Sleep and asthma management in youth with poorly-controlled asthma and their caregivers: a qualitative approach.

OBJECTIVE: Youth with poorly-controlled asthma are at increased risk for sleep disturbances caused by nocturnal symptoms like coughing. Asthma-related sleep disturbances can have downstream consequences for youth with asthma and their families. This study aims to describe (1) sleep disturbances in adolescents with poorly-controlled asthma and their caregivers and (2) the relationship between sleep and asthma management. METHODS: Adolescents with poorly-controlled asthma and their caregivers completed the Family Asthma Management System Scale (FAMSS), a semi-structured interview that assesses youth asthma management within the family context. Interviews were audio-recorded and transcribed. Two authors coded each transcript for sleep-related data in NVivo using descriptive content analysis. RESULTS: Thirty-three adolescents ages 12-15 years old (M = 13.2, SD = 1.2) with poorly-controlled asthma and their caregivers participated in this study. Four main themes emerged: sleep difficulties, sleep environment, sleep and self-management, and fatigue and self-management. 42% of youth and caregivers reported worse nocturnal asthma symptoms (e.g. coughing) that caused frequent nighttime awakening. Approximately 27% of caregivers expressed distress over their child's nocturnal asthma and described their management strategies (e.g. co-sleeping, nighttime symptom monitoring). Adolescents described sleepiness as a barrier to asthma self-management tasks (e.g. medication adherence, response to exacerbation). CONCLUSION: Interview responses demonstrated the considerable interrelationship of sleep and asthma management in adolescents with poorly-controlled asthma. Asthma providers should consider discussing sleep difficulties with their adolescent patients and their families. Addressing these difficulties may help adolescents improve their asthma self-management and help caregivers better cope with their child's disease.

Legal Needs, Health, and Health Care Utilization Among Patients Participating in the Delaware Medical Legal Partnership.

CONTEXT: Unmet legal needs can exacerbate health disparities and contribute to a lack of adherence to treatment plans and medical recommendations for care. Medical legal partnerships (MLPs) are integrated health care and legal aid interventions offered by many health systems in the United States. Although much research has been published regarding the success of MLPs with specific patient groups, there is a gap in literature regarding the nature of MLPs in a more general, at-risk patient population. OBJECTIVE: We aimed to better understand specific patient characteristics and health outcomes associated with different iHELP legal needs. DESIGN: This is a cross-sectional study of patients who were enrolled in the Delaware MLP (DMLP) from November 2018 to June 2020 (N = 212). SETTING: The DMLP is a collaboration between ChristianaCare, a Mid-Atlantic health system, and the Community Legal Aid Society, Inc (CLASI). PARTICIPANTS: Patients must be adults (ie, 18 years or older), below 200% of the federal poverty level (eg, ≤$53 000 for a household of 4 as of 2021), have at least one qualifying legal need, and live in the state. INTERVENTION: The DMLP is designed to address unmet legal needs that fall under a framework called iHELP. iHELP legal domains are income and insurance (i), housing and utilities (H), education and employment (E), legal status (L), and personal and family stability (P). MAIN OUTCOME MEASURES: Outcomes of interest were iHELP legal needs, patient demographics, perceived stress and mental and physical health-related quality of life, comorbidities, and health care utilization. RESULTS: Housing and utilities (46.2%) and income support (41.5%) were the highest reported legal needs. Perceived stress scores were significantly higher for those with income needs (P = .01) as well as those with housing and utilities needs (P = .01). CONCLUSIONS: MLP programs offer a value-added service that can address unmet legal needs in vulnerable, at-risk patients.

Asthma Management Responsibility, Control, and Quality of Life Among Emerging Adolescents.

OBJECTIVE: To examine how asthma control is related to the association between the division of responsibility for asthma management and asthma-related quality of life among early adolescents. METHODS: Forty-nine youth aged 10-15 years (Mage = 12.25, 57.1% female) with a physician-verified asthma diagnosis completed the Standardized Pediatric Asthma Quality of Life Questionnaire (PAQLQ) and Asthma Control Test (ACT). Youth and their caregivers also completed the Asthma Responsibility Questionnaire (ARQ). Higher ACT scores indicate better asthma control. RESULTS: There was a significant difference in ARQ scores between youth and caregivers (p < .001, d = .94). Youth reported sharing equal responsibility for asthma management with caregivers, while caregivers reported having more responsibility relative to youth. Greater youth-reported ARQ (p = .004) and greater ACT scores (p < .001) were associated with higher PAQLQ scores. ACT scores moderated the effect of youth-reported ARQ on PAQLQ scores (p = .043). For youth with lower ACT scores, higher youth-reported responsibility was associated with higher PAQLQ scores; while for youth with higher ACT scores, PAQLQ scores were high regardless of perceived responsibility. The interaction between caregiver ARQ scores and ACT scores was not significant. CONCLUSION: This study suggests youth and caregivers report discrepant ARQ for asthma management tasks. Responsibility and level of asthma control are important factors for PAQLQ, with results indicating that fostering responsibility is an important factor, even among youth with poorly controlled asthma. Findings suggest that healthcare providers should assess family responsibility and help caregivers support adolescents in developing asthma management skills.

Determining Adherence to Inhaled Corticosteroids From the Epic Electronic Medical Record.

OBJECTIVE: Often we call the patient's pharmacy to obtain a refill history to assess inhaled corticosteroid (ICS) adherence. The purpose of this project was to determine the accuracy of refill histories for ICS (with or without long-acting beta agonist) listed in Epic's Medication Dispense History. METHODS: We evaluated 61 patients and used data from 38 who met the following criteria: 1) under the care of the UF Pediatric Severe Asthma Clinic; 2) taking the same dose of the same ICS product for 6 months before the patient's last clinic visit; and 3) having data available from the pharmacy where the last ICS prescription was electronically sent. We called the pharmacies to obtain a verbal report of their refill record. Then, we compared the number of refills reported to the number listed in Epic's records using a Wilcoxon matched-pairs signed-ranks test. RESULTS: Of the 293 refill dates listed in Epic, 157 were duplicates, giving a 54% error. After deleting duplicates, the mean (SD) number of refills listed in Epic was 3.6 (2.0) compared with 3.3 (2.0) in pharmacies over a period of 6 months (p < 0.0001). After removing duplicates Epic correctly reported the total number of refills for 30 of the 38 patients (78.9%). Seven of the remaining patients had more refills listed in Epic while 1 patient had more refills dispensed. CONCLUSION: This study indicates that our version of Epic over-reports refills thus limiting assessment of adherence. In contrast, absence of refills in Epic is a clear indication of poor adherence.

Evolution of pancreatic function during the first year in infants with cystic fibrosis.

OBJECTIVE: To describe pancreatic function during the first year of life in infants diagnosed with cystic fibrosis (CF) using serial fecal elastase measurements. STUDY DESIGN: This was a longitudinal study of 82 infants diagnosed with CF through newborn screening. Monthly stool samples were sent to a central laboratory for fecal elastase measurements. RESULTS: A total of 61 infants had an initial stool sample obtained at age <3.5 months and a final stool sample obtained at age >9 months. Twenty-six of 29 infants with a fecal elastase value <50 µg/g at study entry had a fecal elastase value <200 µg/g (the accepted cutoff value for pancreatic insufficiency) on all measurements during the year; all 29 had a value <200 µg/g at the end of the study. Of the 48 infants with initial fecal elastase value <200 µg/g, 13 had at least 1 fecal elastase value >200 µg/g but had a final stool fecal elastase value <200 µg/g; however, 4 infants with an initial fecal elastase value <200 µg/g ended the year with a value >200 µg/g. Eleven of 13 infants with an initial fecal elastase value of >200 µg/g still had a value >200 µg/g at the end of the first year. CONCLUSION: Infants with CF exhibit variability in fecal elastase values during the first year. Infants with a fecal elastase level of 50-200 µg/g at diagnosis should be treated with pancreatic enzyme replacement therapy, but fecal elastase should be remeasured at age 1 year to ensure that those with a falsely low value do not continue to receive pancreatic enzyme replacement therapy unnecessarily. Those with a fecal elastase value >200 µg/g initially can become pancreatic insufficient with time.

Using hyperpolarized 3He MRI to evaluate treatment efficacy in cystic fibrosis patients.

PURPOSE: To use hyperpolarized (HP) (3)He MR imaging to assess functional lung ventilation in subjects with cystic fibrosis (CF) before and after treatment. MATERIALS AND METHODS: We performed HP (3)He static ventilation MRI scans on three subjects, using a Philips 3.0 Tesla (T) Achieva MRI scanner, before and after 11 days of in-patient treatment with combined intravenous and inhaled therapies for pulmonary exacerbations of CF. We also collected spirometry data. We quantified pulmonary ventilation volume measured with HP (3)He MRI using an advanced semi-automated analysis technique. RESULTS: Following 11 days of treatment with intravenous antibiotics, hypertonic saline, and rhDNase, HP (3)He MR images in one subject displayed a 25% increase in total ventilation volume. Total ventilation volume in the other two subjects slightly decreased. All three subjects showed increases in FEV(1) and FVC following treatment. CONCLUSION: In all subjects, the HP (3)He MR images provided detailed information on precisely where in the lungs gas was reaching. These data provide additional support for the conclusion that HP noble gas MRI can be a powerful tool for evaluating lung ventilation in patients with cystic fibrosis, but also raise important questions about the correlation between spirometry and HP gas MRI measurements.

Continuous Albuterol With Benzalkonium in Children Hospitalized With Severe Asthma.

BACKGROUND AND OBJECTIVES: The albuterol dropper bottle used to prepare solutions for continuous nebulization contains the preservative benzalkonium chloride (BAC). BAC, by itself, has been shown to cause bronchospasm. We hypothesized that BAC would decrease the therapeutic efficacy of albuterol in patients with acute asthma exacerbations. METHODS: We performed a retrospective cohort study comparing the clinical outcomes of patients <18 years of age receiving continuous nebulized albuterol with and without BAC. For the primary end point (duration of continuous albuterol nebulization), we compared the 2 groups with Kaplan-Meier estimate of survival curves, conducted a log-rank test of difference, and adjusted for baseline characteristics using multivariable Cox regression. A P value <.05 was considered significant. RESULTS: A total of 477 patients were included in the analysis (236 exposed to BAC and 241 controls). The duration of continuous nebulization was significantly longer in the BAC group than in the control group (median of 9 vs 6 hours; 15.7% required continuous nebulization compared to 5.8% of controls at 24 hours). The control group was 79% more likely to stop continuous nebulization at any particular point in time (hazard ratio 1.79; 95% confidence interval: 1.45 to 2.22; P < .001) and 43% more likely to stop additional respiratory support (hazard ratio 1.43; 95% confidence interval: 1.16 to 1.75; P < .001). CONCLUSIONS: BAC is a functional albuterol antagonist associated with a longer duration of continuous albuterol nebulization treatment and additional respiratory support, suggesting that preservative-free albuterol formulations are safer for use in continuous nebulization.

Upper versus lower airway microbiome and metagenome in children with cystic fibrosis and their correlation with lung inflammation.

OBJECTIVE: Airways of children with cystic fibrosis (CF) harbor complex polymicrobial communities which correlates with pulmonary disease progression and use of antibiotics. Throat swabs are widely used in young CF children as a surrogate to detect potentially pathogenic microorganisms in lower airways. However, the relationship between upper and lower airway microbial communities remains poorly understood. This study aims to determine (1) to what extent oropharyngeal microbiome resembles the lung microbiome in CF children and (2) if lung microbiome composition correlates with airway inflammation. METHOD: Throat swabs and bronchoalveolar lavage (BAL) were obtained concurrently from 21 CF children and 26 disease controls. Oropharyngeal and lung microbiota were analyzed using 16S rRNA deep sequencing and correlated with neutrophil counts in BAL and antibiotic exposure. RESULTS: Oropharyngeal microbial communities clustered separately from lung communities and had higher microbial diversity (p < 0.001). CF microbiome differed significantly from non-CF controls, with a higher abundance of Proteobacteria in both upper and lower CF airways. Neutrophil count in the BAL correlated negatively with the diversity but not richness of the lung microbiome. In CF children, microbial genes involved in bacterial motility proteins, two-component system, flagella assembly, and secretion system were enriched in both oropharyngeal and lung microbiome, whereas genes associated with synthesis and metabolism of nucleic acids and protein dominated the non-CF controls. CONCLUSIONS: This study identified a unique microbial profile with altered microbial diversity and metabolic functions in CF airways which is significantly affected by airway inflammation. These results highlight the limitations of using throat swabs as a surrogate to study lower airway microbiome and metagenome in CF children.

Direct Observed Therapy of Inhaled Corticosteroids for Asthma at School or Daycare.

Background: Poor adherence with inhaled corticosteroid (ICS) medication is common in the pediatric population and can result in poor asthma control with increased frequency of asthma-related complications. The purpose of this study was to determine whether or not the initiation of ICS administration twice per day at school/daycare in patients with poor medication adherence at home improves asthma health care outcomes. Methods: We retrospectively selected patients followed by our Pediatric Pulmonology Clinic who had poorly controlled asthma and had been assigned to receive ICS twice daily at school/daycare due to poor adherence with ICS therapy. We analyzed the number of short courses of oral corticosteroids, hospital admissions, emergency department visits, and intramuscular methylprednisolone administrations for asthma exacerbations for the year before and after the intervention. The Wilcoxon signed rank test with continuity correction was used in the primary analysis. Results: Forty-nine patients who met the inclusion criteria were identified, but only 40 actually started the intervention. The number of oral corticosteroid courses per year decreased from 1.35 ± 1.1 before the intervention to 0.68 ± 1.2 (P = 0.008) postintervention, hospital admissions per year decreased from 0.45 ± 0.7 to 0.10 ± 0.3 (P = 0.006), emergency department visits per year decreased from 0.55 ± 0.8 to 0.28 ± 0.6 (P = 0.084), and intramuscular repository methylprednisolone injections per year for asthma exacerbations decreased from 0.20 ± 0.4 to 0.10 ± 0.3 (P = 0.23). Conclusion: These results indicate that school/daycare administration of ICS may be an effective option to improve indicators of asthma exacerbations in children with poor adherence to ICS at home.

A Behavioral Family Intervention for Children with Overweight and Asthma.

OBJECTIVE: The Childhood Health and Asthma Management Program (CHAMP) is a behavioral family lifestyle intervention for youth with overweight or obesity (OV/OB) and asthma. This pilot randomized controlled trial examined the feasibility, acceptability, and preliminary efficacy of CHAMP. METHODS: A sample of 24 children (Mage = 8.67) with asthma and a BMI ≥ 85th percentile and their caregivers participated in a pilot randomized controlled trial. Families were recruited from local pediatrician offices and pediatric pulmonary and allergy clinics and randomized to CHAMP or a health education attention control condition. Children's height, weight, lung function, asthma control, and asthma-related quality of life (QOL) were collected at baseline, post-intervention, and 6-months post-treatment. Analysis of covariance and standardized mean differences were used to assess changes in outcome variables among participants attending > 50% of sessions (n = 12). RESULTS: Families participating in CHAMP reported high satisfaction; however, there were a number of barriers to recruitment and regular session attendance. There were no statistically significant between group differences at post-intervention or long-term follow-up. From baseline to post-intervention, there were small to large effect sizes favoring CHAMP for BMI z-scores, asthma control, and measures of lung function. There were small to medium effect sizes favoring CHAMP at long-term follow-up for BMI z-scores, asthma control, and asthma-related QOL. CONCLUSIONS: CHAMP had adequate acceptability in this trial. We did not find significant results favoring CHAMP in comparison to the control group, however, lessons learned provide important directions for modifications in anticipation of a larger trial.

Emotional memory and perception of emotional faces in patients suffering from depersonalization disorder.

Previous work has shown that patients with depersonalization disorder (DPD) have reduced physiological responses to emotional stimuli, which may be related to subjective emotional numbing. This study investigated two aspects of affective processing in 13 patients with DPD according to the DSM-IV criteria and healthy controls: the perception of emotional facial expressions (anger, disgust, fear, happiness, sadness, and surprise) and memory for emotional stimuli. Results revealed a specific lack of sensitivity to facial expression of anger in patients, but normal enhancement of memory for peripheral aspects of arousing emotional material. The results are consistent with altered processing of threat-related stimuli but intact consolidation processes, at least when the stimuli involved are potently arousing.

Phase I trial of intramuscular injection of a recombinant adeno-associated virus serotype 2 alphal-antitrypsin (AAT) vector in AAT-deficient adults.

A phase I trial of intramuscular injection of a recombinant adeno-associated virus serotype 2 (rAAV2) alpha1-antitrypsin (AAT) vector was performed in 12 AAT-deficient adults, 10 of whom were male. All subjects were either homozygous for the most common AAT mutation (a missense mutation designated PI*Z) or compound heterozygous for PI*Z and another mutation known to cause disease. There were four dose cohorts, ranging from 2.1 x 10(12) vector genomes (VG) to 6.9 x 10(13) VG, with three subjects per cohort. Subjects were injected sequentially in a dose-escalating fashion with a minimum of 14 days between patients. Subjects who had been receiving AAT protein replacement discontinued that therapy 28 days before vector administration. There were no vector-related serious adverse events in any of the 12 participants. Vector DNA sequences were detected in the blood between 1 and 3 days after injection in nearly all patients receiving doses of 6.9 x 10(12) VG or higher. Anti-AAV2 capsid antibodies were present and rose after vector injection, but no other immune responses were detected. One subject who had not been receiving protein replacement exhibited low-level expression of wild-type M-AAT in the serum (82 nM), which was detectable 30 days after receiving an injection of 2.1 x 10(13) VG. Unfortunately, residual but declining M-AAT levels from the washout of the protein replacement elevated background levels sufficiently to obscure any possible vector expression in that range in most of the other individuals in the higher dose cohorts.

Lamotrigine as an add-on treatment for depersonalization disorder: a retrospective study of 32 cases.

OBJECTIVES: Depersonalization disorder (DPD) is a chronic condition characterized by the persistent subjective experience of unreality and detachment from the self. To date, there is no known treatment. Lamotrigine as sole agent was not found to be effective in a previous small double-blind, randomized crossover trial. However, evidence from open trials suggests that it may be beneficial as an add-on medication with antidepressants. METHODS: We report here an extended series of 32 patients with DPD in whom lamotrigine was prescribed as an augmenting medication. Most of the patients were receiving selective serotonin reuptake inhibitors. RESULTS: Fifty-six percent (n = 18) of patients had a more than or equal to 30% reduction on the Cambridge Depersonalization Scale score at follow-up. Both maximum dose of lamotrigine used and before treatment Cambridge Depersonalization Scale scores showed positive correlations with the percentage of response. CONCLUSIONS: The results of this trial suggest that a significant number of patients with DPD may respond to lamotrigine when combined with antidepressant medication. The results are sufficiently positive to prompt a larger controlled evaluation of lamotrigine as "add-on" treatment in DPD.

Characterization of FGFR1 Locus in sqNSCLC Reveals a Broad and Heterogeneous Amplicon.

FGFR1 amplification occurs in ~20% of sqNSCLC and trials with FGFR inhibitors have selected FGFR1 amplified patients by FISH. Lung cancer cell lines were profiled for sensitivity to AZD4547, a potent, selective inhibitor of FGFRs 1-3. Sensitivity to FGFR inhibition was associated with but not wholly predicted by increased FGFR1 gene copy number. Additional biomarker assays evaluating expression of FGFRs and correlation between amplification and expression in clinical tissues are therefore warranted. We validated nanoString for mRNA expression analysis of 194 genes, including FGFRs, from clinical tumour tissue. In a panel of sqNSCLC tumours 14.4% (13/90) were FGFR1 amplified by FISH. Although mean FGFR1 expression was significantly higher in amplified samples, there was significant overlap in the range of expression levels between the amplified and non-amplified cohorts with several non-amplified samples expressing FGFR1 to levels equivalent to amplified samples. Statistical analysis revealed increased expression of FGFR1 neighboring genes on the 8p12 amplicon (BAG4, LSM1 and WHSC1L1) in FGFR1 amplified tumours, suggesting a broad rather than focal amplicon and raises the potential for codependencies. High resolution aCGH analysis of pre-clinical and clinical samples supported the presence of a broad and heterogeneous amplicon around the FGFR1 locus. In conclusion, the range of FGFR1 expression levels in both FGFR1 amplified and non-amplified NSCLC tissues, together with the breadth and intra-patient heterogeneity of the 8p amplicon highlights the need for gene expression analysis of clinical samples to inform the understanding of determinants of response to FGFR inhibitors. In this respect the nanoString platform provides an attractive option for RNA analysis of FFPE clinical samples.

Identification of Pharmacodynamic Transcript Biomarkers in Response to FGFR Inhibition by AZD4547.

The challenge of developing effective pharmacodynamic biomarkers for preclinical and clinical testing of FGFR signaling inhibition is significant. Assays that rely on the measurement of phospho-protein epitopes can be limited by the availability of effective antibody detection reagents. Transcript profiling enables accurate quantification of many biomarkers and provides a broader representation of pathway modulation. To identify dynamic transcript biomarkers of FGFR signaling inhibition by AZD4547, a potent inhibitor of FGF receptors 1, 2, and 3, a gene expression profiling study was performed in FGFR2-amplified, drug-sensitive tumor cell lines. Consistent with known signaling pathways activated by FGFR, we identified transcript biomarkers downstream of the RAS-MAPK and PI3K/AKT pathways. Using different tumor cell lines in vitro and xenografts in vivo, we confirmed that some of these transcript biomarkers (DUSP6, ETV5, YPEL2) were modulated downstream of oncogenic FGFR1, 2, 3, whereas others showed selective modulation only by FGFR2 signaling (EGR1). These transcripts showed consistent time-dependent modulation, corresponding to the plasma exposure of AZD4547 and inhibition of phosphorylation of the downstream signaling molecules FRS2 or ERK. Combination of FGFR and AKT inhibition in an FGFR2-mutated endometrial cancer xenograft model enhanced modulation of transcript biomarkers from the PI3K/AKT pathway and tumor growth inhibition. These biomarkers were detected on the clinically validated nanoString platform. Taken together, these data identified novel dynamic transcript biomarkers of FGFR inhibition that were validated in a number of in vivo models, and which are more robustly modulated by FGFR inhibition than some conventional downstream signaling protein biomarkers. Mol Cancer Ther; 15(11); 2802-13. ©2016 AACR.

Cognitive-behaviour therapy for depersonalisation disorder: an open study.

Depersonalisation (DP) and derealisation (DR) are subjective experiences of unreality in, respectively, one's sense of self and the outside world. These experiences occur on a continuum from transient episodes that are frequently reported in healthy individuals to a chronic psychiatric disorder that causes considerable distress (depersonalisation disorder: DPD). Despite the relatively high rates of reporting these symptoms, little research has been conducted into psychological treatments for this disorder. We report on an open study where 21 patients with DPD were treated individually with cognitive behavioural therapy (CBT). The therapy involved helping the patients re-interpret their symptoms in a non-threatening way as well as reducing avoidances, safety behaviours and symptom monitoring. Significant improvements in patient-defined measures of DP/DR severity as well as standardised measures of dissociation, depression, anxiety and general functioning were found at post-treatment and six-months follow-up. Moreover, there were significant reductions in clinician ratings on the Present State Examination (Wing, Cooper & Sartorius, 1974), and 29% of participants no longer met criteria for DPD at the end of therapy. These initial results suggest that a CBT approach to DPD may be effective, but further trials with larger sample sizes and more rigorous research methodology are needed to determine the specificity of this approach.

Phase I trial of intramuscular injection of a recombinant adeno-associated virus alpha 1-antitrypsin (rAAV2-CB-hAAT) gene vector to AAT-deficient adults.

A recombinant virus vector constructed from adeno-associated virus (AAV) that has been altered to carry the human alpha1-antitrypsin (hAAT) gene expressed from a hybrid chicken beta-actin promoter with a cytomegalovirus enhancer has been developed. The construct has been shown to initiate the production of hAAT in animal models closely matching the proposed human trial. The proposed clinical trial is an open-label, phase I study administering recombinant adeno-associated virus alpha1-antitrypsin (rAAV2-CB-hAAT) gene vector intramuscularly to AAT-deficient human subjects where gene expression can be measured directly in blood samples to assess safety. Safety parameters will be measurement of changes in serum chemistries and hematology, urinalysis, pulmonary function testing, semen assay for vector genomes, immunologic response to AAT, and AAV, as well as reported subject history of any symptoms.

Chronic depersonalization following illicit drug use: a controlled analysis of 40 cases.

AIMS: To examine demographic and clinical features of a group of patients reporting chronic depersonalization (DP) following illicit drug use, and to assess whether depersonalization arising in these circumstances constitutes a distinct clinical syndrome. DESIGN: Case-control comparison using self-reports, standardized questionnaires and clinical assessments in a specialized clinic. SETTING: A tertiary referral depersonalization clinic and research unit affiliated to a psychiatric hospital and research centre. PARTICIPANTS: A total of 164 individuals with chronic DP symptoms who had been in contact with the clinic. Forty of these individuals related the onset of symptoms to an episode of illicit drug use. MEASUREMENTS: A wide range of demographic and clinical variables measured using questionnaires and standardized rating scales. FINDINGS: The drug-induced DP group were significantly younger and had a preponderance of males compared to the non-drug group. Certain clinical and phenomenological differences were found between these groups, but in general the groups are strikingly similar. This is reinforced by the fact that when the drug-induced group was compared with an age and sex-matched subset of the non-drug group, differences between groups largely disappeared. CONCLUSIONS: Drug-induced DP does not appear to represent a distinct clinical syndrome. The neurocognitive mechanisms of the genesis and maintenance of DP are likely to be similar across clinical groups, regardless of precipitants.

Assessment of repeatability of hyperpolarized gas MR ventilation functional imaging in cystic fibrosis.

RATIONALE AND OBJECTIVES: Hyperpolarized (HP) gas magnetic resonance imaging (MRI) is an advanced imaging technique that provides high-resolution regional information on lung function without using ionizing radiation. Before this modality can be considered for assessing clinical or investigational interventions, baseline repeatability needs to be established. We assessed repeatability of lung function measurement using HP helium-3 MRI (HP (3)He MRI) in a small cohort of patients with cystic fibrosis (CF). MATERIALS AND METHODS: We examined repeatability of HP (3)He MR images of five patients with CF in four scanning sessions over a 4-week period. We acquired images on a Philips 3.0 Tesla Achieva MRI scanner using a quadrature, flexible, wrap-around, (3)He radiofrequency coil with a fast gradient-echo pulse sequence. We determined ventilation volume and ventilation defect volume using an advanced semiautomatic segmentation algorithm and also quantified ventilation heterogeneity. RESULTS: There were no significant differences in total ventilation volume, ventilation defect volume, ventilation defect percentage, or mean ventilation heterogeneity (repeated-measures analysis of variance, P = .2116, P = .2825, P = .2871, and P = .7265, respectively) in the patients across the four scanning sessions. CONCLUSIONS: Our results indicate that total ventilation volume, ventilation defect volume, ventilation defect percentage, and mean ventilation heterogeneity as assessed by HP gas MRI in CF patients with stable health are reproducible over time. This repeatability and the technique's capability to provide noninvasive high-resolution data on regional lung function without ionizing radiation make (3)He MRI a potentially useful outcome measure for CF-related clinical trials.