Alexandra L. Quittner

Spoken Language Development in Children Following Cochlear Implantation

CONTEXT Cochlear implantation is a surgical alternative to traditional amplification (hearing aids) that can facilitate spoken language development in young children with severe to profound sensorineural hearing loss (SNHL). OBJECTIVE To prospectively assess spoken language acquisition following cochlear implantation in young children. DESIGN, SETTING, AND PARTICIPANTS Prospective, longitudinal, and multidimensional assessment of spoken language development over a 3-year period in children who underwent cochlear implantation before 5 years of age (n = 188) from 6 US centers and hearing children of similar ages (n = 97) from 2 preschools recruited between November 2002 and December 2004. Follow-up completed between November 2005 and May 2008. MAIN OUTCOME MEASURES Performance on measures of spoken language comprehension and expression (Reynell Developmental Language Scales). RESULTS Children undergoing cochlear implantation showed greater improvement in spoken language performance (10.4; 95% confidence interval [CI], 9.6-11.2 points per year in comprehension; 8.4; 95% CI, 7.8-9.0 in expression) than would be predicted by their preimplantation baseline scores (5.4; 95% CI, 4.1-6.7, comprehension; 5.8; 95% CI, 4.6-7.0, expression), although mean scores were not restored to age-appropriate levels after 3 years. Younger age at cochlear implantation was associated with significantly steeper rate increases in comprehension (1.1; 95% CI, 0.5-1.7 points per year younger) and expression (1.0; 95% CI, 0.6-1.5 points per year younger). Similarly, each 1-year shorter history of hearing deficit was associated with steeper rate increases in comprehension (0.8; 95% CI, 0.2-1.2 points per year shorter) and expression (0.6; 95% CI, 0.2-1.0 points per year shorter). In multivariable analyses, greater residual hearing prior to cochlear implantation, higher ratings of parent-child interactions, and higher socioeconomic status were associated with greater rates of improvement in comprehension and expression. CONCLUSION The use of cochlear implants in young children was associated with better spoken language learning than would be predicted from their preimplantation scores.

Inhaled Aztreonam Lysine for Chronic Airway Pseudomonas aeruginosa in Cystic Fibrosis

RATIONALE The effectiveness and safety of aztreonam lysine for inhalation (AZLI) in patients with cystic fibrosis (CF) on maintenance treatment for Pseudomonas aeruginosa (PA) airway infection was evaluated in this randomized, double-blind, placebo-controlled study. OBJECTIVES To evaluate the safety and efficacy of inhaled aztreonam lysine in controlling PA infection in patients with CF. METHODS After randomization and a 28-day course of tobramycin inhalation solution (TIS), patients (n = 211; > or =6 yr; > or =3 TIS courses within previous year; FEV(1) > or = 25% and < or =75% predicted values) were treated with 75 mg AZLI or placebo, twice or three times daily for 28 days, then monitored for 56 days. The primary efficacy endpoint was time to need for additional inhaled or intravenous antipseudomonal antibiotics. Secondary endpoints included changes in respiratory symptoms (CF Questionnaire-Revised [CFQ-R] Respiratory Scale), pulmonary function (FEV(1)), and sputum PA density. Adverse events and minimum inhibitory concentrations of aztreonam for PA were monitored. MEASUREMENTS AND MAIN RESULTS AZLI treatment increased median time to need for additional antipseudomonal antibiotics for symptoms of pulmonary exacerbation by 21 days, compared with placebo (AZLI, 92 d; placebo, 71 d; P = 0.007). AZLI improved mean CFQ-R respiratory scores (5.01 points, P = 0.02), FEV(1) (6.3%, P = 0.001), and sputum PA density (-0.66 log(10) cfu/g, P = 0.006) compared with placebo; no AZLI dose-response was observed. Adverse events reported for AZLI and placebo were comparable and consistent with CF lung disease. Susceptibility of PA to aztreonam at baseline and end of therapy were similar. CONCLUSIONS AZLI was effective in patients with CF using frequent TIS therapy. AZLI delayed time to need for inhaled or intravenous antipseudomonal antibiotics, improved respiratory symptoms and pulmonary function, and was well tolerated. Clinical trial registered with www.clinicaltrials.gov (NCT 00104520).

Role strain in couples with and without a child with a chronic illness: Associations with marital satisfaction, intimacy, and daily mood

This study examined marital role strain in 33 couples caring for a child with cystic fibrosis (CF) and 33 couples with a healthy child. The relationship between role strain, marital satisfaction, and psychological distress was tested. Couples completed a structured interview, questionnaires, a card sort procedure, and 4 daily diaries assessing activities and mood. Couples in the CF versus comparison group reported greater role strain on measures of role conflict, child-care tasks, and exchanges of affection. They also spent less time in recreational activities, but no reliable group differences were found in marital satisfaction or depression. Regression analyses indicated that role strain was related to marital satisfaction and depression and that recreation time accounted for additional variance. Path analysis suggested that recreation mediated the negative relationship between role strain and distress. The importance of using a contextual, process-oriented approach is discussed.

An 18-Month Study of the Safety and Efficacy of Repeated Courses of Inhaled Aztreonam Lysine in Cystic Fibrosis

Chronic airway infection with Pseudomonas aeruginosa (PA) causes morbidity and mortality in patients with cystic fibrosis (CF). Additional anti‐PA therapies are needed to improve health status and health‐related quality of life. AIR‐CF3 was an international 18‐month, open‐label study to evaluate the safety and efficacy of repeated courses of aztreonam for inhalation solution (AZLI, now marketed as Cayston®) in patients aged ≥6 years with CF and PA infection who previously participated in one of two Phase 3 studies: AIR‐CF1 or AIR‐CF2. Patients received up to nine courses (28 days on/28 days off) of 75 mg AZLI two (BID) or three times daily (TID) based on randomization in the previous trials. 274 patients, mean age 28.5 years (range: 8–74 years), participated. Mean treatment adherence was high (92.0% BID group, 88.0% TID group). Hospitalization rates were low and adverse events were consistent with CF. With each course of AZLI, FEV1 and scores on the Cystic Fibrosis Questionnaire‐Revised Respiratory Symptom scale improved and bacterial density in sputum was reduced. Benefits waned in the 28 days off therapy, but weight gain was sustained over the 18 months. There were no sustained decreases in PA susceptibility. A dose response was observed; AZLI TID‐treated patients demonstrated greater improvements in lung function and respiratory symptoms over 18 months. Repeated intermittent 28‐day courses of AZLI treatment were well tolerated. Clinical benefits in pulmonary function, health‐related quality of life, and weight were observed with each course of therapy. AZLI is a safe and effective new therapy in patients with CF and PA airway infection. Pediatr Pulmonol. 2010;45:1121–1134.

Behavioral inhibition, self-regulation of motivation, and working memory in children with attention deficit hyperactivity disorder.

We examined 3 aspects of Barkleys (1997) recent model of Attention Deficit Hyperactivity Disorder (ADHD)-behavioral inhibition, self-regulation of motivation, and working memory utilizing 152 elementary school children ages 7 to 12. Seventy-six children with ADHD and 76 children without a psychiatric diagnosis completed the stop-signal task, a computerized Digit Span Task requiring concurrent storage and processing, and the Kaufman Brief Intelligence Test during a 1-hr testing session. Parent and teacher ratings were also obtained on the Conners Parent Rating Scale-Revised: Long Version (Conners, 1997), and the Conners Teacher Rating Scale-Revised: Long Version (Conners, 1997), respectively. Results indicated that children with ADHD had deficits in inhibitory control, working memory, and short-term memory relative to children without the disorder. Contrary to our prediction, the groups did not differ in their responsiveness to external reinforcement. In addition, children with and without ADHD had similar self-perceptions of their performances during the experimental session. Future directions for specifying childhood difficulties in inhibitory control and memory processes are discussed.

Phase II studies of nebulised Arikace in CF patients with Pseudomonas aeruginosa infection

Rationale Arikace is a liposomal amikacin preparation for aerosol delivery with potent Pseudomonas aeruginosa killing and prolonged lung deposition. Objectives To examine the safety and efficacy of 28 days of once-daily Arikace in cystic fibrosis (CF) patients chronically infected with P aeruginosa. Methods 105 subjects were evaluated in double-blind, placebo-controlled studies. Subjects were randomised to once-daily Arikace (70, 140, 280 and 560 mg; n=7, 5, 21 and 36 subjects) or placebo (n=36) for 28 days. Primary outcomes included safety and tolerability. Secondary outcomes included lung function (forced expiratory volume at one second (FEV1)), P aeruginosa density in sputum, and the Cystic Fibrosis Quality of Life Questionnaire—Revised (CFQ-R). Results The adverse event profile was similar among Arikace and placebo subjects. The relative change in FEV1 was higher in the 560 mg dose group at day 28 (p=0.033) and at day 56 (28 days post-treatment, 0.093L±0.203 vs −0.032L±0.119; p=0.003) versus placebo. Sputum P aeruginosa density decreased >1 log in the 560 mg group versus placebo (days 14, 28 and 35; p=0.021). The Respiratory Domain of the CFQ-R increased by the Minimal Clinically Important Difference (MCID) in 67% of Arikace subjects (560 mg) versus 36% of placebo (p=0.006), and correlated with FEV1 improvements at days 14, 28 and 42 (p<0.05). An open-label extension (560 mg Arikace) for 28 days followed by 56 days off over six cycles confirmed durable improvements in lung function and sputum P aeruginosa density (n=49). Conclusions Once-daily Arikace demonstrated acute tolerability, safety, biologic activity and efficacy in patients with CF with P aeruginosa infection.

The Impact of Audition on the Development of Visual Attention

Interactions between audition and vision were investigated in two experiments In the first experiment, school-age hearing children, deaf children with cochlear implants, and deaf children without implants participated in a task in which they were to respond to some visual signals and not others This task did not involve sound at all Deaf children without implants performed much more poorly than hearing children Deaf children with cochlear implants performed considerably better than deaf children without implants The second experiment employed a longitudinal design and showed that the rate of development in visual selective attention was faster for deaf children with cochlear implants than deaf children without implants Moreover, the gains were rapid—occurring within 2 years post-implant surgery The results suggest that a history of experience with sounds matters in the development of visual attention The results are discussed in terms of multimodal developmental processes

Prevalence of depression and anxiety in patients with cystic fibrosis and parent caregivers: results of The International Depression Epidemiological Study across nine countries

Background Individuals with chronic diseases and parent caregivers are at increased risk for symptoms of depression and anxiety. Prevalence of psychological symptoms was evaluated in adolescents and adults with cystic fibrosis (CF) and parent caregivers across nine countries. Methods Patients with CF, ages 12 years and older, and caregivers of children with CF, birth to18 years of age, completed measures of depression and anxiety across 154 CF centres in Europe and the USA. Psychological symptoms were compared across countries using χ2. Logistic regression examined extent of comorbid symptoms, predictors of depression and anxiety, and concordance between parent and adolescent symptomatology. Results Psychological symptoms were reported by 6088 patients with CF and 4102 parents. Elevated symptoms of depression were found in 10% of adolescents, 19% of adults, 37% of mothers and 31% of fathers. Elevations in anxiety were found in 22% of adolescents, 32% of adults, 48% of mothers and 36% of fathers. Overall, elevations were 2–3 times those of community samples. Participants reporting elevated anxiety were more likely to report depression (ORs: adolescents=14.97, adults=13.64, mothers=15.52, fathers=9.20). Significant differences in reports of depression and anxiety were found by patient age and parent respondent. Concordance between 1122 parent–teen dyads indicated that adolescents whose parents reported depression were more likely to be elevated on depression (OR=2.32). Similarly, adolescents whose parents reported anxiety were more likely to score in the elevated range on the anxiety measure (OR=2.22). Conclusions Symptoms of depression and anxiety were elevated in both patients with CF and parents across several European countries and the USA. Annual screening of psychological symptoms is recommended for both patients and parents.

Measuring Adherence to Medical Treatments in Childhood Chronic Illness: Considering Multiple Methods and Sources of Information

Adherence to medical treatment is a significant problem for children and adolescents with chronic conditions, such as asthma, diabetes, and cystic fibrosis. The consequences of nonadherence can be serious, contributing to increased symptoms, unnecessary hospitalizations, and declines in physical functioning. The quality of data obtained from clinical trials can also be affected by poor adherence, leading to erroneous conclusions concerning the efficacy of drug treatments and the dosages that are needed to achieve those effects. Adherence problems in both clinical research and practice also lead to substantially higher health care costs. In order to further our understanding of the barriers that lead to poor adherence and identify strategies that are effective in addressing them, we need to develop reliable and valid measures of adherence behaviors. Using cystic fibrosis as a model of a serious, chronic disease that requires a difficult and time-consuming medical regimen, three different types of adherence measures are considered: self-report questionnaires, daily diary reports, and electronic monitors. The specific advantages and disadvantages of each type of measurement are reviewed, and specific recommendations are made for future research.

Depressive symptoms in children with cystic fibrosis and parents and its effects on adherence to airway clearance

Little is currently known about the co‐morbidity of depression and cystic fibrosis (CF) and there is currently no empirical research on the effects of depressive symptoms on adherence in children and adolescents with CF. The primary aim of this study was to evaluate the extent of depressive symptoms in children and adolescents with CF and their parents, and determine whether depressive symptoms in the child and/or parent was associated with adherence to airway clearance. We also evaluated whether childrens perceptions of relational security with a parent were associated with adherence to airway clearance.