A Cross-Sectional Comprehensive Assessment of the Profile and Burden of Non-motor Symptoms in Relation to Motor Phenotype in the Nigeria Parkinson Disease Registry Cohort.

BACKGROUND: Data on non-motor symptoms (NMS) in black Africans with Parkinson's disease (PD) are sparse. OBJECTIVE: To describe the profile of NMS in the Nigeria PD Registry (NPDR) cohort and explore the relationship between NMS and PD motor phenotype. METHODS: We conducted a cross-sectional study of the frequency and burden of NMS, based on the non-motor symptoms scale (NMSS) and the Chaudhuri method respectively in our cohort. Baseline demographics, disease characteristics (Hoehn and Yahr stage, MDS-UPDRS total score and Part III motor score), motor phenotype (based on Stebbin et al's algorithm), and levodopa equivalent daily dose (LEDD) were documented. RESULTS: Data are presented for 825 PD whose mean age at study was 63.7 ± 10.1 years, female sex-221 [26.8%] while median PD duration was 36 months. PD phenotypes included tremor-dominant 466 (56.5%), postural instability and gait disorder (PIGD) 259 (31.4%), and indeterminate 100 (12.1%). 82.6% were on treatment (median LEDD of 500 mg/24 hours). 804 (97.5%) endorsed at least 1 NMS. The median NMSS score was 26.0 while subscores for urinary and sexual function domains were significantly higher in males (P < 0.05). PIGD-PD had more frequent NMS and higher frequency of severe/very severe NMSS burden (P = 0.000 for both). Nocturia and fatigue were the most prevalent NMS overall and across motor subtypes. PIGD phenotype and total UPDRS scores were the independent determinants of NMSS scores (P = 0.000). CONCLUSION: The profile and burden of NMS, and association with motor subtype in our black African cohort is largely similar to descriptions from other populations.

The Nigeria Parkinson Disease Registry: Process, Profile, and Prospects of a Collaborative Project.

BACKGROUND: Clinical disease registries are useful for quality improvement in care, benchmarking standards, and facilitating research. Collaborative networks established thence can enhance national and international studies by generating more robust samples and credible data and promote knowledge sharing and capacity building. This report describes the methodology, baseline data, and prospects of the Nigeria Parkinson Disease Registry. METHODS: This national registry was established in November 2016. Ethics approval was obtained for all sites. Basic anonymized data for consecutive cases fulfilling the United Kingdom Parkinson's Disease Brain Bank criteria (except the exclusion criterion of affected family members) are registered by participating neurologists via a secure registry website (www.parkinsonnigeria.com) using a minimal common data capture format. RESULTS: The registry had captured 578 participants from 5 of 6 geopolitical zones in Nigeria by July 2019 (72.5% men). Mean age at onset was 60.3 ± 10.7 years; median disease duration (interquartile range) was 36 months (18-60.5 months). Young-onset disease (<50 years) represented 15.2%. A family history was documented in 4.5% and 7.8% with age at onset <50 and ≥ 50, respectively. The most frequent initial symptom was tremor (45.3%). At inclusion, 93.4% were on treatment (54.5% on levodopa monotherapy). Per-capita direct cost for the registry was $3.37. CONCLUSIONS: This is the first published national Parkinson's disease registry in sub-Saharan Africa. The registry will serve as a platform for development of multipronged evidence-based policies and initiatives to improve quality of care of Parkinson's disease and research engagement in Nigeria. © 2020 International Parkinson and Movement Disorder Society.

Air quality biomonitoring of trace elements in the metropolitan area of Huancayo, Peru using transplanted Tillandsia capillaris as a biomonitor.

The air quality and distribution of trace elements in a metropolitan area of the Peruvian Andes were evaluated using transplanted epiphytic Tillandsia capillaris as biomonitors. Biomonitors were collected from the non-contaminated area and exposed to five sites with different types of contamination for three months in 2017. After exposure, the content of twenty-one elements were determined by ICP-MS analysis. Datasets were evaluated by one-way ANOVA, exposed-to-baseline (EB), hierarchical cluster analysis (HCA) and principal component analysis (PCA). Results showed significant differences among sampling sites for several elements. According to EF ratios for Ba, Cr, Cu, Pb, Sb, and Zn EB ratios value greater than 1.75 were found around urban areas, indicating anthropogenic influence, which can be attributed to vehicular sources. The highest values of As and Cd were found in areas of agricultural practices, therefore their presence could be related to the employment of agrochemicals (pesticides, herbicides, and phosphate fertilizers). HCA shows that most elements come from vehicular sources and lower from agricultural and natural sources.

Assembly of Short-Chain Amphiphilic Homopolymers into Well-Defined Particles.

Linear homopolymers of norbornene (NBE) derivatives equipped with short-chain alcohol pendant groups were prepared by ring-opening metathesis polymerization (ROMP) and subsequently assembled into well-defined structures in alcohol solvents. The ratios of hydrophobic carbons and hydrophilic alcohol groups at the repeating monomeric unit in these short-chain amphiphilic polymers were found to play an important role in determining the size and distribution of the final globular structures. Unlike the assembly of other linear homo- and copolymers possessing long-chain amphiphilicity, NBE-based linear polymers were readily transformed into spherical particles with a layered conformation, whose sizes range from a few hundred nanometers to micrometers with narrow distributions, simply by controlling the concentration and molecular weights of the linear homopolymers without using any surfactants. In addition, the degree of the intermolecular forces with solvents (e.g., solvation) possessing different surface tensions and polarities highly affected the final diameter and distribution of the polymer particles, implying the importance of the selection of a proper solvent to regulate their structural features. As such, understanding the assembly of these types of short-chain homopolymers into uniform particles can allow for regulating the transformation of diverse linear amphiphilic polymers into precisely controlled structures for various applications.

Juvenile systemic lupus erythematosus presenting as pancarditis.

BACKGROUND: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with marked variation in its clinical presentation. Juvenile SLE (jSLE) accounts for 15-20% of all cases and is diagnosed when SLE manifests before 18 years of age. Pancarditis is a rare complication of SLE, regardless of age of disease onset. CASE PRESENTATION: We report a case of jSLE in a 15 year old Caucasian female presenting with an acute episode of pancarditis and multiorgan dysfunction who was successfully treated with systemic corticosteroids and cyclophosphamide. CONCLUSION: Pancarditis can be a presenting feature of jSLE which was previously unreported. A high index of suspicion for severe cardiac involvement is required at all stages of disease.

Congenital Atrial Haemangioma

Introduction Primary cardiac tumours are rare. We report the first known case of congenital cardiac haemangioma in Ireland. Case A neonate presented with symptoms arising from a congenital atrial haemangioma on day three of life. The mass was successfully excised via median sternotomy and bicaval cannulation for cardiopulmonary bypass. The patient was discharged day ten postoperatively and remained well at one year follow-up. Discussion The degree of debulking surgery required varies depending on tumour type. This report serves to aid clinicians in accurately suspecting, investigating and diagnosing patients with cardiac tumours.

Cyanotic Congenital Heart Disease Modes of Presentation and Prenatal Detection

Prenatal detection of structural congenital heart disease (CHD) optimises cardiovascular stability pre-operatively and post-operative outcomes. We compared prenatal detection rates of critical CHD in units offering universal fetal anomaly scans with those offering imaging to selected women. One hundred and thirteen infants met inclusion criteria. The overall pre-natal detection rate for critical CHD was 57% of liveborn infants. It was 71% (57/80) in hospitals who offered a universal anomaly scan and 29% (9/31) in centres offering a limited service. Postnatal diagnosis was associated with PICU admission (p=0.016) and preoperative mechanical ventilation (p=0.001). One-year mortality was 10 fold higher in the postnatally diagnosed group 15% vs 1.55% (p=0.0066). There is a significant disparity between centres offering universal anomaly versus selective screening. Prenatal detection confers advantage in terms of pre-operative stability and one year survival. Failure to deliver an equitable service exposes infants with CHD to avoidable risk.

The utility of routine echocardiography in newborn infants with a persistent oxygen requirement

In the era of antenatal screening for congenital heart disease (CHD), infants presenting with an undiagnosed significant CHD are rare. However, term infants admitted with an initial diagnosis of TTN and a prolonged oxygen requirement often undergo an echocardiogram. We aimed to assess whether this practice yields any additional cases of undiagnosed CHD. We performed a retrospective chart review over a three year period [2013 ­ 2015] of term (> 36 weeks) infants admitted to the NICU for ≥ 5 days with a diagnosis of TTN and received an echocardiogram. The presence of CHD on the echocardiogram was assessed. Forty-seven infants were enrolled. The median age of echocardiogram was day four [2 ­ 8]. No infant had a diagnosis of significant CHD on the postnatal echocardiogram. A small muscular VSD was identified in two infants. Routine echocardiography for this cohort of infants to rule out major CHD appears to be unwarranted.

A conservative treatment of patent ductus arteriosus in very low birth weight infants.

BACKGROUND: Treatment of the patent ductus arteriosus (PDA) in the preterm infant remains contentious. There are numerous options of the PDA management from early targeted treatment, late (symptomatic) treatment to no treatment at all. AIMS: To evaluate a three different PDA management approaches in very low birth weight (VLBW) infants. STUDY DESIGN: A retrospective observational time series study of three cohorts of VLBW infants born between 2004 and 2011. SUBJECTS: Infants in Symptomatic Treatment Group (STG) were echocardiographically evaluated when clinical signs suggestive of a PDA were present and treated if a haemodynamically significant PDA was confirmed. Early Targeted Group (ETG) underwent echocardiography within the first 48h and infants received ibuprofen if a large PDA was present. Conservative Treatment Group (CTG) was screened by echocardiography on day seven of life; patients with PDA were managed with increased positive end expiratory pressure and fluid restriction as a first line intervention. OUTCOMES: The primary outcome was medical and surgical treatment in the three time periods. Secondary outcomes included mortality, severe periventricular and intraventricular haemorrhage, respiratory distress syndrome and chronic lung disease. RESULTS: There were 138 infants diagnosed with PDA; 52 infants in STG, 52 infants in ETG and 34 infants in CTG. Ibuprofen therapy and ligation were less frequent in CTG. There was significantly decreased incidence of chronic lung disease in CTG compared to STG (18% vs. 51%; p=0.003) and to ETG (18% vs. 46%; p=0.02). There was no difference in the other short term outcomes. CONCLUSION: Conservative treatment of persistent ductus arteriosus in VLBW infants is a feasible option and future randomized trials of conservative management are warranted.

Supportive behaviors in adolescent romantic relationships moderate adrenocortical attunement.

This study investigated dyadic adrenocortical attunement within adolescent romantic relationships. An ethnically diverse sample (42% Latino) of adolescent heterosexual dating couples (N=91 dyads, Mage=16.5 years, SD=0.99) donated eight saliva samples (later assayed for cortisol) over the course of a 3-h laboratory session. Supportive behaviors were coded during a conflict and jealousy interaction task from video recordings, and participants completed pre-and-post task questionnaires. Parallel process latent growth models revealed a strong positive association between the couples' cortisol intercept, indicating that couples show attunement in initial levels of cortisol. Further, observed supportive behavior moderated the strength of the association between dyadic cortisol slopes. The results imply that low levels of supportive behavior predicted stronger adrenocortical attunement in the change in cortisol levels over time between adolescent romantic partners. These findings indicate that even early romantic relationships exhibit coordination of physiological activity. Findings raise the possibility that adrenocortical attunement may be a dyadic pathway through which the proximal social context of early romantic relationships is translated into risk or resilience in health and behavior.

The Use of Inhaled Nitric Oxide in a Tertiary Neonatal Intensive Care Unit.

There is currently insufficient evidence to create a standardised protocol for the use and weaning of inhaled nitric oxide (iNO). We aimed to determine our application of iNO in this patient cohort. We performed a retrospective chart review on patients receiving iNO therapy for persistent pulmonary hypertension of the newborn (PPHN) from a single tertiary neonatal centre in 2014. The data was entered into the European Inhaled Nitric Oxide Registry. Thirty two babies were treated with iNO during this period, 9 of which were less than 32 weeks gestation. The median time to initiation of iNO treatment was 4-5 hours and the median duration of treatment was 74 hours for term and 66 hours for preterm infants. We recommend that further use of the European Inhaled Nitric Oxide Registry across more neonatal units in the Republic of Ireland could lead to the development of national guidelines on iNO use and weaning in this cohort.

The effect of antenatal magnesium sulfate on left ventricular afterload and myocardial function measured using deformation and rotational mechanics imaging.

OBJECTIVE: Assess the effect of antenatal magnesium sulfate (MgSO4) on left ventricular function measured using deformation and rotational mechanics imaging. STUDY DESIGN: Infants who received MgSO4 were matched for gestation, birth weight and mode of delivery with controls. Echocardiography was carried out on days 1 and 2 to measure left ventricle longitudinal strain (LV LS), twist, untwist rate, ejection fraction (EF), and systemic vascular resistance (SVR). RESULTS: Thirty-eight infants with a median gestation and birth weight of 27.1 weeks and 923 g were included. On day 1, the MgSO4 group (n=19) had a lower SVR and higher LV LS, EF, twist and untwist rate than the Control group (n=19) (all P<0.05). There were no differences between the groups on day 2. CONCLUSION: Antenatal MgSO4 administration is associated with a lower SVR and higher myocardial function on day 1 in preterm infants <29 weeks gestation.

Treatment of premature infants with pulmonary hypertension and right ventricular dysfunction with milrinone: a case series.

OBJECTIVE: Milrinone has been proposed as an effective treatment for pulmonary hypertension (PH) and right ventricular (RV) dysfunction. We aimed to determine the effect of milrinone therapy on clinical and echocardiography parameters of PH in preterm infants with elevated pulmonary pressures. STUDY DESIGN: A retrospective case review was conducted on infants <32 weeks gestation who received milrinone for the treatment of PH and reduced RV function. Echocardiographic data were collected before and after treatment with milrinone, and serial clinical parameters were recorded over a 72h period. RESULT: Seven infants met the inclusion criteria with a median gestation and birth weight of 27.3 weeks and 1140 g, respectively. Four infants had a diagnosis of pulmonary hypoplasia with PH, and three infants were recipients in twin-to-twin transfusion syndrome who also developed PH. Nitric oxide was used in six infants before commencement of milrinone. Milrinone was commenced at a dose of 0.33 µg kg(-1) min(-1) to 0.5 µg kg(-1) min(-1) and continued for a median duration of 70 h. Use of milrinone was associated with a fall in oxygenation index and inhaled nitric oxide dose. Following an initial fall in blood pressure over the first 6 h, there was an increase in blood pressure over the subsequent 72 h. Echocardiographic data demonstrated an increase in indicators of myocardial performance and PH. One infant died before discharge. CONCLUSION: This case series suggests that milrinone may be a useful therapy for premature infants with echocardiography findings of PH and/or RH dysfunction. This data support the need for a randomised control trial to confirm its efficacy.

Gemtuzumab ozogamicin in children and adolescents with de novo acute myeloid leukemia improves event-free survival by reducing relapse risk: results from the randomized phase III Children's Oncology Group trial AAML0531.

PURPOSE: To improve survival rates in children with acute myeloid leukemia (AML), we evaluated gemtuzumab-ozogamicin (GO), a humanized immunoconjugate targeted against CD33, as an alternative to further chemotherapy dose escalation. Our primary objective was to determine whether adding GO to standard chemotherapy improved event-free survival (EFS) and overall survival (OS) in children with newly diagnosed AML. Our secondary objectives examined outcomes by risk group and method of intensification. PATIENTS AND METHODS: Children, adolescents, and young adults ages 0 to 29 years with newly diagnosed AML were enrolled onto Children's Oncology Group trial AAML0531 and then were randomly assigned to either standard five-course chemotherapy alone or to the same chemotherapy with two doses of GO (3 mg/m2/dose) administered once in induction course 1 and once in intensification course 2 (two of three). RESULTS: There were 1,022 evaluable patients enrolled. GO significantly improved EFS (3 years: 53.1% v. 46.9%; hazard ratio [HzR], 0.83; 95% CI, 0.70 to 0.99; P.04) but not OS (3 years: 69.4% v. 65.4%; HzR, 0.91; 95% CI, 0.74 to 1.13; P = .39). Although remission was not improved (88% v. 85%; P = .15), posthoc analyses found relapse risk (RR) was significantly reduced among GO recipients overall (3 years: 32.8% v. 41.3%; HzR, 0.73; 95% CI, 0.58 to 0.91; P = .006). Despite an increased postremission toxic mortality (3 years: 6.6% v. 4.1%; HzR, 1.69; 95% CI, 0.93 to 3.08; P = .09), disease-free survival was better among GO recipients (3 years: 60.6% v. 54.7%; HzR, 0.82; 95% CI, 0.67 to 1.02; P = .07). CONCLUSION: GO added to chemotherapy improved EFS through a reduction in RR for children and adolescents with AML.

A Phase 2 study of bortezomib combined with either idarubicin/cytarabine or cytarabine/etoposide in children with relapsed, refractory or secondary acute myeloid leukemia: a report from the Children's Oncology Group.

BACKGROUND: This Phase 2 study tested the tolerability and efficacy of bortezomib combined with reinduction chemotherapy for pediatric patients with relapsed, refractory or secondary acute myeloid leukemia (AML). Correlative studies measured putative AML leukemia initiating cells (AML-LIC) before and after treatment. PROCEDURE: Patients with <400 mg/m(2) prior anthracycline received bortezomib combined with idarubicin (12 mg/m(2) days 1-3) and low-dose cytarabine (100 mg/m(2) days 1-7) (Arm A). Patients with ≥400 mg/m(2) prior anthracycline received bortezomib with etoposide (100 mg/m(2) on days 1-5) and high-dose cytarabine (1 g/m(2) every 12 hours for 10 doses) (Arm B). RESULTS: Forty-six patients were treated with 58 bortezomib-containing cycles. The dose finding phase of Arm B established the recommended Phase 2 dose of bortezomib at 1.3 mg/m(2) on days 1, 4, and 8 with Arm B chemotherapy. Both arms were closed after failure to meet predetermined efficacy thresholds during the first stage of the two-stage design. The complete response (CR + CRp) rates were 29% for Arm A and 43% for Arm B. Counting additional CRi responses (CR with incomplete neutrophil recovery), the overall CR rates were 57% for Arm A and 48% for Arm B. The 2-year overall survival (OS) was 39 ± 15%. Correlative studies showed that LIC depletion after the first cycle was associated with clinical response. CONCLUSION: Bortezomib is tolerable when added to chemotherapy regimens for relapsed pediatric AML, but the regimens did not exceed preset minimum response criteria to allow continued accrual. This study also suggests that AML-LIC depletion has prognostic value.

Mode of delivery in pregnancies complicated by major fetal congenital heart disease: a retrospective cohort study.

OBJECTIVE: To determine the mode of delivery in pregnancies complicated by complex fetal congenital heart disease (CHD). STUDY DESIGN: Five-year retrospective cohort study at a tertiary fetal medicine center (2007 to 2011). Cases of complex fetal CHD (n=126) were compared with 45 069 non-anomalous singleton infants ⩾500 g to determine rates of emergency intrapartum cesarean section (CS), preterm delivery and induction of labor. RESULT: Intrapartum CS is significantly higher in fetal CHD than non-anomalous controls (21% vs 13.5%, odds ratio (OR) 1.7, 95% confidence interval (CI): 1.0 to 2.7; P=0.035), predominantly related to CS for non-reassuring fetal status (OR 2.2, 95% CI: 1.1 to 4.1; P=0.022). Although fetal CHD did not increase emergency CS rates in nulliparous women, CS was significantly increased in multiparous pregnancies (OR 2.4, 95% CI: 1.8 to 4.6; P=0.014). Rates of preterm delivery (OR 3.4, 95% CI: 2.0 to 5.4; P<0.0001) and induction of labor (OR 1.9, 95% CI: 1.3 to 2.9; P=0.001) were higher in the CHD cases. CONCLUSION: Emergency CS is increased in fetal CHD, attributed to a higher rate of CS for non-reassuring fetal status and seen mostly in multiparous women.

Outcome of transplantation for acute lymphoblastic leukemia in children with Down syndrome.

We report on 27 patients with Down syndrome (DS) and acute lymphoblastic leukemia (ALL) who received allogeneic hematopoietic cell transplantation (HCT) between 2000 and 2009. Seventy-eight percent of patients received myeloablative conditioning and 52% underwent transplantation in second remission. Disease-free survival (DFS) was 24% at a median of 3 years. Post-transplant leukemic relapse was more frequent than expected for children with DS-ALL (54%) than for non-DS ALL. These data suggest leukemic relapse rather than transplant toxicity is the most important cause of treatment failure. Advancements in leukemia control are especially needed for improvement in HCT outcomes for DS-ALL.

Oxandrolone for the treatment of bone marrow failure in Fanconi anemia.

BACKGROUND: A majority of Fanconi anemia (FA) patients will experience bone marrow failure (BMF) and androgen therapy (most often oxymetholone) may be utilized as a treatment to improve BMF-related cytopenias. However, oxymetholone is associated with toxicities making identification of other agents of interest. In this study we aimed to evaluate the toxicity profile and hematologic response in patients with FA who are treated with low-dose oxandrolone, a synthetic non-fluorinated anabolic steroid, similar to oxymetholone, with known dosing thresholds for virilization. PROCEDURE: A single arm, Phase I/II study was designed to treat patients on low-dose oxandrolone. If no toxicity or hematologic response was noted at 16 weeks, a single dose escalation was offered. Subjects were regularly assessed for toxicity, including determinations of virilization, behavioral changes, and liver and kidney function. At 32 weeks, those who demonstrated hematologic response were allowed to continue study treatment, and those without improvement were deemed non-responsive. RESULTS: Nine subjects completed the study and were followed for a median of 99 weeks (46-136 weeks). Three (33.3%) subjects developed mild sub-clinical virilization and continued treatment with a dose reduction. None (0%) had adverse behavioral changes. Two (22.2%) developed elevated liver function tests at 42 and 105 weeks. Seven (77.8%) subjects had a hematologic response. CONCLUSION: Oxandrolone appears to be well-tolerated, has limited toxicities at the administered doses in FA with patients, and may be an alternative androgen for the treatment of BMF in FA.