Retention rate of a novel autoinjector e-Device introduced to patients with chronic arthritis treated with certolizumab pegol in clinical practice: an observational implementation study.

OBJECTIVES: The objectives were to explore the clinical retention rate of an e-Device aimed at empowering chronic arthritis patients using certolizumab pegol (CZP) and to analyse beliefs about medication in the Danish population. METHOD: Patients treated with CZP were recruited from the Netherlands, Denmark, and Sweden through rheumatology clinics at initiation of, or switching to, the e-Device. Patients were adults (aged 18-85 years) diagnosed with rheumatoid arthritis, axial spondyloarthritis, or psoriatic arthritis. Patients administered three consecutive self-injections at home. Descriptive statistics regarding baseline characteristics, retention rates, and reasons for withdrawal were assessed, along with the Beliefs about Medicines Questionnaire. RESULTS: In total, 59 patients participated (Netherlands 25, Denmark 15, Sweden 19). Most subjects (71%) were women, with a mean ± sd age of 55 ± 16.2 years and mean disease duration 12 ± 8.8 years. Six patients (10%) started CZP de novo and the remaining patients switched device. The overall retention rate was 42% after 52 weeks, declining to 38% after 104 weeks. A sharp decline, 34%, was seen at week 8. Between weeks 32 and 112, only four patients (6.8%) withdrew from the study. The primary reason for withdrawal was the patient's request. Stratification by country showed significant differences for some outcomes. CONCLUSION: An initial large dropout was evident within the first 8 weeks, with almost no dropouts thereafter. The reasons for withdrawal were primarily patient requests. Thus, the injection experience must be tailored carefully when selecting patients for new autoinjector e-Devices to enhance retention rates and patient satisfaction.

Increased prevalence of sleep disturbance in psoriatic arthritis is associated with inflammatory and non-inflammatory measures.

OBJECTIVES: To examine the prevalence of sleep disturbances, quantified by the Pittsburgh Sleep Quality Index (PSQI), in patients with psoriatic arthritis (PsA), psoriasis (PsO) and healthy controls (HCs), explore associations between PSQI and clinical and patient-reported outcomes, and evaluate the effect of treatment on PSQI. METHOD: Patients were included from the Parker Institute's PsA patient cohort to evaluate the prevalence of sleep disturbances. Univariate and multivariate regression analyses were used to explore associations between sleep disturbance and outcome measures. Treatment effect in PsA patients was assessed with a mixed-effect model for repeated measures. RESULTS: In total, 109 PsA patients, 20 PsO patients, and 20 HCs were included. Sleep disturbances were reported by 66.1% of PsA patients, 45.0% of PsO patients, and 15.0% of HCs. Univariate regression analyses revealed statistically significant associations (p < 0.001) between PSQI and Disease Activity Score (DAS28CRP), tender points, visual analogue scale (VAS) patient global and pain, Psoriatic Arthritis Impact of Disease fatigue, Health Assessment Questionnaire (HAQ), and painDETECT score. Multivariate regression analysis demonstrated VAS patient global, VAS pain, and tender points as being independently associated with PSQI. The mixed-effect model revealed no effect of treatment. CONCLUSION: More PsA patients than PsO patients and HCs reported sleep disturbances. Sleep disturbances were associated with inflammatory and non-inflammatory measures possibly explaining the limited effect of treatment. This demonstrates the need for interdisciplinary approaches to improve the management of sleep disturbance in PsA.Trial registration: ClinicalTrials.gov (NCT02572700).

Maternal mid-pregnancy C-reactive protein and risk of autism spectrum disorders: the early markers for autism study.

Maternal pregnancy levels of the inflammatory marker C-reactive protein (CRP) has been previously associated with autism spectrum disorder (ASD) in the offspring. We conducted a population-based nested case-control study with 500 children with ASD, 235 with developmental delay (DD) and 580 general population (GP) controls to further investigate whether elevated CRP during pregnancy increases the risk of ASD. Maternal CRP concentration was measured in archived serum collected during 15-19 weeks of pregnancy and genome-wide single-nucleotide polymorphism (SNP) data were generated. The levels of CRP were compared between ASD vs GP and DD vs GP. The genetic associations with CRP were assessed via linear regression. Maternal CRP levels in mid-pregnancy were lower in mothers of ASD compared with controls. The maternal CRP levels in the upper third and fourth quartiles were associated with a 45 and 44% decreased risk of ASD, respectively. Two SNPs at the CRP locus showed strong association with CRP levels but they were not associated with ASD. No difference was found between maternal CRP levels of DD and controls. The reasons for the lower levels of CRP in mothers of ASD are not known with certainty but may be related to alterations in the immune response to infectious agents. The biological mechanisms underlying this association remain to be clarified.

Autism-specific maternal autoantibodies recognize critical proteins in developing brain.

Autism spectrum disorders (ASDs) are neurodevelopmental in origin, affecting an estimated 1 in 88 children in the United States. We previously described ASD-specific maternal autoantibodies that recognize fetal brain antigens. Herein, we demonstrate that lactate dehydrogenase A and B (LDH), cypin, stress-induced phosphoprotein 1 (STIP1), collapsin response mediator proteins 1 and 2 (CRMP1, CRMP2) and Y-box-binding protein to comprise the seven primary antigens of maternal autoantibody-related (MAR) autism. Exclusive reactivity to specific antigen combinations was noted in 23% of mothers of ASD children and only 1% of controls. ASD children from mothers with specific reactivity to LDH, STIP1 and CRMP1 and/or cypin (7% vs 0% in controls; P<0.0002; odds ratios of 24.2 (95% confidence interval: 1.45-405)) had elevated stereotypical behaviors compared with ASD children from mothers lacking these antibodies. We describe the first panel of clinically significant biomarkers with over 99% specificity for autism risk thereby advancing our understanding of the etiologic mechanisms and therapeutic possibilities for MAR autism.

Neuropeptides and neurotrophins in neonatal blood of children with autism or mental retardation.

There has been little exploration of major biologic regulators of cerebral development in autism. In archived neonatal blood of children with autistic spectrum disorders (n = 69), mental retardation without autism (n = 60), or cerebral palsy (CP, n = 63) and of control children (n = 54), we used recycling immunoaffinity chromatography to measure the neuropeptides substance P (SP), vasoactive intestinal peptide (VIP), pituitary adenylate cyclase-activating polypeptide (PACAP), calcitonin gene-related peptide (CGRP), and the neurotrophins nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin 3 (NT3), and neurotrophin 4/5 (NT4/5). Neonatal concentrations of VIP, CGRP, BDNF, and NT4/5 were higher (ANOVA, all p values < 0.0001 by Scheffe test for pairwise differences) in children in the autistic spectrum and in those with mental retardation without autism than in control children. In 99% of children with autism and 97% with mental retardation, levels of at least one of these substances exceeded those of all control children. Concentrations were similar in subgroups of the autistic spectrum (core syndrome with or without mental retardation, other autistic spectrum disorders with or without mental retardation) and in the presence or absence of a history of regression. Among children with mental retardation, concentrations did not differ by severity or known cause (n = 11, including 4 with Down syndrome). Concentrations of measured substances were similar in children with CP as compared with control subjects. SP, PACAP, NGF, and NT3 were not different by diagnostic group. No measured analyte distinguished children with autism from children with mental retardation alone. In autism and in a heterogeneous group of disorders of cognitive function, overexpression of certain neuropeptides and neurotrophins was observed in peripheral blood drawn in the first days of life.

Fluorescence correlation spectroscopy with patterned photoexcitation for measuring solution diffusion coefficients of robust fluorophores.

Patterned fluorescence correlation spectroscopy is developed as a new technique for measuring diffusion coefficients of photostable fluorescent probe molecules. In this method, interference between two intersecting, coherent laser beams creates an excitation fringe pattern from which fluorescence emission is monitored. Spontaneous concentration fluctuations of fluorescent molecules within the excitation volume are detected as excess noise on a fluorescence transient; concentration fluctuations are driven primarily by diffusion of these molecules between interference fringes although contributions from photobleaching and diffusion over the entire pattern dimensions can also be observed. Autocorrelation of the fluorescence transient allows analysis of the temporal characteristics of the fluctuations, which were used to determine solution diffusion coefficients; the method was applied to study the diffusion of Rhodamine 6G (R6G) in water/methanol solutions containing added electrolyte and in pure ethanol. The method can be used to characterize the diffusive transport of fluorescently labeled species, which is an important issue in designing small-volume detection experiments.

Total internal reflection fluorescence correlation spectroscopy for counting molecules at solid/liquid interfaces.

Fluorescence correlation spectroscopy, using tota internal reflection excitation (TIRFCS), is developed as a method to allow quantitative determination of molecular populations at solid/liquid interfaces. Population fluctuations of fluorescent molecules at the interface are observed as excess low-frequency noise on a fluorescence signal. Since the noise arises from molecular origins, its magnitude can be evaluated by Poisson statistics to determine the number of molecules in the interface volume. This quantitative information is available without sensitivity calibration or the preparation of standards and without fitting the transients to a kinetic model. Unlike single-molecule counting measurements, TIRFCS can produce these quantitative results even when the number of photoelectrons detected per molecule is small. Surface populations of rhodamine 6G dye molecules were measured at C-18-derivatized, flat silica surfaces in contact with aqueous solutions and compared with predicted values derived from chromatographic retention data. In addition, electrostatic and nonpolar contributions to the free energy of adsorption of the dye to C-18-modified silica surfaces were examined.

Lateral diffusion of molecules partitioned into silica-bound alkyl chains: influence of chain length and bonding density.

Lateral diffusion of a hydrophobic fluorescent molecule partitioned into monomeric alkyl chains bound to a planar silica substrate was measured as a function of chain density and chain length. Measurement of fluorescence recovery after patterned photobleaching was used to observe the diffusional relaxation of a concentration profile of probe molecules over distances of micrometers. The diffusion rate of the probe molecule partitioned into C-18 chains decreased with decreasing chain coverage. As the chain length was reduced from C-18 to C-8 and C-4, the rate of diffusion also decreased. These results, when combined with results from a previous study of the effect of overlaying solvent on diffusion rate (Hansen, R. L.; Harris, J. M. Anal. Chem. 1995, 67, 492-498), are consistent with a domain model for long-range transport of partitioned molecules through the bound ligands. Fluorescence recovery experiments in which diffusion is monitored over a distance of micrometers offer a unique means to probe long-range structure of surface-immobilized alkyl chains.

Lateral diffusion of molecules partitioned into C-18 ligands on silica surfaces.

Lateral diffusion rates of a fluorescent probe molecule partitioned into chromatographic C-18 ligands on a planar silica substrate were measured as a function of overlaying solvent composition. Diffusion coefficients of the probe were measured with a fluorescence recovery after patterned photobleaching experiment. A total internal reflection fluorescence flow cell held the derivatized planar substrate in contact with various aqueous solutions and allowed the fluorescence signal from two interfering, total internally reflected laser beams to be imaged onto a detector. Diffusion coefficients for the partitioned probe were approximately 3 orders of magnitude smaller than diffusion in solution and were found to increase with increasing methanol concentration in the overlaying aqueous solvent mixture. Inability of a solution phase ionic quencher to quench the fluorescence of sorbed rubrene confirmed that the probe is fully partitioned into the C-18 chains.

Visual evoked potentials and visual processing in stimulant drug-exposed infants.

Prenatal exposure to cocaine and amphetamines has been associated with many adverse effects in infants, including neurological abnormalities. Recent evidence shows that the visual system may be useful in infancy to evaluate neurological functioning. Visual evoked potentials (VEPs) and visual recognition memory testing were carried out on eight infants with prenatal drug-exposure and eight controls, matched for ethnicity and socio-economic status. The drug-exposed infants performed significantly worse on the visual recognition test. However, there were no differences between groups on VEP testing and no correlations between tests. The results suggest that the difficulties found in visual recognition memory of drug-exposed infants are not related to neurological maturity, as measured by VEPs.

Research in pregnancy and mental illness: testing old wives' hypotheses.

Methodological challenges encountered in evaluating the relationships between life stress, mental illness and pregnancy outcome are identified and several studies on the relationships between pregnancy and childbirth and psychosocial factors, including life stresses, major psychiatric disorders, and puerperal depression, are reviewed. Certain methodological pitfalls are illustrated by showing how relationships between psychiatric diagnosis, severity of psychiatric symptomatology, life stresses, strains specific to the pregnancy, amount of intervention received and outcome of keeping or losing the infant have been explored. Five stages of research are identified and particular difficulties encountered at each stage are described with application to the authors' longitudinal study.

Perinatal toxicology screening.

Accurate identification of substance abusing mothers and their infants is critical for appropriate medical management as well as the collection of accurate information on the effects of illicit drug use on perinatal morbidity, mortality, and long-term neurobehavioral outcome in the infants. This study examines the differences found using two methods for urine toxicology screening at the time of obstetrical admission to the hospital. The institution of universal screening identified significantly more women than were previously identified through the use of a risk-directed protocol (P less than .0001). Women identified using either protocol were significantly more likely than toxicology-negative women to have had poor prenatal care and to have smoked and used alcohol during pregnancy (P less than .001). In the population studied, the multiple criteria needed to accurately identify mothers with positive-toxicology screens would also include screening over one half of the toxicology-negative mothers.

Visual recognition memory in drug-exposed infants.

Visual recognition memory testing in high-risk infants has been shown to have significant predictive ability for later cognitive deficits. This study evaluated cognition in infants exposed prenatally to illicit stimulant drugs compared with nonexposed controls with a standardized test of visual recognition, the Fagan Test of Infant Intelligence (FTII). Thirty-six healthy, full-term infants with prenatal exposure to cocaine and/or amphetamines and 26 infants with no drug exposures, matched for race and socioeconomic status, were tested. Average FTII scores were significantly lower and the percentage testing at risk significantly higher in the drug-exposed group (p less than .01). Differences between groups were also noted in behaviors dealing with attention, distractibility, and activity level. These data support recent evidence from longitudinal studies showing that infants exposed to drugs prenatally may be at risk for later subtle neurological abnormalities and suggest these difficulties may be identifiable long before the children reach school age.

Neonatal bilirubin exposure and psychoeducational outcome.

The association between neonatal bilirubin exposure and psychoeducational outcome was investigated in a group of grade school children 9 to 11 years old who required neonatal intensive care between 1977 and 1980. Seventy-four children were evaluated with four measures of psychoeducational outcome, including the Kaufman Mental Processing and Achievement Scales, the Beery Visual Motor Integration Test, and the Vineland Adaptive Behavior Scale. A measure of bilirubin binding calculated directly from the albumin concentration correlated significantly with the Kaufman Mental Processing Composite, although other more direct measures of bilirubin exposure (such as maximum serum bilirubin, direct measures of binding, and cumulative bilirubin exposure) did not. Thus, it is possible that the impact on psychoeducational outcome is the result of some other effect of low serum albumin itself, in addition to its ability to bind bilirubin. The correlation of the calculated albumin-determined binding value with the Kaufman Mental Processing Composite suggests that this level, rather than total serum bilirubin, may be more appropriate in determining clinical management.

House dust mites in the West Indies.

The purpose of this study was to determine the role of the house dust mite. Dermatophagoides pteronyssinus (Dp) and Dermatophagoides farinae (Df), in allergic diseases on the island of St. Lucia. Dust samples were taken from living quarters of patients and hospital volunteers. The level of Df antigen in these living quarters was measured by RAST inhibition. All samples showed Df antigen within a large range of values. Prick tests were done to house dust mite and molds on 91 patients with suspected allergic disease with 63 (69%) reacting to at least one antigen. Of these, 56 (88.9%) reacted to one or both mites. House dust mite is a major allergen in St. Lucia.

Diagnosis, treatment, and follow-up of newborns addicted to cocaine.

The Scientific Board of the California Medical Association presents the following inventory of items of progress in pediatrics. Each item, in the judgment of a panel of knowledgeable physicians, has recently become reasonably firmly established, both as to scientific fact and important clinical significance. The items are presented in simple epitome, and an authoritative reference, both to the item itself and to the subject as a whole, is generally given for those who may be unfamiliar with a particular item. The purpose is to assist busy practitioners, students, researchers, or scholars to stay abreast of these items of progress in pediatrics that have recently achieved a substantial degree of authoritative acceptance, whether in their own field of special interest or another. The items of progress listed below were selected by the Advisory Panel to the Section on Pediatrics of the California Medical Association, and the summaries were prepared under its direction.

The perinatal impact of cocaine, amphetamine, and opiate use detected by universal intrapartum screening.

Universal urine testing for cocaine, amphetamines, and opiates was performed on 1643 women admitted to an obstetric service for a 1-year period with 20.5% having positive results. There were 299 patients with positive toxicology results matched for race and discharge date with patients having negative toxicology and drug history. Significant differences in age, prior obstetric history, prenatal care, alcohol history, and smoking were noted between groups. There was a significant decrease in birth weight, head circumference, length, and gestational age for the drug-positive group, which was most marked in cocaine and multiple drug users. These differences persisted after we controlled for smoking, prenatal care, and prior preterm births. Differences in birth weight and head circumference remained after we controlled for gestational age. Rates of congenital anomalies and abruptio placental were similar between groups. Perinatal substance abuse is independently associated with growth retardation and prematurity. Multiple risk factors are frequently present, necessitating a comprehensive approach to prenatal care.

Effect of pregnancy on psychosis: life circumstances and psychiatric symptoms.

As part of an ongoing prospective study to correlate mother and infant outcome with social isolation during pregnancy, the Schedule for Affective Disorders, SADS-C, was administered to twenty-seven psychotic patients late in pregnancy. Extensive standardized evaluation of life stresses and social supports included a Prenatal Interview with sixty items relating to demographics, drug use, health and obstetrical history, family involvement and development expectations of the infant, and a thirty-item Difficult Life Circumstances questionnaire. In this sample the patients' previous life adjustments were stabilized by their pregnancy unless the pregnancy itself created personal stress for the patient. Higher scores on Difficult Life Circumstances were found to be associated with more psychiatric symptomatology. Symptoms of pregnancy confounded SADS-C items measuring vegetative signs of depression. One group of items on the SADS-C appeared to selectively identify a subset of women whose underlying affective symptomatology was potentiated by pregnancy. A second group of items identified women whose symptoms appeared to be reactive to current situational strains.

The effectiveness of visual information processing training with hispanic children.

The purpose of this study was to determine whether one kind of visual information processing training improves performance on visual tasks and on academic achievement. One hundred fifty-three kindergarten, first- and second-grade Hispanic children who were poor visual processors were randomly assigned to either a training, a contrast, or a control group. The training group received tutoring in visual-information processing for approximately seven weeks while the contrast group was given small group instruction with regular curriculum materials. At the conclusion of the training all Ss were administered several visual tasks and achievement measures. Results indicated that only the tutored children performed significantly better than the other children on the Bender Gestalt test and that the attained visual motor integrative skills were maintained over a period of time. However, training in visual processing skills did not increase performance on academic tasks or on a task of basic concepts.