Clinical Sensitivity of Cystic Fibrosis Mutation Panels in a Diverse Population.

Infants are screened for cystic fibrosis (CF) in New York State (NYS) using an IRT-DNA algorithm. The purpose of this study was to validate and assess clinical validity of the US FDA-cleared Illumina MiSeqDx CF 139-Variant Assay (139-VA) in the diverse NYS CF population. The study included 439 infants with CF identified via newborn screening (NBS) from 2002 to 2012. All had been screened using the Abbott Molecular CF Genotyping Assay or the Hologic InPlex CF Molecular Test. All with CF and zero or one mutation were tested using the 139-VA. DNA extracted from dried blood spots was reliably and accurately genotyped using the 139-VA. Sixty-three additional mutations were identified. Clinical sensitivity of three panels ranged from 76.2% (23 mutations recommended for screening by ACMG/ACOG) to 79.7% (current NYS 39-mutation InPlex panel), up to 86.0% for the 139-VA. For all, sensitivity was highest in Whites and lowest in the Black population. Although the sample size was small, there was a nearly 20% increase in sensitivity for the Black CF population using the 139-VA (68.2%) over the ACMG/ACOG and InPlex panels (both 50.0%). Overall, the 139-VA is more sensitive than other commercially available panels, and could be considered for NBS, clinical, or research laboratories conducting CF screening.

Hypnosis in paediatric respiratory medicine.

Hypnotherapy is an often misunderstood yet effective therapy. It has been reported to be useful within the field of paediatric respiratory medicine as both a primary and an adjunctive therapy. This article gives a brief overview of how hypnotherapy is performed followed by a review of its applications in paediatric patients with asthma, cystic fibrosis, dyspnea, habit cough, vocal cord dysfunction, and those requiring non-invasive positive pressure ventilation. As the available literature is comprised mostly of case series, retrospective studies, and only a single small randomized study, the field would be strengthened by additional randomized, controlled trials in order to better establish the effectiveness of hypnosis as a treatment, and to identify the processes leading to hypnosis-induced physiologic changes. As examples of the utility of hypnosis and how it can be taught to children with respiratory disease, the article includes videos that demonstrate its use for patients with cystic fibrosis.

Hypnosis in the treatment of retrograde cricopharyngeus dysfunction: A case report.

Retrograde cricopharyngeus dysfunction (R-CPD) causes an inability to belch. This case report describes the successful treatment of R-CPD with the use of hypnosis. Thereafter, the patient was able to burp small amounts of air, and was encouraged to continue his use of hypnosis as needed. Hypnosis and possibly other noninvasive treatments should be used for R-CPD before employment of more invasive and costly treatments such as botulinum toxin administration.

A Review, Update, and Commentary for the Cough without a Cause: Facts and Factoids of the Habit Cough.

BACKGROUND: A habitual cough, persisting after the cause is gone, was described in a 1694 medical book. Successful treatment of this disorder known as habit cough was reported in 1966 by the "art of suggestion". The purpose of this article is to provide the current basis for diagnosis and treatment of the Habit Cough Syndrome. METHOD: The epidemiology and clinical course of habit cough were reviewed; original data were obtained from three sources. RESULTS: Unique clinical presentation was the basis for diagnosis of habit cough. Diagnosis was made 140 times with increasing frequency over 20 years at the University of Iowa clinic and 55 times over 6 years at a London clinic. Suggestion therapy provided more frequent cessation of cough than just reassurance. A Mayo Clinic archive of chronic involuntary cough found 16 of 60 still coughing 5.9 years after initial evaluation. Ninety-one parents of children with habit cough and 20 adults reported cessation of coughing from viewing a publicly available video of successful suggestion therapy. CONCLUSIONS: Habit cough is recognizable from the clinical presentation. It is effectively treated in most children by suggestion therapy in clinics, by remote video conferencing, and by proxy from viewing a video of effective suggestion therapy.

Age regression in the treatment of needle phobia: a case report.

Trypanophobia (needle phobia) frequently occurs because of negative encounters with medical procedures and/or needles. Trypanophobia ranges in severity from causing mild anxiety, including apprehension about medical procedures, to severe anxiety and complete avoidance of medical care. In this case report, we describe a 29-year-old who underwent hypnosis-facilitated age regression therapy to improve his trypanophobia. Through the guidance of his subconscious, he realized his reaction to needles may not have been directly related to a difficult medical procedure he had undergone at the age of two. The patient's subconscious turned his attention to the anxiety he felt from being separated from his mother at the time of the procedure.

Denufosol tetrasodium in patients with cystic fibrosis and normal to mildly impaired lung function.

RATIONALE: Intervention for cystic fibrosis lung disease early in its course has the potential to delay or prevent progressive changes that lead to irreversible airflow obstruction. Denufosol is a novel ion channel regulator designed to correct the ion transport defect and increase the overall mucociliary clearance in cystic fibrosis lung disease by increasing chloride secretion, inhibiting sodium absorption, and increasing ciliary beat frequency in the airway epithelium independently of cystic fibrosis transmembrane conductance regulator genotype. OBJECTIVES: To evaluate the efficacy and safety of denufosol in patients with cystic fibrosis who had normal to mildly impaired lung function characteristic of early cystic fibrosis. METHODS: A total of 352 patients greater than or equal to 5 years old with cystic fibrosis who had FEV(1) greater than or equal to 75% of predicted normal were randomized to receive inhaled denufosol, 60 mg, or placebo three times daily in a Phase 3, randomized, double-blind, placebo-controlled, 24-week trial. MEASUREMENTS AND MAIN RESULTS: Main outcome measures included change in FEV(1) from baseline to Week 24 endpoint and adverse events. Mean change from baseline to Week 24 endpoint in FEV(1) (primary efficacy endpoint) was 0.048 L for denufosol (n = 178) and 0.003 L for placebo (n = 174; P = 0.047). No significant differences between groups were observed for secondary endpoints including exacerbation rate and other measures of lung function. Denufosol was well tolerated with adverse event and growth profiles similar to placebo. CONCLUSIONS: Denufosol improved lung function relative to placebo in cystic fibrosis patients with normal to mildly impaired lung function. Clinical trial registered with www.clinicaltrials.gov (NCT00357279).

Treatment of psychological factors in a child with difficult asthma: a case report.

Difficult asthma is defined as the persistence of asthma symptoms, abnormal pulmonary function showing airway obstruction, and continued requirement for short-acting bronchodilator therapy, despite adequate treatment with inhaled corticosteroids. It calls for a thorough evaluation of the patient to look into alternate and complicating diagnoses. The authors report a case of a 9-year-old patient with difficult asthma who failed to respond to conventional therapy. Although it was recognized that he had a number of potential medical complicating factors including allergies, chronic sinusitis, and gastroesophageal reflux, a psychological intervention using hypnosis ultimately appeared to help alleviate his symptoms completely. Thus, psychological evaluation and intervention should be considered early in the course of management of a patient with difficult asthma, because it may help avoid time-consuming and expensive investigations of potential complicating factors, and it may yield rapid improvement in the patient's clinical condition.

Do family mealtime interactions mediate the association between asthma symptoms and separation anxiety?

BACKGROUND: Respiratory problems have been shown to be associated with the development of panic anxiety. Family members play an essential role for children to emotionally manage their symptoms. This study aimed to examine the relation between severity of respiratory symptoms in children with asthma and separation anxiety. Relying on direct observation of family interactions during a mealtime, a model is tested whereby family interactions mediate the relation between asthma severity and separation anxiety symptoms. METHODS: Sixty-three children (ages 9-12 years) with persistent asthma were interviewed via the Diagnostic Interview Schedule for Children IV; family interactions were assessed via direct observation of a mealtime; primary caregivers completed the Childhood Asthma Severity Scale; youth pulmonary function was ascertained with pre- and post-bronchodilator spirometry; adherence to asthma medications was objectively tracked for six weeks. RESULTS: Poorer pulmonary function and higher functional asthma severity were related to higher numbers of separation anxiety symptoms. Controlling for medication adherence, family interaction patterns mediated the relationship between poorer pulmonary function and child separation anxiety symptoms. CONCLUSIONS: Family mealtime interactions may be a mechanism by which respiratory disorders are associated with separation anxiety symptoms in children, potentially through increasing the child's capacity to cognitively frame asthma symptoms as less threatening, or through increasing the child's sense of security within their family relationships.

Understanding dissociation and insight in the treatment of shortness of breath with hypnosis: a case study.

Training in hypnosis is particularly valuable for the physician seeking to better appreciate the interplay between mind and body. Through such experiences the physician can learn that presentation of symptoms often is affected by patients' psychological states, and that symptoms sometimes serve as solutions for patients' psychological dilemmas. The presented case study demonstrates how an 11-year-old's complaint of shortness of breath becomes an opportunity for an appropriately trained physician to provide treatment by helping the patient to engage his inner resources. The case illustrates the strength of hypnosis for accessing resources outside of conscious awareness and use of dissociative language to both support and alter the patient's defenses. We discuss the role of hypnosis when working psychodynamically with a patient, and whether and when insight is important or necessary for change of behavior.

Care for Amish and Mennonite children with cystic fibrosis: a case series.

BACKGROUND: Published articles have described a lack of willingness to allow preventative measures, as well as other types of modern therapies, as an obstacle to providing medical care for Amish and Mennonite populations. METHODS: We present data regarding the 12 Amish and Mennonite patients at the SUNY Upstate Medical University Pediatric Cystic Fibrosis Center and three representative case reports. RESULTS: Families of patients from these communities receiving care at our Center have accepted preventive therapy, acute medical interventions including home intravenous antibiotic administration, and some immunizations for their children with cystic fibrosis, which have improved the health of our patients. Some have even participated in clinical research trials. Health care education for both the child and family is warranted and extensive. Significant Cystic Fibrosis Center personnel time and fundraising are needed in order to address medical bills incurred by uninsured Amish and Mennonite patients. CONCLUSION: Amish and Mennonite families seeking care for cystic fibrosis may choose to utilize modern medical therapies for their children, with resultant significant improvement in outcome.

Sweat chloride testing in infants identified as heterozygote carriers by newborn screening.

The reference ranges for sweat [C1(-)] were reevaluated in 300 infants referred to our Center as carriers of at least 1 cystic fibrosis mutation identified through newborn screening. The recommended borderline range of 30 to 59 mmol/L failed to identify all individuals who were compound heterozygotes. Our data support using a borderline range of 24 to 59 mmol/L.

Subconscious guided therapy with hypnosis.

Two adolescents were hospitalized with incapacitating symptoms: one with headache, back pain, and an inability to walk, while the other had headache, musculoskeletal pain, nausea, and emesis. Medical evaluation did not reveal an etiology for the symptoms of either patient. Consultation with child psychiatry services yielded recommendations that both patients might benefit from counseling. Both demonstrated an immediate improvement of their symptoms with instruction in self-hypnosis-induced relaxation techniques that included favorite place imagery and progressive relaxation. The patients were told that while in hypnosis their "subconscious" might be able to characterize psychological issues that underlay their symptoms through the medium of automatic word processing (AWP). The information identified through AWP helped guide their subsequent therapy. Thus, instruction in self-hypnosis, as well as helping adolescents develop awareness about the cause of their debilitating symptoms can be associated with rapid improvement of their symptoms.

Relationship of headache-associated stressors and hypnosis therapy outcome in children: a retrospective chart review.

This study examined potential psychosocial stressors of 30 children with headaches (mean age, 15 years), and the role of insight generation in the outcome of hypnosis therapy. The mean duration of headache occurrence was 3 years. All of the patients were instructed in how to use hypnosis-induced relaxation and headache-related imagery to improve their symptoms. Thirty-seven percent reported their headaches were associated with fixed stressors, defined as caused by events over which patients had no control, while 63% reported variable stressors, defined as modifiable by the patients' actions. Four patients were lost to follow-up. Overall, 96% (25/26) reported a decrease in headache frequency and/or intensity following use of hypnosis. However, prior to insight generation patients reporting fixed stressors were significantly less likely to improve than those reporting variable stressors (p = 0.018). Thus, insight generation may be more important for achievement of improvement in children whose headaches are associated with fixed stressors.

Inhaled tobramycin solution-associated recurrent eosinophilia and severe persistent bronchospasm in a patient with cystic fibrosis: a case report.

BACKGROUND: Delivery of tobramycin by inhalation to the lungs of patients with cystic fibrosis (CF) who are infected with Pseudomonas aeruginosa has been proven to be effective and safe. The aerosol administration allows high concentrations of tobramycin to be delivered to the site of infection with limited systemic absorption. In rare patients, systemic absorption of inhaled tobramycin may be significant enough to produce toxic effects, such as renal and vestibular toxicities. CASE PRESENTATION: We report a patient with CF who developed recurrent eosinophilia and severe persistent bronchospasm following repeated administration of preservative-free tobramycin by inhalation, beginning at 16 months of age. Also, he developed similar signs and symptoms when he was administered tobramycin intravenously on one occasion at 5 1/2 years. The patient had a history of environmental allergies. Temporal sequence of his signs and symptoms after each administration of tobramycin (similar to re-challenge testing), and his improvement after discontinuation of the drug strongly suggest an adverse drug reaction. CONCLUSION: Hypersensitivity reaction should be considered in patients who develop recurrent eosinophilia and deterioration of pulmonary function following the use of tobramycin by inhalation or by intravenous administration.

Nighttime waking in children with asthma: an exploratory study of daily fluctuations in family climate.

Children with asthma are at increased risk for waking in the night, and there is the potential for the entire household to feel the effects. The authors conducted a telephone-based diary study to examine whether daily fluctuations in parent mood, parenting hassles, and family routines would distinguish nights in which waking occurred from nights in which they did not. Forty-seven families with a child with asthma were contacted 4 times a week every 3 months over a period of 1 year, resulting in 500 daily observations. Parent negative mood, perceived parenting hassles, and disruptions in bedtime routines were associated with increased odds that the child would wake in the middle of the night. Results underscore the importance of considering family climate in children's disturbed sleep.

User friendly hypnosis as an adjunct for treatment of habit cough: a case report.

The more user friendly medical hypnosis can be, the more readily it will be accepted by patients and the medical community. Hypnosis is user friendly when it is simple to employ, and yields rapid, effective, and clinically significant results. Thus, we should define reasons for the effectiveness of such successful hypnosis methods, and provide this information to students of hypnosis. Some of the elements that may permit hypnosis to be user friendly are establishment of rapport, a belief that a symptom often has a functional role, and a flexible approach to the hypnosis encounter. This case report of a child with habit cough, illustrates the importance of these elements.

Persistent Encopresis, Enuresis, and Anxiety in a 7-Year-Old Girl.

CASE: Sonia is a 7-year-old old girl who was referred to the Developmental-Behavioral Pediatrics Clinic by the Pediatric Urology Clinic because of persistent wetting and soiling behaviors. Since age 3 years, she has had a history of encopresis (and wetting) for which she has seen gastroenterology and urology specialists. The mother reports that Sonia has accidents almost daily, and she is not upset when sitting in her urine or feces. She dislikes going into the bathroom or sitting on the toilet by herself. She participated in a behavior modification program associated with the pediatric urology clinic, which helps children learn healthy voiding habits and achieve continence.Sonia also has anxious behaviors. She bites her nails and chews on her hair or shirt. She is afraid of small spaces such as those between the bed and the wall and needs to have stuffed animals cover them. Other instances that trigger her anxious behaviors include loud noises, having a substitute teacher, being separated from her mother, and going to certain bathrooms or new places. She also has severe tantrums, which involve throwing and breaking objects, kicking, and hitting her head against doors.A cognitive behavioral therapy program was recommended to target anxiety symptoms, in addition to timed toileting after meals and polyethylene glycol. At a clinic visit several months later, symptoms of anxiety, encopresis, and enuresis persisted. Cognitive behavior therapy was continued and sertraline 25 mg was prescribed for anxiety. In addition, she was referred to a pediatrician who specializes in relaxation techniques and hypnotherapy.Sonia showed modest improvement with these interventions. There were fewer episodes of angry outbursts and a decrease in soiling and wetting, but at times, but she continued to have intermittent periods of wetting and soiling and fear of going to the bathroom by herself persisted.(This Challenging Case extends observations reviewed in a previous Challenging Case: J Dev Behav Pediatr 2010;531:513-515; DOI: 10.1097/DBP.0b013e3181e5a464.).

Hypnosis for treatment of insomnia in school-age children: a retrospective chart review.

BACKGROUND: The purposes of this study are to document psychosocial stressors and medical conditions associated with development of insomnia in school-age children and to report use of hypnosis for this condition. METHODS: A retrospective chart review was performed for 84 children and adolescents with insomnia, excluding those with central or obstructive sleep apnea. All patients were offered and accepted instruction in self-hypnosis for treatment of insomnia, and for other symptoms if it was felt that these were amenable to therapy with hypnosis. Seventy-five patients returned for follow-up after the first hypnosis session. Their mean age was 12 years (range, 7-17). When insomnia did not resolve after the first instruction session, patients were offered the opportunity to use hypnosis to gain insight into the cause. RESULTS: Younger children were more likely to report that the insomnia was related to fears. Two or fewer hypnosis sessions were provided to 68% of the patients. Of the 70 patients reporting a delay in sleep onset of more than 30 minutes, 90% reported a reduction in sleep onset time following hypnosis. Of the 21 patients reporting nighttime awakenings more than once a week, 52% reported resolution of the awakenings and 38% reported improvement. Somatic complaints amenable to hypnosis were reported by 41%, including chest pain, dyspnea, functional abdominal pain, habit cough, headaches, and vocal cord dysfunction. Among these patients, 87% reported improvement or resolution of the somatic complaints following hypnosis. CONCLUSION: Use of hypnosis appears to facilitate efficient therapy for insomnia in school-age children.