Validity and Cost-Effectiveness of Pediatric Home Respiratory Polygraphy for the Diagnosis of Obstructive Sleep Apnea in Children: Rationale, Study Design, and Methodology.

Obstructive sleep apnea (OSA) in children is a prevalent, albeit largely undiagnosed disease associated with a large spectrum of morbidities. Overnight in-lab polysomnography remains the gold standard diagnostic approach, but is time-consuming, inconvenient, and expensive, and not readily available in many places. Simplified Home Respiratory Polygraphy (HRP) approaches have been proposed to reduce costs and facilitate the diagnostic process. However, evidence supporting the validity of HRP is still scarce, hampering its implementation in routine clinical use. The objectives were: Primary; to establish the diagnostic and therapeutic decision validity of a simplified HRP approach compared to PSG among children at risk of OSA. Secondary: (a) Analyze the cost-effectiveness of the HRP versus in-lab PSG in evaluation and treatment of pediatric OSA; (b) Evaluate the impact of therapeutic interventions based on HRP versus PSG findings six months after treatment using sleep and health parameters and quality of life instruments; (c) Discovery and validity of the urine biomarkers to establish the diagnosis of OSA and changes after treatment.

Increasing Physical Activity in Schools: Strategies for School Health Practitioners.

Background. Colorado passed House Bill 11-1069 in 2011 requiring all public elementary schools to provide students with a minimum of 30 minutes of physical activity (PA) per school day (Physical Activity Expectation in Schools, 2011). The purpose of this article is to describe the results of a 3-year initiative to increase opportunities for PA and to provide recommendations for school health practitioners implementing similar programming. Intervention. In 2014, 13 school districts were funded to increase student PA during school hours and before and after school hours. Intervention activities spanned all components of the Comprehensive School Physical Activity Program framework. An evaluation was conducted to estimate the number of schools providing at least 30 minutes of PA a day. A mixed methods evaluation design was implemented that included tracking the number of minutes of PA provided before, during, and after school and semistructured interviews with school health coordinators. Results. In Year 1, an average of 48 minutes of PA were provided per day. By the end of year 3, the average minutes of PA doubled to 90 minutes per day. Teachers and staff identified professional development and administrator support as key components to incorporating more PA throughout the school day. Conclusions. Health promotion interventions in schools can increase access to PA opportunities for students. Sustainability of PA efforts in schools is dependent on funding to support professional development for teachers and staff and building administrative support for school-based PA.

An Evaluation of an Unstructured and Structured Approach to Increasing Recess Physical Activity.

BACKGROUND: The purpose of this study was to evaluate an unstructured and a structured program designed to increase physical activity (PA). The unstructured program increased the amount of equipment during recess, whereas the structured program introduced activities to students. METHODS: PA was observed using the System for Observing Play and Leisure Activity in Youth (SOPLAY) in two school districts in Colorado. Researchers recorded baseline and follow-up observations for sedentary activity, moderate PA, and vigorous PA, as well as for available equipment for the unstructured program. Observations from schools were aggregated for data analyses at the district level. RESULTS: For the program increasing equipment, moderate PA and vigorous PA increased, while sedentary behavior decreased. For the structured program, moderate PA and vigorous PA did not increase, whereas sedentary behaviors increased following the program. CONCLUSIONS: Other variables are likely influencing student PA during recess, such as teachers' interaction with students or the fidelity of the program. Results indicate that funding and implementing a program aimed at increasing PA will not necessarily accomplish that goal, and additional research should be performed to determine the best practice for increasing PA.

TAZ/WWTR1 Mediates the Pulmonary Effects of NKX2-1 Mutations in Brain-Lung-Thyroid Syndrome.

Context: Identification of a frameshift heterozygous mutation in the transcription factor NKX2-1 in a patient with brain-lung-thyroid syndrome (BLTS) and life-threatening lung emphysema. Objective: To study the genetic defect that causes this complex phenotype and dissect the molecular mechanism underlying this syndrome through functional analysis. Methods: Mutational study by DNA sequencing, generation of expression vectors, site-directed mutagenesis, protein-DNA-binding assays, luciferase reporter gene assays, confocal microscopy, coimmunoprecipitation, and bioinformatics analysis. Results: We identified a mutation [p.(Val75Glyfs*334)] in the amino-terminal domain of the NKX2-1 gene, which was functionally compared with a previously identified mutation [p.(Ala276Argfs*75)] in the carboxy-terminal domain in other patients with BLTS but without signs of respiratory distress. Both mutations showed similar protein expression profiles, subcellular localization, and deleterious effects on thyroid-, brain-, and lung-specific promoter activity. Coexpression of the coactivator TAZ/WWTR1 (transcriptional coactivator with PDZ-binding motif/WW domain-containing transcription regulator protein 1) restored the transactivation properties of p.(Ala276Argfs*75) but not p.(Val75Glyfs*334) NKX2-1 on a lung-specific promoter, although both NKX2-1 mutants could interact equally with TAZ/WWTR1. The retention of residual transcriptional activity in the carboxy-terminal mutant, which was absent in the amino-terminal mutant, allowed the functional rescue by TAZ/WWTR1. Conclusions: Our results support a mechanistic model involving TAZ/WWTR1 in the development of human congenital emphysema, suggesting that this protein could be a transcriptional modifier of the lung phenotype in BLTS.

IGRA testing in patients with immune-mediated inflammatory diseases: which factors influence the results?

Diagnosis of latent tuberculosis infection in patients with immune-mediated inflammatory chronic diseases (IMIDs) can be challenged as diagnostic test reliability could be impaired by immunosuppression. We retrospectively analyzed the Quantiferon Gold-Test in-Tube (QFT-G-IT) results of all patients with IMIDs seen at the Department of Internal Medicine of Son Llàtzer Hospital, Palma de Mallorca (Spain), looking for the factors related to QFT-G-IT indeterminate results. During the study period (2008-2015), 520 patients met the inclusion criteria. Factors associated with indeterminate QFT-G-IT results in a univariate analysis were inflammatory bowel disease, disease activity, lymphopenia, and medium-to-high doses of corticosteroids. In a subsequent multivariate analysis, only lymphopenia (defined as < 1500 cells) was associated with indeterminate QFT-G-IT results. Lymphocyte count was the only factor independently associated with an increased number of indeterminate QFT-G-IT results in patients with different autoimmune diseases. Others factors such as the use of medium-to-high doses of corticosteroids should be considered before testing with QFT-G-IT.

A Method for Evaluating Physical Activity Programs in Schools.

Providing opportunities for students to be physically active during the school day leads to increased academic performance, better focus, and fewer behavioral problems. As schools begin to incorporate more physical activity programming into the school day, evaluators need methods to measure how much physical activity students are being offered through this programming. Because classroom-based physical activity is often offered in 3-minute to 5-minute bouts at various times of the day, depending on the teachers' time to incorporate it, it is a challenge to evaluate this activity. This article describes a method to estimate the number of physical activity minutes provided before, during, and after school. The web-based tool can be used to gather data cost-effectively from a large number of schools. Strategies to increase teacher response rates and assess intensity of activity should be explored.

Intensity of commonly-reported classroom-based physical activity opportunities in public schools.

The purpose of this study was to examine the intensity levels of PA opportunities offered in public school classrooms. Schools (N = 101) in school districts (N = 25) reported PA opportunities offered in classrooms using an online data collection tool over a two-year period (2014-2016). Using a randomized sampling technique, 20-30% of teachers in each school were selected each week to report PA in their classroom. These responses resulted in N = 18,210 usable responses. A researcher determined the intensity of PA opportunities using the 2011 Compendium of Physical Activities as a guideline; two additional researchers confirmed the coded categories. A descriptive analysis of PA opportunities was conducted to describe the proportion of opportunities whose intensity levels were light (LPA), moderate (MPA), vigorous (VPA), sedentary (SED), and those of unknown intensity. Chi-square analyses were utilized to examine differences between proportions of intensity levels offered by semester. Kruskal-Wallace tests were utilized to examine differences in proportion of physical activity opportunity intensity offered by grade level. Most PA opportunities were MPA (58.7%), followed by VPA (17.6%) and LPA (11.5%). Few responses were SED (0.5%), and 11.6% were of indeterminate intensity. A greater proportion of more physically intense activities reported during the fall versus spring semesters (p < 0.0001). Differences in the intensity levels of PA offered by grade also differed, with a trend of decreasing intensity as grade level increased (p < 0.0001). This study provides insight into the PA actually occurring in classrooms; a previously underexplored construct of school-based PA.

Initial experience with a new biodegradable airway stent in children: Is this the stent we were waiting for?

OBJECTIVE: To report our experience with a new type of biodegradable airway stent in the setting of severe tracheobronchial obstruction in children. DESIGN AND METHODOLOGY: We conducted a retrospective and prospective (since June 2014) study of pediatric patients with severe airway obstruction treated with biodegradable stents in our institution between 2012 and 2015. The following data were collected: demographics, indication for stenting, bronchoscopic findings, insertion technique complications, clinical outcome, stent related complications, re-stenting, and time of follow-up. RESULTS: Thirteen custom-made polydioxanone stents were placed in four infants (mean age, 4 months) with severe tracheobronchial obstruction: tracheomalacia (two patients), bronchomalacia (1), and diffuse tracheal stenosis (1). All the stents were bronchoscopically inserted uneventfully. Immediate and maintained clinical improvement was observed in every case. No major stent related complications have occurred and only mild or moderate granulation tissue was observed during surveillance bronchoscopy. Two patients required repeated stenting as expected. All the patients are alive and in a good respiratory condition with a follow-up ranging from 5 to 40 months. CONCLUSIONS: Biodegradable airway stents seem to be safe, effective, and cause fewer complications than other types of stents. They can be an alternative to the classic metallic or plastic stents for severe tracheal stenosis or malacia in small children. More experience is needed in order to establish the definite clinical criteria for their use in pediatric patients. Pediatr Pulmonol. 2016;51:607-612. © 2015 Wiley Periodicals, Inc.

Role of QuantiFERON(®)-TB Gold In-Tube in tuberculosis contact investigation: experience in a tuberculosis unit.

BACKGROUND: Interferon-γ release assays (IGRAs) are increasingly used for the diagnosis of latent tuberculosis infection (LTBI). Because of the lack of a gold standard for the diagnosis of LTBI, IGRAs are compared to the tuberculin skin test (TST) and yield conflicting results. We assessed the usefulness of an IGRA test, QuantiFERON(®)-TB Gold In-Tube (QFT-G-IT), for diagnosing LTBI compared with TST in the setting of a contact screening study. METHODS: A prospective comparison between the QFT-G-IT and the TST in TB contact subjects in a low TB burden area was conducted sequentially between January 2006 and December 2012. RESULTS: A moderate concordance between the two tests (κ = 0.44 for TST cut-off of 5 mm and κ = 0.56 for TST cut-off of 15 mm) was found. A better agreement was shown in younger contacts and in non-vaccinated contacts when using a TST of 15 mm. Independent risk factors for a TST(+)/QFT-G-IT(-) discordance were history of BCG vaccination and age between 31 and 59 years. Discordance was also more frequent using a TST cut-off value of 5 mm. QFT-G-IT(+)/TST(-) was infrequent and was found in older contacts. CONCLUSIONS: Based on our data, we cannot recommend the use of QFT-G-IT as the only test to rule out LTBI, especially in older patients.

Treatment strategies in the management of severe complications following slide tracheoplasty in children.

OBJECTIVES: This study focuses on the different surgical and endoscopical treatment alternatives when dealing with severe complications after slide tracheoplasty (STP). METHODS: Retrospective study of patients with symptomatic congenital tracheal stenosis (CTS) admitted to a single institution, between January 1997 and January 2013, surgically treated by means of STP. The following variables were evaluated: demographics, preoperative tracheal stenosis characteristics, associated anomalies and outcome measures. RESULTS: Cohort included 14 patients (8 males and 6 females) with a mean age of 8.7 months when treated (range, 1-43 m). Eleven patients (78%) showed a long segment CTS (>30% of total tracheal length) and 9 (64%) had associated cardiac or great vessel anomalies (left pulmonary artery sling). Three patients (21%) showed severe postoperative complications that required significant airway reintervention: tracheal resection of a restenotic segment, laser division with balloon dilatation of a residual stenosis and placement of a biodegradable endotracheal stent in an extensive tracheal narrowing. All patients are in good clinical condition with a mean follow-up of 6.3 years (range, 2 months to 16 years). CONCLUSIONS: STP has become the procedure of choice when dealing with CTS. Although it shows clear advantages compared with other surgical techniques, severe and difficult to manage complications may occur. Surgeons involved in their treatment should be familiar with diverse surgical and endoscopical procedures. Biodegradable airway stenting is a new and promising technique when long and severe post-surgical tracheal stenosis is present.

[Symptomatic acute Q fever: a series of 87 cases in an area of Mallorca]. / Fiebre Q aguda sintomática: 87 casos en un área de Mallorca.

INTRODUCTION: Q fever is a widespread zoonotic infection caused by Coxiella burnetii (C. burnetii). Acute infection varies from a self-limited flu-like illness to pneumonia or hepatitis. METHODS: A retrospective case study from March 2003 to December 2011 was conducted in the Hospital Son Llàtzer in Palma de Mallorca. Acute Q-fever was diagnosed in a patient with clinical suspicion and IgM in phase ii positive (≥ 1/40), with a positive IgG (≥1/80), or when IgG seroconversion was observed during convalescence. A total of 87 cases of acute Q fever were diagnosed. The median age was 50 years (range 21-89), and 69 (79.3%) were male. Fever and headache were the most common symptoms. Pneumonia was diagnosed in 39 (44.8%) patients, febrile episode in 21 (24.1%), and acute hepatitis in 23 (25.6%). Increased serum transaminases were observed in 19 (21.8%). Doxycycline was prescribed in 29 cases (33.4%). There were 30 (34.5%) patients lost to follow up after hospital discharge. A favorable outcome was observed in all other cases. Only one new case progressed to chronic Q fever. RESULTS: A total of 87 cases of acute Q fever were diagnosed. The median age was 50 years (range 21-89), and 69 (79.3%) were male. Fever and headache were the most common symptoms. Pneumonia was diagnosed in 39 (44.8%) patients, febrile episode in 21 (24.1%), and acute hepatitis in 23 (25.6%). Increased serum transaminases were observed in 19 (21.8%). Doxycycline was prescribed in 29 cases (33.4%). There were 30 (34.5%) patients lost to follow up after hospital discharge. A favorable outcome was observed in all other cases. Only one new case progressed to chronic Q fever. CONCLUSION: Acute Q fever acute is common our environment. Pneumonia was the most common clinical presentation. Even although doxycycline was prescribed in a small number of patients, a favorable outcome was observed in all cases.

Experience of a monographic tuberculosis unit: the first 500 cases.

INTRODUCTION: Tuberculosis (TB) remains a highly prevalent and potentially severe disease. However, since 2002 the annual incidence has been decreasing both worldwide and in Spain, where the incidence varies widely between regions. The main objective of this study is to describe the experience of a monographic TB unit in a second level hospital. PATIENTS AND METHODS: A descriptive study was carried out which included all cases of TB diagnosed in a monographic unit of a secondary hospital between 2003 and 2011. Demographic, clinical, epidemiological and microbiological data were recorded. RESULTS: We analyzed 500 TB cases and found an increasing annual incidence in all subgroups, including native and immigrant populations. Most cases (63.8%) were male, with a median age of 36 years (range 8 months-90 years). In total, 39.8% of patients were foreign born. Coinfection with human immunodeficiency virus was found in 11% of cases. The pulmonary form was most frequently diagnosed (63.8%). Overall mortality was 5.8% with no significant differences between groups (including foreign born and human immunodeficiency virus positive patients). CONCLUSIONS: Although TB incidence is globally decreasing, in our study we found an increasing number of cases in recent years in all subgroups, which can be explained by this being a monographic unit with an intensive contact tracing program.

Use of Quantiferon-TB-Gold in Tube(®) test for detecting latent tuberculosis in patients considered as candidates for anti-TNF therapy in routine clinical practice.

BACKGROUND/METHODS: Quantiferon-TB-Gold in Tube(®) test (QFT-G-IT) may have advantages if combined with TST when screening for Latent Tuberculosis Infection (LTBI) prior to initiating anti-TNF therapy in an area of intermediate tuberculosis incidence such as Spain. In a small-scale prospective study, we evaluate the use of QFT-G-IT in combination with the screening recommended in Spain (Tuberculin-Skin Test, TST retest, clinical data, and Chest X-Ray (CXR)) for LTBI in patients considered as candidates for anti-TNFα treatment. RESULTS: From June 2008 to October 2010, 123 patients from a 300-bed hospital in Palma de Mallorca (Spain) were included in the study. The majority of patients were under immunosuppressive therapy. A positive TST and TST booster were found in 22 and 17 patients, respectively. Thus 39 (31.7%) of the 123 patients had a positive TST. QFT-G-IT was positive in 16 patients (13.6%), indeterminate in 4 (3.2%), and negative in 103 (83.7%). One of the two tests was positive and LTBI was diagnosed in 34.1% of patients. The agreement between TST and QFT-G-IT among vaccinated patients was low and not statistically significant (Kappa=0.15) and was almost perfect among non-BCG vaccinated patients (K=0.81). TST positive responses were significantly related to BCG-vaccination (p<0.05) and QFT-G-IT positive response rates were related to older age (p<0.05). CONCLUSION: QFT-G-IT may have advantages when combined with TST in immunosuppressed patients especially in older patients with a negative TST; in BCG vaccinated patients with a positive TST, QFT-G-IT could avoid unnecessary treatments and toxicities related to a false-positive TST result.

Paediatric patients with a tracheostomy: a multicentre epidemiological study.

Changes in the indications for tracheostomy in children have led to the progressively greater involvement of the paediatric pulmonologist in the care of these patients. The aim of this study was to review the current profile of tracheostomised children in Spain. We undertook a longitudinal, multicentre study over 2 yrs (2008 and 2009) of all patients aged between 1 day and 18 yrs who had a tracheostomy. The study, involving 18 Spanish hospitals, included 249 patients, of whom 150 (60.2%) were <1 yr of age. The main indications for the procedure were prolonged ventilation (n=156, 62.6%), acquired subglottic stenosis (n=34, 13.6%), congenital or acquired craniofacial anomalies (n=25, 10%) and congenital airway anomalies (n=24, 9.6%). The most frequent underlying disorders were neurological diseases (n=126, 50.6%) and respiratory diseases (n=98, 39.3%). Over the 2-yr study period, 92 (36.9%) children required ventilatory support, and decannulation was achieved in 59 (23.7%). Complications arose in 117 patients (46.9%). Mortality attributed to the underlying condition was 12.5% and that related directly to the tracheostomy was 3.2%. Respiratory complexity of tracheostomised children necessitates prolonged, multidisciplinary follow-up, which can often extend to adulthood.

[Quantiferon-TB Gold In-Tube test in the diagnosis of pulmonary and extra-pulmonary tuberculosis]. / Valor de QuantiFERON-TB Gold Test in Tube en el diagnóstico de tuberculosis pulmonar y extrapulmonar.

INTRODUCTION: The Interferon-γ in vitro detection tests could be a useful tool in the diagnosis of active tuberculosis compared to Mycobacterium tuberculosis (MTB). METHODS: The QuantiFERON-TB-Gold in Tube (QFG-IT) test was performed on the blood of 118 patients with active tuberculosis and the results compared with the tuberculin test. RESULTS: The QFG-IT test was positive in 94 cases (79.7%), negative in 17 (14.4%) and indeterminate in 7 (5.9%). A negative or indeterminate QFG-IT test was more common in older patients (P=0.017) and in cases with negative smear tests (P=0.041). The kappa agreement between the tuberculin and QFG-IT tests was 74.5% with a kappa value of 0.45 (SE:0.136). Thirteen of the patients studied were infected with HIV and the tuberculin was positive in 5 of the 12 cases (38.5%) in whom it was performed, with the QFG-IT being positive in 9/13 (69.2%). CONCLUSIONS: The QFG-IT test may be a useful complimentary tool to the tuberculin test in the diagnosis of tuberculosis.

Development of low-cost inverted microscope to detect early growth of Mycobacterium tuberculosis in MODS culture.

BACKGROUND: The microscopic observation drug susceptibility (MODS) assay for rapid, low-cost detection of tuberculosis and multidrug resistant tuberculosis depends upon visualization of the characteristic cording colonies of Mycobacterium tuberculosis in liquid media. This has conventionally required an inverted light microscope in order to inspect the MODS culture plates from below. Few tuberculosis laboratories have this item and the capital cost of $5,000 for a high-end microscope could be a significant obstacle to MODS roll-out. METHODOLOGY: We hypothesized that the precise definition provided by costly high-specification inverted light microscopes might not be necessary for pattern recognition. SIGNIFICANCE: In this work we describe the development of a low-cost artesenal inverted microscope that can operate in both a standard or digital mode to effectively replace the expensive commercial inverted light microscope, and an integrated system that could permit a local and remote diagnosis of tuberculosis.

Can the power of mobile phones be used to improve tuberculosis diagnosis in developing countries?

The low-cost Microscopic Observation Drug Susceptibility (MODS) assay is a non-proprietary test that delivers rapid and accurate diagnosis of tuberculosis (TB) and multidrug-resistant TB. Although methodologically straightforward, implementation is challenging in isolated settings where personnel trained in plate reading are lacking. One affordable strategy to address this shortfall is the use of mobile phones, first to transmit images captured by an inverted microscope to a remote site where pattern recognition is performed by trained personnel, and second to receive the resulting output of this analysis. Such a system could be used for training of laboratory personnel through distance learning, resolution of equivocal appearances and quality assurance.