-pubertal children were symptomatic, one with cerebral venous sinus thrombosis who suffered recurrent arterial and venous thrombi. Both Type I and Type II AT deficiencies conferred a high severity of thromboses. Heterozygous SERPINC1 mutations were identified in seven families; three were novel, resulting in missense, splice site and frameshift alterations. Thrombin generation (CAT) was increased in all asymptomatic affected patients including 9 children and 1 adult. CONCLUSIONS: Genetic AT deficiency often presents in infants and children, warranting laboratory evaluation based on personal and family history. Increased thrombin generation was detected in all asymptomatic children and adults, suggesting a possible role in detecting and monitoring individuals at risk for thrombosis.

Childhood prevalence of achondroplasia in New South Wales and the Australian Capital Territory, Australia.

The aim of this study was to estimate the childhood prevalence of achondroplasia, trends over time in birth prevalence, and age at diagnosis in Australia. Children born between 1990 and 2019 with a clinical and radiological and/or molecular diagnosis of achondroplasia were identified from a tertiary hospital servicing New South Wales (NSW) and the Australian Capital Territory (ACT) and compared with population data from the Australian Bureau of Statistics. Childhood prevalence of achondroplasia, based on children ≤19 years of age and resident in NSW/ACT on June 30, 2019 (n = 109), was 5.2 per 100,000. A total of 127 individuals with achondroplasia were born in 1990-2019 in NSW/ACT. Birth prevalence rates increased across birth decades, from 3.3 per 100,000 live births in 1990-1999 to 5.3 per 100,000 in 2010-2019 (p < 0.0001). Median age at diagnosis decreased to 17 days in 2010-2019 compared with 30 days in 1990-1999 (p = 0.035), although the overall decreasing trend across consecutive decades did not reach statistical significance. This is the first study to show a rising birth prevalence rate for achondroplasia in Australia with a concurrent decreasing age at diagnosis, both of which were statistically significant after 2 decades.

Differential expression of GluN2 NMDA receptor subunits in the dorsal horn of male and female rats.

N-methyl-D-aspartate receptors (NMDARs) are excitatory ionotropic glutamate receptors expressed throughout the CNS, including in the spinal dorsal horn. The GluN2 subtypes of NMDAR subunit, which include GluN2A, GluN2B, and GluN2D in the dorsal horn, confer NMDARs with structural and functional variability, enabling heterogeneity in synaptic transmission and plasticity. Despite essential roles for NMDARs in physiological and pathological pain processing, the distribution and function of these specific GluN2 isoforms across dorsal horn laminae remain poorly understood. Surprisingly, there is a complete lack of knowledge of GluN2 expression in female rodents. We, therefore, investigated the relative expression of specific GluN2 variants in the dorsal horn of lumbar (L4/L5) spinal cord from both male and female rats. In order to detect synaptic GluN2 isoforms, we used pepsin antigen-retrieval to unmask these highly cross-linked protein complexes. We found that GluN2B and GluN2D are preferentially localized to the pain-processing superficial regions of the dorsal horn in males, while only GluN2B is predominantly localized to the superficial dorsal horn of female rats. The GluN2A subunit is diffusely localized to neuropil throughout the dorsal horn of both males and females, while GluN2B and GluN2D immunolabelling are found both in the neuropil and on the soma of dorsal horn neurons. Finally, we identified an unexpected enhanced expression of GluN2B in the medial division of the superficial dorsal horn, but in males only. These sex-specific localization patterns of GluN2-NMDAR subunits across dorsal horn laminae have significant implications for the understanding of divergent spinal mechanisms of pain processing.

Managing the risks and benefits of clinical research in response to a pandemic.

Introduction: The coronavirus disease 2019 (COVID-19) created major disruptions at academic centers and healthcare systems globally. Clinical and Translational Science Awards (CTSA) fund hubs supported by the National Center for Advancing Translational Sciences provideinfrastructure and leadership for clinical and translational research at manysuch institutions. Methods: We surveyed CTSA hubs and received responses from 94% of them regarding the impact of the pandemic and the processes employed for the protection of research personnel and participants with respect to the conduct of research, specifically for studies unrelated to COVID-19. Results: In this report, we describe the results of the survey findings in the context of the current understanding of disease transmission and mitigation techniques. Conclusions: We reflect on common practices and provide recommendations regarding lessons learned that will be relevant to future pandemics, particularly with regards to staging the cessation and resumption of research activities with an aim to keep the workforce, research participants, and our communities safe in future pandemics.

Clinic Follow up and Neurological Disability in Children Following Pregnancies Complicated by Preterm Rupture of Membranes and Preeclampsia.

Context: Preeclampsia and preterm premature rupture of membranes (PPROM) have been associated with perinatal brain injury. Despite a strong understanding of the relationships between preterm birth and neurologic deficits, and between PPROM and preeclampsia and preterm birth, the relationship between PPROM and preeclampsia and neurologic disability is not well characterized. Objective: We compared trends in neurologic deficits in children born to mothers with these conditions and described differences in patient characteristics among follow up visit attendance. Methods: We conducted a prospective cohort study of women with preeclampsia or PPROM. Neurologic deficits were assessed with the Pediatric Stroke Outcome Measure at follow up visits through age 10 years. Eighty nine of the 178 women enrolled completed at least one follow up. Results: Among children born >32 weeks, PPROM showed higher left and right sided sensorimotor deficits at initial follow (p=0.045, p=0.01). In children born ≤ 32 weeks, preeclampsia had higher language production deficits at 3 year follow up (p=0.05).Sensorimotor deficits were greater and sustained in PPROM. Language production deficits were predominant among after 2 years of age in preeclampsia. Racial disparities were found in clinic attendance rates, with Black families most affected. Conclusion: Differences in neurodevelopmental patterns suggest differences in underlying neuronal injuries. Neurologic assessment should occur routinely throughout early childhood to detect delayed deficits after PPROM and preeclampsia and ensure inclusion of underserved or at risk populations.

The effects of socioeconomic status on baseline neurocognitive testing scores.

Baseline neurocognitive testing has been recommended to provide a more accurate representation of the pre-concussion cognitive status of individual athletes. Socioeconomic status is not typically controlled for when obtaining baseline scores, which may lead to inaccurate findings if post-injury scores are compared to normative data. Understanding the role of socioeconomic status in baseline testing is important for the accurate analysis of test scores and proper evaluation of patients if individualized baseline data are not available. Our purpose was to investigate the effects of socioeconomic status, as determined by eligibility for free or reduced cost lunch on baseline neurocognitive test scores in secondary school athletes. 1,788 secondary school athletes (females = 778, males = 1,010, age = 14.96 ± 1.11 years, height = 171.25 ± 17.83 cm, mass = 66.82 ± 21.63 kg) completed the Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) upon starting scholastic athletics. ImPACT components (symptom severity scores and composite scores of verbal memory, visual memory, visual motor speed, and reaction time) served as the dependent variables. School administration coded free or reduced cost lunch eligibility (N = 1255 not eligible, N = 563 eligible) for each participant (group), which served as the independent variable. Free or reduced cost lunch eligibility significantly altered the combined dependent variables (multivariate F5,1780=14.41, p < .001, ɳ2 = .04) when sex and age were controlled. Follow up ANOVAs showed that participants eligible for free or reduced cost lunch scored significantly worse on verbal memory (F1,1784 = 24.81, p < .001, ɳ2 = .01), visual memory (F1,1784 = 24.90, p < .001, ɳ2 = .01), and visual motor speed (F1,1784 = 50.54, p < .001, ɳ2 = .03). In addition, slower reaction times (F1,1784 = 35.10, p < .001, ɳ2 = .02) and higher symptom severity scores (F1,1784 = 10.37, p < .01, ɳ2 = .01) were observed in those eligible for free or reduced cost lunch. If normative data are used instead of individual baselines, potential modifiers such as socioeconomic status should be taken into account when analyzing concussion scores to provide accurate diagnoses.

Treatment and outcome of childhood cerebral sinovenous thrombosis.

OBJECTIVE: To test our hypothesis that anticoagulation is associated with better neurologic outcomes in childhood cerebral sinovenous thrombosis (CSVT), we analyzed treatment and outcomes in a population of 410 children from the International Pediatric Stroke Study (IPSS). METHODS: We included patients enrolled in the IPSS registry with a diagnosis of CSVT at age >28 days with radiologic confirmation, in isolation or with concomitant arterial ischemic stroke. The primary outcome was the neurologic status at discharge. We defined unfavorable outcome as severe neurologic impairment or death at discharge. The Pediatric Stroke Outcome Measure was used for long-term outcome in those with follow-up. Predictors of anticoagulation use and outcome were analyzed by logistic regression. RESULTS: Most children (95%) had identifiable risk factors, and 82% received anticoagulation. Shift analysis demonstrated better outcomes at discharge in children who were anticoagulated, and this persisted with longer-term outcomes. In multivariable analysis, anticoagulation was significantly associated with favorable outcomes (adjusted odds ratio [aOR] unfavorable 0.32, p = 0.007) whereas infarct was associated with unfavorable outcome (aOR unfavorable 6.71, p < 0.001). The trauma/intracranial surgery was associated with a lower odds of anticoagulation use (aOR 0.14, p < 0.001). CONCLUSIONS: Within the IPSS registry, children with risk factors of trauma or intracranial surgery were less likely to receive anticoagulation for CSVT. Anticoagulation was associated with a lower odds of severe neurologic impairment or death at hospital discharge, but this finding is limited and needs further confirmation in randomized, controlled, prospective studies.

Association between Pregnancy and Cervical Artery Dissection.

OBJECTIVE: We wanted to determine whether pregnancy is associated with cervical artery dissection. METHODS: We performed a case-control study using claims data from all nonfederal emergency departments and acute care hospitals in New York and Florida between 2005 and 2015. Cases were women 12-42 years of age hospitalized with cervical artery dissection, defined using validated diagnosis codes for carotid/vertebral artery dissection. Controls were women 12-42 years of age with a primary diagnosis of renal colic. Cases and controls were matched 1:1 on age, race, insurance, income, state, and visit year. The exposure variable was pregnancy, defined as labor and delivery within 90 days before or 6 months after the index visit. Logistic regression was used to compare the odds of pregnancy between cases and controls. We performed a secondary cohort-crossover study comparing the risk of cervical artery dissection during pregnancy versus the same time period 1 year later. RESULTS: Pregnancy was twice as common among 826 women with cervical artery dissection compared with the 826 matched controls with renal colic (odds ratio, 2.5; 95% confidence interval [CI], 1.3-4.7). In our secondary analysis, pregnancy was associated with a higher risk of cervical artery dissection (incidence rate ratio [IRR], 2.2; 95% CI, 1.3-3.5), with the heightened risk limited to the postpartum period (IRR, 5.5; 95% CI, 2.6-11.7). INTERPRETATION: Pregnancy, specifically the postpartum period, was associated with hospitalization for cervical artery dissection. Although these findings might in part reflect ascertainment bias, our results suggest that arterial dissection is one mechanism by which pregnancy can lead to stroke. ANN NEUROL 2020;88:596-602.

Successful treatment of hemorrhagic brainstem cavernous malformation with hematoma evacuation and postoperative propranolol.

In this case, we describe an evident hemorrhagic brainstem cavernous malformation successfully treated with a planned sequence of surgical evacuation of the hematoma followed by postoperative propranolol therapy. In contrast to common practice, the cavernoma itself was not resected. A nearly 3-year-old male presented with altered mental status, gait disturbance, and facial palsy. CT and MRI demonstrated a large acute pontine hematoma. A large nearby vein suggested cavernous malformation. He was initially treated conservatively but a repeat CT scan demonstrated further expansion of hematoma and he was taken emergently to the OR. Due to the sensitive location of the hematoma in the pons, we planned to evacuate the hematoma without resecting any of the presumed cavernoma. Instead, we planned to treat the cavernoma with propranolol. Postoperatively, the patient's condition improved and was still improving at hospital discharge 2 weeks later. Six-month follow-up MRI showed no cavernoma with only hemosiderin at the site of the evacuated hematoma. This is the first reported case of a hemorrhagic brainstem cavernous malformation treated with a planned sequence of hematoma evacuation followed by propranolol without an attempt to resect the cavernoma.

Subpial Hemorrhage of the Neonate.

Background and Purpose- Subpial hemorrhage of the neonate is a rare stroke subtype reported in few case series. Birth trauma and coagulopathy are commonly proposed etiologies. We evaluated our subpial hemorrhage of the neonate patient cohort to expand current understanding Methods- Cases of subpial hemorrhage of the neonate were identified by keyword searches of the institutional database. The medical records and magnetic resonance imagings were reviewed. Results- Seventeen cases were identified. Assisted delivery occurred in 12% of cases, and acute coagulation abnormalities occurred in 77%. Subpial hemorrhage of the neonate was located in the temporal lobe in 82%, with cytotoxic edema and medullary vein congestion and thrombosis subjacent to the hemorrhages in 100% and 76% of cases, respectively. Neurological disability was present in 44% of survivors. Three patients had chronic coagulation abnormalities. Conclusions- In our cohort, clinical findings supporting a potential relationship with birth trauma were infrequent. The imaging findings suggest a nonarterial, deep venous pattern of hemorrhagic ischemia.

Children with post-stroke epilepsy have poorer outcomes one year after stroke.

Background Epilepsy is a common complication of pediatric stroke. Aim In this study, we aim to measure the association between epilepsy and neurologic outcome after childhood arterial ischemic stroke. Methods Prospective cohort study of children (29 days-19 years) enrolled after an acute arterial ischemic stroke at 21 international pediatric stroke centers and followed to identify epilepsy. One year post-stroke, outcomes were scored using the examination-based Pediatric Stroke Outcome Measure (range = 0-10); higher values reflect greater disability. Ordinal logistic regression was used to measure the association of Pediatric Stroke Outcome Measure scores (categorized as 0-1, 1.5-3, 3.5-6, 6.5-10) with epilepsy. Results Investigators enrolled 86 children (median age = 6.1 years, interquartile range (IQR) = 1.4-12.2 years) with acute stroke. At 1 year, 18/80 (23%) remained on an anticonvulsant including 8/80 (10%) with epilepsy. Among the 70 with Pediatric Stroke Outcome Measure scored, the median was 0.5 (IQR = 0-1.5) for children without epilepsy ( n = 63), and 6 (IQR = 0.5-10) for children with epilepsy ( n = 7). In univariable analyses, poorer 1-year outcome was associated with middle cerebral artery stroke, cortical infarcts, hemorrhagic transformation, hospital disposition not to home, and epilepsy. In multivariable analysis, middle cerebral artery stroke (odds ratio (OR) = 4.9, 95% confidence intervals (CI) = 1.1-21.3) and epilepsy (OR = 24.1, CI = 1.5-380) remained associated with poorer outcome. Conclusions Children who developed epilepsy during the first year post-stroke had poorer neurologic outcomes than those without epilepsy.

Optimizing carbapenem use through a national quality improvement programme.

Background: Concern about increasing carbapenem and piperacillin/tazobactam use led the Scottish Antimicrobial Prescribing Group (SAPG) to develop national guidance on optimal use of these agents, and to implement a quality improvement programme to assess the impact of guidance on practice. Objectives: To evaluate how SAPG guidance had been implemented by health boards, assess how this translated into clinical practice, and investigate clinicians' views and behaviours about prescribing carbapenems and alternative agents. Methods: Local implementation of SAPG guidance was assessed using an online survey. A bespoke point prevalence survey was used to evaluate prescribing. Clinicians' experience of using carbapenems and alternatives was examined through semi-structured interviews. National prescribing data were analysed to assess the impact of the programme. Results: There were greater local restrictions for carbapenems than for piperacillin/tazobactam. Laboratory result suppression was inconsistent between boards and carbapenem-sparing antibiotics were not widely available. Compliance with local guidelines was good for meropenem but lower for piperacillin/tazobactam. Indication for use was well documented but review/stop dates were poorly documented for both antibiotics. Decisions to prescribe a carbapenem were influenced by local guidelines and specialist advice. Many clinicians lacked confidence to de-escalate treatment. Use of both antibiotics decreased during the course of the programme. Conclusions: A multifaceted quality improvement programme was used to gather intelligence, promote behaviour change, and focus interventions on the use of carbapenems and piperacillin/tazobactam. Use of these antimicrobials decreased during the programme-a trend not seen elsewhere in Europe. The programme could be generalized to other antimicrobials.

An RNAi-Based Candidate Screen for Modifiers of the CHD1 Chromatin Remodeler and Assembly Factor in Drosophila melanogaster.

The conserved chromatin remodeling and assembly factor CHD1 (chromodomains, helicase, DNA-binding domain) is present at active genes where it participates in histone turnover and recycling during transcription. In order to gain a more complete understanding of the mechanism of action of CHD1 during development, we created a novel genetic assay in Drosophila melanogaster to evaluate potential functional interactions between CHD1 and other chromatin factors. We found that overexpression of CHD1 results in defects in wing development and utilized this fully penetrant and reliable phenotype to conduct a small-scale RNAi-based candidate screen to identify genes that functionally interact with chd1 in vivo. Our results indicate that CHD1 may act in opposition to other remodeling factors, including INO80, and that the recruitment of CHD1 to active genes by RTF1 is conserved in flies.