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BACKGROUND: Helios (encoded by IKZF2), a member of the Ikaros family of transcription factors, is a zinc finger protein involved in embryogenesis and immune function. Although predominantly recognised for its role in the development and function of T lymphocytes, particularly the CD4+ regulatory T cells (Tregs), the expression and function of Helios extends beyond the immune system. During embryogenesis, Helios is expressed in a wide range of tissues, making genetic variants that disrupt the function of Helios strong candidates for causing widespread immune-related and developmental abnormalities in humans. METHODS: We performed detailed phenotypic, genomic and functional investigations on two unrelated individuals with a phenotype of immune dysregulation combined with syndromic features including craniofacial differences, sensorineural hearing loss and congenital abnormalities. RESULTS: Genome sequencing revealed de novo heterozygous variants that alter the critical DNA-binding zinc fingers (ZFs) of Helios. Proband 1 had a tandem duplication of ZFs 2 and 3 in the DNA-binding domain of Helios (p.Gly136_Ser191dup) and Proband 2 had a missense variant impacting one of the key residues for specific base recognition and DNA interaction in ZF2 of Helios (p.Gly153Arg). Functional studies confirmed that both these variant proteins are expressed and that they interfere with the ability of the wild-type Helios protein to perform its canonical function-repressing IL2 transcription activity-in a dominant negative manner. CONCLUSION: This study is the first to describe dominant negative IKZF2 variants. These variants cause a novel genetic syndrome characterised by immunodysregulation, craniofacial anomalies, hearing impairment, athelia and developmental delay.
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Anomalías Craneofaciales , Discapacidades del Desarrollo , Pérdida Auditiva , Factor de Transcripción Ikaros , Humanos , Proteínas de Unión al ADN/genética , Factor de Transcripción Ikaros/genética , Síndrome , Discapacidades del Desarrollo/genética , Anomalías Craneofaciales/genéticaRESUMEN
This practice point summarizes recommendations from the Canadian Thoracic Society's 2021 "Guideline update: Diagnosis and management of asthma in preschoolers, children, and adults." New recommendations include: a decrease in the frequency of daytime symptoms and reliever use to ≤2 per week in the asthma control criteria; assessing for risk of asthma exacerbation; not using as-needed short-acting beta-agonists alone in patients at higher risk for exacerbation; and the option of as-needed budesonide/formoterol (bud/form) in those ≥12 years old if they are unable to take daily inhaled corticosteroids despite extensive asthma education and support. The preference for daily inhaled corticosteroids to manage mild asthma in children, and the recommendation against intermittent short courses of inhaled corticosteroids, are unchanged.
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Le présent point de pratique résume la mise à jour des lignes directrices de la Société canadienne de thoracologie publiée en 2021 sur le diagnostic et la prise en charge de l'asthme chez les enfants d'âge préscolaire, les enfants et les adultes. Ces nouvelles recommandations incluent, parmi les critères de contrôle de l'asthme, une diminution de la fréquence des symptômes diurnes et de l'utilisation de médicaments pour soulager l'asthme à un maximum de deux fois par semaine. Elles comprennent également l'évaluation du risque d'exacerbation de l'asthme, la non-utilisation de bêta-agonistes à courte durée d'action seuls au besoin chez les patients à plus fort risque d'exacerbation et la possibilité d'administrer du budésonide-formotérol au besoin aux jeunes de 12 ans ou plus qui sont incapables de prendre des corticostéroïdes inhalés au quotidien malgré une éducation sur l'asthme et un soutien importants. La préférence pour la prise quotidienne de corticostéroïdes inhalés afin de traiter l'asthme léger chez les enfants et la recommandation d'éviter les courts traitements intermittents de corticostéroïdes inhalés ne changent pas.
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Background: The COVID-19 pandemic required a rapid expansion of teledermatology services. Objective: Analyze demographic shifts in a pediatric dermatology practice session with children of color. Methods: A retrospective chart review of pediatric dermatology patients seen in the 4 practice weeks preceding the New York COVID-19 lockdown and comparable teledermatology visits during the COVID-19 pandemic lockdown. Demographic differences (e.g., race, age, gender, and household income) were analyzed. Results: A greater proportion of patients seen were White during lockdown (59.7%), compared with pre-lockdown (43.6%), with a reduction in Asian patients seen in lockdown (6.0%) compared with pre-lockdown (24.5%). A lower proportion of no-show patients (4.3%, 3/70 scheduled) were noted in lockdown compared with pre-lockdown (16%, 18/112). Preferred provider organizations (PPO) and higher-income zip codes were more common for children seen during lockdown. Limitations: The sample addresses a limited New York pediatric dermatology practice during a short time period. Conclusions: White patients and patients with PPO were more likely to access telehealth, supporting disparity in teledermatology services. These results demonstrate reduced health care access for lower-income and Asian children during the COVID-19 pandemic lockdown.
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COVID-19 , Dermatología , Telemedicina , Niño , Humanos , Dermatología/métodos , COVID-19/epidemiología , Estudios Retrospectivos , Pandemias , Control de Enfermedades Transmisibles , Telemedicina/métodosRESUMEN
OBJECTIVE: To highlight recommendations from the Canadian Thoracic Society (CTS) 2021 asthma guideline for adults and children aged 12 years and older and to address controversies related to the update. SOURCES OF INFORMATION: The CTS 2021 asthma guideline. MAIN MESSAGE: Asthma is a common condition encountered in primary care. Poor symptom control and exacerbations contribute substantially to the burden of disease. Practice guidelines have been shifting in recent years toward more aggressive treatment of very mild and mild asthma, with goals of optimizing symptom control and reducing exacerbations. Consider underlying risk of exacerbation, extent of asthma symptoms, adherence levels, and treatment cost when choosing therapy for patients with very mild and mild asthma. CONCLUSION: The goal of this article is to briefly review the evidence and rationale behind treatment options in the CTS guideline to help physicians make patient-centred decisions.
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Asma , Médicos , Niño , Adulto , Humanos , Canadá , Asma/tratamiento farmacológicoRESUMEN
Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has impacted healthcare services and outcomes. We aimed to investigate healthcare resource utilization and early health outcomes of infants born to mothers with perinatal SARS-CoV-2 infection. Methods: The study included all infants born alive between February 1, 2020, and April 30, 2021, in British Columbia. We used linked provincial population-based databases including data on COVID-19 testing, birth, and health information for up to one year from birth. Perinatal COVID-19 exposure for infants was defined being born to mothers with a positive test for SARS-CoV-2 infection during pregnancy or at delivery. Cases of COVID-19-exposed infants were matched with up to four non-exposed infants by birth month, sex, birthplace, and gestational age in weeks. Outcomes included hospitalizations, emergency department visits, and in-/outpatient diagnoses. Outcomes were compared between groups using conditional logistic regression and linear mixed effects models including effect modification by maternal residence. Results: Among 52,711 live births, 484 infants had perinatal exposure to SARS-CoV-2, an incidence rate of 9.18 per 1000 live births. Exposed infants (54.6% male) had a mean gestational age of 38.5 weeks, and 99% were born in hospital. Proportions of infants requiring at least one hospitalization (8.1% vs. 5.1%) and at least one emergency department visit (16.9% vs. 12.9%) were higher among the exposed vs. unexposed infants, respectively. Among infants from the urban area, those with exposure were more likely to have respiratory infectious diseases (odds ratio: 1.74; 95% confidence intervals: 1.07, 2.84), compared with those without exposure. Interpretation. In our cohort, infants born to mothers with SARS-CoV-2 infection have increased healthcare demands in their early infancy, which warrants further investigation.
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BACKGROUND: Community-based health care (CBHC) is a shift towards healthcare integration and community services closer to home. Variation in system approaches harkens the need for a conceptual framework to evaluate outcomes and impacts. We set out to develop a CBHC-specific evaluation framework in the context of a provincial ministry of health planning process in Canada. METHODS: A multi-step approach was used to develop the CBHC evaluation framework. Modified Delphi informed conceptualization and prioritization of indicators. Formative research identified evaluation framework elements (triple aim, global measures, and impact), health system levels (tiers), and potential CBHC indicators (n = 461). Two Delphi rounds were held. Round 1, panelists independently ranked indicators on CBHC relevance and health system tiering. Results were analyzed by coding agreement/disagreement frequency and central tendency measures. Round 2, a consensus meeting was used to discuss disagreement, identify Tier 1 indicators and concepts, and define indicators not relevant to CBHC (Tier 4). Post-Delphi, indicators and concepts were refined, Tier 1 concepts mapped to the evaluation framework, and indicator narratives developed. Three stakeholder consultations (scientific, government, and public/patient communities) were held for endorsement and recommendation. RESULTS: Round 1 Delphi results showed agreement for 300 and disagreement for 161 indicators. Round 2 consensus resulted in 103 top tier indicators (Tier 1 = 19, Tier 2 = 84), 358 bottom Tier 3 and 4 indicators, non-CBHC measure definitions, and eight Tier 1 indicator concepts-Mortality/Suicide; Quality of Life, and Patient Reported Outcome Measures; Global Patient Reported Experience Measures; Cost of Care, Access to Integrated Primary Care; Avoidable Emergency Department Use; Avoidable Hospitalization; and E-health Penetration. Post Delphi results refined Tier 3 (n = 289) and 4 (n = 69) indicators, and identified 18 Tier 2 and 3 concepts. When mapped to the evaluation framework, Tier 1 concepts showed full coverage across the elements. 'Indicator narratives' depicted systemness and integration for evaluating CBHC. Stakeholder consultations affirmed endorsement of the approach and evaluation framework; refined concepts; and provided key considerations to further operationalize and contextualize indicators, and evaluate CBHC as a health system approach. CONCLUSIONS: This research produced a novel evaluation framework to conceptualize and evaluate CBHC initiatives. The evaluation framework revealed the importance of a health system approach for evaluating CBHC.
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Servicios de Salud Comunitaria , Calidad de Vida , Atención a la Salud , Técnica Delphi , Programas de Gobierno , Humanos , Indicadores de Calidad de la Atención de SaludRESUMEN
BACKGROUND: Dornase alfa is currently used as a mucolytic to treat pulmonary disease (the major cause of morbidity and mortality) in cystic fibrosis. It reduces mucus viscosity in the lungs, promoting improved clearance of secretions. This is an update of a previously published review. OBJECTIVES: To determine whether the use of dornase alfa in cystic fibrosis is associated with improved mortality and morbidity compared to placebo or other medications that improve airway clearance, and to identify any adverse events associated with its use. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises references identified from comprehensive electronic database searches, handsearching relevant journals and abstracts from conferences. Date of the most recent search of the Group's Cystic Fibrosis Register: 12 October 2020. Clinicaltrials.gov and the International Clinical Trials Registry Platform were also searched to identify unpublished or ongoing trials. Date of most recent search: 08 February 2021. SELECTION CRITERIA: All randomised and quasi-randomised controlled trials comparing dornase alfa to placebo, standard therapy or other medications that improve airway clearance. DATA COLLECTION AND ANALYSIS: Authors independently assessed trials against the inclusion criteria; two authors carried out analysis of methodological quality and data extraction. GRADE was used to assess the level of evidence. MAIN RESULTS: The searches identified 74 trials, of which 19 (2565 participants) met our inclusion criteria. 15 trials compared dornase alfa to placebo or no dornase alfa (2447 participants); two compared daily dornase to hypertonic saline (32 participants); one compared daily dornase alfa to hypertonic saline and alternate day dornase alfa (48 participants); one compared dornase alfa to mannitol and the combination of both drugs (38 participants). Trial duration varied from six days to three years. Dornase alfa compared to placebo or no treatment Dornase alfa probably improved forced expiratory volume at one second (FEV1) at one month (four trials, 248 participants), three months (one trial, 320 participants; moderate-quality evidence), six months (one trial, 647 participants; high-quality evidence) and two years (one trial, 410 participants). Limited low-quality evidence showed treatment may make little or no difference in quality of life. Dornase alfa probably reduced the number of pulmonary exacerbations in trials of up to two years (moderate-quality evidence). One trial that examined the cost of care, including the cost of dornase alfa, found that the cost savings from dornase alfa offset 18% to 38% of the medication costs. Dornase alfa: daily versus alternate day One cross-over trial (43 children) found little or no difference between treatment regimens for lung function, quality of life or pulmonary exacerbations (low-quality evidence). Dornase alfa compared to other medications that improve airway clearance Results for these comparisons were mixed. One trial (43 children) showed dornase alfa may lead to a greater improvement in FEV1 compared to hypertonic saline (low-quality evidence), and one trial (23 participants) reported little or no differences in lung function between dornase alfa and mannitol or dornase alfa and dornase alfa plus mannitol (low-quality evidence). One trial (23 participants) found dornase alfa may improve quality of life compared to dornase alfa plus mannitol (low-quality evidence); other comparisons found little or no difference in this outcome (low-quality evidence). No trials in any comparison reported any difference between groups in the number of pulmonary exacerbations (low-quality evidence). When all comparisons are assessed, dornase alfa did not cause significantly more adverse effects than other treatments, except voice alteration and rash. AUTHORS' CONCLUSIONS: There is evidence to show that, compared with placebo, therapy with dornase alfa may improve lung function in people with cystic fibrosis in trials lasting from one month to two years. There was a decrease in pulmonary exacerbations in trials of six months or longer, probably due to treatment. Voice alteration and rash appear to be the only adverse events reported with increased frequency in randomised controlled trials. There is not enough evidence to firmly conclude if dornase alfa is superior to other hyperosmolar agents in improving lung function.
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Fibrosis Quística/tratamiento farmacológico , Desoxirribonucleasa I/uso terapéutico , Expectorantes/uso terapéutico , Adolescente , Adulto , Niño , Preescolar , Desoxirribonucleasa I/efectos adversos , Progresión de la Enfermedad , Expectorantes/efectos adversos , Volumen Espiratorio Forzado , Humanos , Lactante , Manitol/uso terapéutico , Placebos/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como Asunto , Proteínas Recombinantes/efectos adversos , Proteínas Recombinantes/uso terapéutico , Solución Salina Hipertónica/uso terapéutico , Capacidad VitalRESUMEN
BACKGROUND/OBJECTIVES: Little research has compared clinician acne severity assessment with either adolescent- or parent-rated scales of acne severity or impact on quality of life (QOL). We sought to assess how adolescents and their parents perceive the severity and impact of acne on the adolescent's QOL and correlate this with clinical severity. METHODS: Each adolescent and a parent completed a validated QOL survey regarding the adolescent's acne and rated the adolescent's acne severity and QOL impact using a Likert scale. Clinicians assessed the adolescent's acne using a standardized acne severity scale. Statistical analysis compared adolescent scores with respective parent scores or with clinician assessment using a paired t test or Spearman rank-order correlation test. RESULTS: The Likert impact score more accurately reflected acne impact on QOL for adolescents than for parents when considering the validated QOL survey as the gold standard (r2 = .56 vs r2 = .36). Likert scores for adolescents and parents were weakly correlated for acne severity but not for acne QOL impact (r2 = .36 vs r2 = .18). Correlations of acne severity scores between clinician and either adolescent or parent were weak. CONCLUSIONS: Parents and adolescents are in relative agreement regarding acne severity and QOL impact. However, parent and adolescent perceptions are disparate from clinician acne assessment. It is important that physicians identify and consider adolescent and parent perceptions in addition to clinical assessment to better inform the approach to acne management.
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Acné Vulgar , Calidad de Vida , Adolescente , Humanos , Padres , Percepción , Índice de Severidad de la Enfermedad , Encuestas y CuestionariosRESUMEN
BACKGROUND: Medical schools rarely offer exposure to clinical dermatology in the first-year curriculum. OBJECTIVE: We describe and report student satisfaction results of three novel teaching methods for integrating basic dermatology concepts into gross anatomy laboratory. METHODS: During the first year of the intervention, 180 students attended an hour-long anatomy laboratory session during which skin lesions were examined. One attending and three resident dermatologists spent time at all tables of students, then circulated to answer questions. During the second year, 189 students participated in the same teaching session preceded by a 30-minute in-class lecture. During the third year, 172 students were given the option to view a supplemental online video module before or after the teaching session. Each year following the teaching session students were sent an optional online survey regarding the impact of the teaching session on their understanding of skin lesions and their cadaver experience. RESULTS: Overall, students believed the intervention helped them develop a better understanding and appreciation for dermatology. Preceding the laboratory session with a lecture or educational video yielded higher satisfaction scores. CONCLUSIONS: This brief teaching intervention illustrates an approach to introducing dermatologic entities within the foundational science curriculum of the first year of medical school.
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Anatomía/educación , Dermatología/educación , Educación de Pregrado en Medicina/métodos , Boston , Humanos , Estudiantes de Medicina , Encuestas y CuestionariosAsunto(s)
Alopecia , Cicatriz , Doxiciclina , Humanos , Estudios Retrospectivos , Alopecia/tratamiento farmacológico , Doxiciclina/uso terapéutico , Femenino , Masculino , Adulto , Cicatriz/etiología , Cicatriz/tratamiento farmacológico , Persona de Mediana Edad , Antibacterianos/uso terapéutico , Resultado del Tratamiento , Adulto Joven , AncianoRESUMEN
BACKGROUND: Prior to introducing social needs screening into our subspecialty clinics, we first wanted to understand the health effects of the major social challenges facing children with chronic diseases in British Columbia. METHODS: Using a strict prospective methodology, avoiding use of health databases and proxy end points, we studied the effects of five social health determinants (distance from care, family income, gender, ethnicity, caregiver education), on health outcomes in three groups of children with chronic diseases: cystic fibrosis (CF), type 1 diabetes (T1D), chronic kidney disease (CKD). Social determinant data were collected at a face-to-face interview during a clinic visit. These were correlated with diagnosis-specific health outcomes, measured at the same visit. Main outcomes were: forced expired volume in 1 second (FEV1) (CF group), HbA1c (T1D group), estimated glomerular filtration rate (CKD group). RESULTS: We studied 270 children: 85 CF, 89 T1D and 96 CKD. In all three groups, children from families with annual income less than $45,000 had significantly worse health than those from families above this cut-off. Lower caregiver education was related to worse health in the CKD and T1D groups. We found no adverse health effects associated with distance from subspecialty care, patient ethnicity or gender. CONCLUSION: Even in a prosperous province, family poverty and lack of caregiver education still impose measurable adverse effects on the health of children with chronic diseases. We hope these results help support the integration of social needs screening into routine multidisciplinary outpatient clinics. Early detection of social problems and targeted interventions will hopefully help to equalize health outcomes between children from different social groups.
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BACKGROUND: Dornase alfa is currently used as a mucolytic to treat pulmonary disease (the major cause of morbidity and mortality) in cystic fibrosis. It reduces mucus viscosity in the lungs, promoting improved clearance of secretions. This is an update of a previously published review. OBJECTIVES: To determine whether the use of dornase alfa in cystic fibrosis is associated with improved mortality and morbidity compared to placebo or other medications that improve airway clearance, and to identify any adverse events associated with its use. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises references identified from comprehensive electronic database searches, handsearching relevant journals and abstracts from conferences. Date of the most recent search of the Group's Cystic Fibrosis Register: 23 April 2018.Clinicaltrials.gov and the International Clinical Trials Registry Platform were also searched to identify unpublished or ongoing trials. Date of most recent search: 07 June 2018. SELECTION CRITERIA: All randomised and quasi-randomised controlled trials comparing dornase alfa to placebo, standard therapy or other medications that improve airway clearance. DATA COLLECTION AND ANALYSIS: Authors independently assessed trials against the inclusion criteria; two authors carried out analysis of methodological quality and data extraction. GRADE was used to assess the level of evidence. MAIN RESULTS: The searches identified 69 trials, of which 19 (2565 participants) met our inclusion criteria. Fifteen trials compared dornase alfa to placebo or no dornase alfa (2447 participants); two compared daily dornase to hypertonic saline (32 participants); one compared daily dornase alfa to hypertonic saline and alternate day dornase alfa (48 participants); one compared dornase alfa to mannitol and the combination of both drugs (38 participants). Trial duration varied from six days to three years.Dornase alfa compared to placebo or no treatmentDornase alfa improved forced expiratory volume at one second at one month (four trials, 248 participants), three months (one trial, 320 participants; moderate-quality evidence), six months (one trial, 647 participants; high-quality evidence) and two years (one trial, 410 participants). Limited low-quality evidence showed no difference between groups for changes in quality of life. There was a decrease in pulmonary exacerbations with dornase alfa in trials of up to two years (moderate-quality evidence). One trial that examined the cost of care, including the cost of dornase alfa, found that the cost savings from dornase alfa offset 18% to 38% of the medication costs.Dornase alfa: daily versus alternate dayOne cross-over trial (43 children) found no differences between treatment regimens for lung function, quality of life or pulmonary exacerbations (low-quality evidence).Dornase alfa compared to other medications that improve airway clearanceResults for these comparisons were mixed. One trial (43 children) showed a greater improvement in forced expiratory volume at one second for dornase alfa compared to hypertonic saline (low-quality evidence), and one trial (23 participants) reported no difference in lung function between dornase alfa and mannitol or dornase alfa and dornase alfa plus mannitol (low-quality evidence). One trial (23 participants) found a difference in quality of life favouring dornase alfa when compared to dornase alfa plus mannitol (low-quality evidence); other comparisons found no difference in this outcome (low-quality evidence). No trials in any comparison reported any difference between groups in the number of pulmonary exacerbations (low-quality evidence).When all comparisons are assessed, dornase alfa did not cause significantly more adverse effects than other treatments, except voice alteration and rash. AUTHORS' CONCLUSIONS: There is evidence to show that, compared with placebo, therapy with dornase alfa improves lung function in people with cystic fibrosis in trials lasting from one month to two years. There was a decrease in pulmonary exacerbations in trials of six months or longer. Voice alteration and rash appear to be the only adverse events reported with increased frequency in randomised controlled trials. There is not enough evidence to firmly conclude if dornase alfa is superior to other hyperosmolar agents in improving lung function.
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Fibrosis Quística/tratamiento farmacológico , Desoxirribonucleasa I/uso terapéutico , Expectorantes/uso terapéutico , Adolescente , Niño , Preescolar , Desoxirribonucleasa I/efectos adversos , Expectorantes/efectos adversos , Volumen Espiratorio Forzado , Humanos , Lactante , Manitol/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como Asunto , Proteínas Recombinantes/efectos adversos , Proteínas Recombinantes/uso terapéutico , Solución Salina Hipertónica/uso terapéutico , Capacidad VitalRESUMEN
OBJECTIF: Mettre en valeur les recommandations des lignes directrices de 2021 de la Société canadienne de thoracologie (SCT) pour les adultes et les enfants de 12 ans et plus, et aborder les controverses entourant leur actualisation. SOURCES DE L'INFORMATION: Les lignes directrices de 2021 de la SCT sur l'asthme. MESSAGE PRINCIPAL: L'asthme est un problème souvent rencontré en soins primaires. Un mauvais contrôle des symptômes et les exacerbations contribuent considérablement à la morbidité. Au cours des dernières années, les lignes directrices de pratique clinique ont eu tendance à préconiser un traitement plus intense de l'asthme très léger et léger dans le but d'optimiser la maîtrise des symptômes et de réduire les exacerbations. Il faut tenir compte du risque d'exacerbations, de l'ampleur des symptômes d'asthme, des degrés d'adhésion et du coût du traitement dans le choix d'une thérapie pour les patients atteints d'un asthme très léger et léger. CONCLUSION: Cet article a pour but de passer brièvement en revue les données probantes et les justifications qui sous-tendent les options de traitement dans les lignes directrices de la SCT, pour aider les médecins à prendre des décisions centrées sur le patient.
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BACKGROUND: Medical schools rarely offer exposure to clinical dermatology in the first-year curriculum. OBJECTIVE: We describe and report student satisfaction results of three novel teaching methods for integrating basic dermatology concepts into gross anatomy laboratory. METHODS: During the first year of the intervention, 180 students attended an hour-long anatomy laboratory session during which skin lesions were examined. One attending and three resident dermatologists spent time at all tables of students, then circulated to answer questions. During the second year, 189 students participated in the same teaching session preceded by a 30-minute in-class lecture. During the third year, 172 students were given the option to view a supplemental online video module before or after the teaching session. Each year following the teaching session, students were sent an optional online survey regarding the impact of the teaching session on their understanding of skin lesions and their cadaver experience. RESULTS: Overall, students felt the intervention helped them develop a better understanding and appreciation for dermatology. Preceding the laboratory session with a lecture or educational video yielded higher satisfaction scores. CONCLUSIONS: This brief teaching intervention illustrates an approach to introducing dermatologic entities within the foundational science curriculum of the first year of medical school.
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Anatomía/educación , Curriculum , Dermatología/educación , Educación de Pregrado en Medicina/métodos , Satisfacción Personal , Humanos , Estudiantes de MedicinaRESUMEN
The forkhead box (FOX) transcription factors have roles in development, carcinogenesis, metabolism, and immunity. In humans FOXP1 mutations have been associated with language and speech defects, intellectual disability, autism spectrum disorder, facial dysmorphisms, and congenital anomalies of the kidney and urinary tract. In mice, Foxp1 plays critical roles in development of the spinal motor neurons, lymphocytes, cardiomyocytes, foregut, and skeleton. We hypothesized therefore that mutations of FOXP1 affect additional tissues in some humans. Supporting this hypothesis, we describe two individuals with novel variants of FOXP1 (NM_032682.5:c.975-2A>C and NM_032682.5:c.1574G>A) and additional features. One had a lung disease resembling neuroendocrine cell hyperplasia of infancy (NEHI), and the second had a skeletal disorder with undertubulation of the long bones and relapsing-remitting fevers associated with flushing and edema. Although attribution of these traits to mutation of FOXP1 requires ascertainment of additional patients, we hypothesize that the variable expression of these additional features might arise by means of stochastic developmental variation.
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Trastorno del Espectro Autista/genética , Factores de Transcripción Forkhead/genética , Discapacidad Intelectual/genética , Trastornos del Lenguaje/genética , Enfermedades Pulmonares/genética , Proteínas Represoras/genética , Secuencia de Aminoácidos , Trastorno del Espectro Autista/diagnóstico por imagen , Femenino , Haploinsuficiencia , Humanos , Recién Nacido , Discapacidad Intelectual/diagnóstico por imagen , Trastornos del Lenguaje/diagnóstico por imagen , Pulmón/diagnóstico por imagen , Enfermedades Pulmonares/diagnóstico , Masculino , Modelos Moleculares , Mutación , Fenotipo , Dominios Proteicos , Alineación de Secuencia , Secuenciación del ExomaRESUMEN
BACKGROUND/PURPOSE: Sufficient bony support is essential to ensure the success of dental implant osseointegration. However, the reconstruction of vertical ridge deficiencies is still a major challenge for dental implants. This study introduced a novel treatment strategy by infusing poly(D,L-lactide-co-glycolide) (PLGA) microspheres encapsulating bone morphogenetic protein-2 (BMP-2) within a gelatin/hydroxyapatite/ß-tricalcium phosphate (gelatin/HA/ß-TCP) cryogel composite to facilitate supra-alveolar ridge augmentation. METHODS: The gelatin scaffold was crosslinked using cryogel technique, and HA/ß-TCP particles were mechanically entrapped to form the gelatin/HA/ß-TCP composite. Co-axial electrohydrodynamic atomization technology was used to fabricate PLGA microspheres encapsulating BMP-2. The composites of gelatin/HA/ß-TCP alone, with infusion of BMP-2 solution (BMPi) or microspheres (BMPm), were fixed on rat mandibles using a titanium mini-implant for 4 weeks, and the therapeutic efficiency was evaluated by micro-computed tomography, bone fluorochrome, and histology. RESULTS: The gelatin/HA/ß-TCP composite was homogenously porous, and BMP-2 was sustained release from the microspheres without initial burst release. Ridge augmentation was noted in all specimens treated with the gelatin/HA/ß-TCP composite, and greater bone deposition ratio were noted in Groups BMPi and BMPm. Compared with Group BMPi, specimens in Group BMPm showed significantly greater early osteogenesis and evident osseointegration in the supra-alveolar level. CONCLUSION: BMP-2 loaded PLGA microspheres effectively promoted osteogenic potential of the gelatin/HA/ß-TCP composite and facilitated supra-alveolar ridge augmentation in vivo.
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Aumento de la Cresta Alveolar/métodos , Proteína Morfogenética Ósea 2/administración & dosificación , Criogeles/química , Implantes Dentales , Ingeniería de Tejidos/métodos , Andamios del Tejido , Aumento de la Cresta Alveolar/instrumentación , Animales , Regeneración Ósea , Gelatina/administración & dosificación , Hidroxiapatitas/química , Ácido Láctico/química , Masculino , Mandíbula/cirugía , Microesferas , Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Ratas , Ratas Sprague-Dawley , Microtomografía por Rayos XRESUMEN
OBJECTIVES: The present study sought to determine the long-term growth consequences after a pulmonary exacerbation in children with cystic fibrosis (CF). METHODS: Retrospective cohort study of pediatric patients with CF with a hospital admission for a pulmonary exacerbation. Logistic regression used to determine risk factors for failure to recover baseline body mass index (BMI) percentile. RESULTS: Of 72 patients, 43% failed to recover their baseline BMI percentile 12 months after discharge and these patients also had a lower forced expiratory volume in 1 second at follow-up. A greater decrease in weight percentile from baseline to admission was the only risk factor identified (odds ratio 0.83, Pâ=â0.0015). CONCLUSIONS: Greater decrease in weight percentile from baseline to admission predicts failure to recover BMI percentile 1 year after a pulmonary exacerbation. Children with CF with poor growth preceding a pulmonary exacerbation continue to be at risk for long-term nutritional failure despite treatment for pulmonary exacerbation.
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BACKGROUND: Dornase alfa is currently used as a mucolytic to treat pulmonary disease (the major cause of morbidity and mortality) in cystic fibrosis. It reduces mucus viscosity in the lungs, promoting improved clearance of secretions. This is an update of a previously published review. OBJECTIVES: To determine whether the use of dornase alfa in cystic fibrosis is associated with improved mortality and morbidity compared to placebo or other medications that improve airway clearance, and to identify any adverse events associated with its use. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises references identified from comprehensive electronic database searches, handsearching relevant journals and abstracts from conferences. Date of the most recent search of the Group's Cystic Fibrosis Register: 30 November 2015.Clinicaltrials.gov was also searched to identify unpublished or ongoing trials. Date of most recent search: 28 November 2015. SELECTION CRITERIA: All randomised and quasi-randomised controlled trials comparing dornase alfa to placebo, standard therapy or other medications that improve airway clearance. DATA COLLECTION AND ANALYSIS: Authors independently assessed trials against the inclusion criteria; two authors carried out analysis of methodological quality and data extraction. MAIN RESULTS: The searches identified 54 trials, of which 19 (including a total of 2565 participants) met our inclusion criteria. Three additional papers examined the healthcare cost from one of the clinical trials. Fifteen trials compared dornase alfa to placebo or no dornase alfa treatment (2447 participants); two compared daily dornase to hypertonic saline (32 participants); one compared daily dornase alfa with hypertonic saline and alternate day dornase alfa (48 participants); one compared dornase alfa to mannitol and the combination of both drugs (38 participants). Trial duration varied from six days to three years.Compared to placebo, forced expiratory volume at one second improved in the intervention groups, with significant differences at one, three, six months and two years. There was also a significant improvement in lung clearance index at one month. There was a decrease in pulmonary exacerbations compared to placebo in trials of longer duration. The quality of the evidence from placebo-controlled trials was moderate to high for outcomes of lung function and pulmonary exacerbations. Limited, low quality evidence was available for changes in quality of life from baseline. One trial that examined the cost of care, including the cost of dornase alfa, found that the cost savings from dornase alfa offset 18% to 38% of the medication costs.The results for trials comparing dornase alfa to other medications that improve airway clearance (hypertonic saline or mannitol) were mixed, with one trial showing a greater improvement in forced expiratory volume at one second for dornase alfa compared to hypertonic saline, and three trials finding no difference between medications. In the only trial to assess the combination of dornase alfa with another medication compared to dornase alone, there was no benefit seen with the combination of dornase alfa and mannitol. Evidence of dornase alfa compared to other medications was limited and the open-label design of the trials may have induced bias, therefore the quality of the evidence was judged to be low.Dornase alfa did not cause significantly more adverse effects, except voice alteration and rash. AUTHORS' CONCLUSIONS: There is evidence to show that, compared with placebo, therapy with dornase alfa improves lung function in people with cystic fibrosis in trials lasting one month to two years. There was a decrease in pulmonary exacerbations in trials of six months or longer. Voice alteration and rash appear to be the only adverse events reported with increased frequency in randomised controlled trials. There is not enough evidence to firmly conclude if dornase alfa is superior to hyperosmolar agents in improving lung function.