RESUMEN
Individuals with cystic fibrosis (CF) develop complications of the gastrointestinal tract influenced by genetic variants outside of CFTR. Cystic fibrosis-related diabetes (CFRD) is a distinct form of diabetes with a variable age of onset that occurs frequently in individuals with CF, while meconium ileus (MI) is a severe neonatal intestinal obstruction affecting â¼20% of newborns with CF. CFRD and MI are slightly correlated traits with previous evidence of overlap in their genetic architectures. To better understand the genetic commonality between CFRD and MI, we used whole-genome-sequencing data from the CF Genome Project to perform genome-wide association. These analyses revealed variants at 11 loci (6 not previously identified) that associated with MI and at 12 loci (5 not previously identified) that associated with CFRD. Of these, variants at SLC26A9, CEBPB, and PRSS1 associated with both traits; variants at SLC26A9 and CEBPB increased risk for both traits, while variants at PRSS1, the higher-risk alleles for CFRD, conferred lower risk for MI. Furthermore, common and rare variants within the SLC26A9 locus associated with MI only or CFRD only. As expected, different loci modify risk of CFRD and MI; however, a subset exhibit pleiotropic effects indicating etiologic and mechanistic overlap between these two otherwise distinct complications of CF.
Asunto(s)
Fibrosis Quística , Diabetes Mellitus , Enfermedades del Recién Nacido , Obstrucción Intestinal , Fibrosis Quística/complicaciones , Fibrosis Quística/genética , Regulador de Conductancia de Transmembrana de Fibrosis Quística/genética , Diabetes Mellitus/genética , Estudio de Asociación del Genoma Completo , Humanos , Recién Nacido , Obstrucción Intestinal/complicaciones , Obstrucción Intestinal/genéticaRESUMEN
Rationale: Lung disease is the major cause of morbidity and mortality in persons with cystic fibrosis (pwCF). Variability in CF lung disease has substantial non-CFTR (CF transmembrane conductance regulator) genetic influence. Identification of genetic modifiers has prognostic and therapeutic importance. Objectives: Identify genetic modifier loci and genes/pathways associated with pulmonary disease severity. Methods: Whole-genome sequencing data on 4,248 unique pwCF with pancreatic insufficiency and lung function measures were combined with imputed genotypes from an additional 3,592 patients with pancreatic insufficiency from the United States, Canada, and France. This report describes association of approximately 15.9 million SNPs using the quantitative Kulich normal residual mortality-adjusted (KNoRMA) lung disease phenotype in 7,840 pwCF using premodulator lung function data. Measurements and Main Results: Testing included common and rare SNPs, transcriptome-wide association, gene-level, and pathway analyses. Pathway analyses identified novel associations with genes that have key roles in organ development, and we hypothesize that these genes may relate to dysanapsis and/or variability in lung repair. Results confirmed and extended previous genome-wide association study findings. These whole-genome sequencing data provide finely mapped genetic information to support mechanistic studies. No novel primary associations with common single variants or rare variants were found. Multilocus effects at chr5p13 (SLC9A3/CEP72) and chr11p13 (EHF/APIP) were identified. Variant effect size estimates at associated loci were consistently ordered across the cohorts, indicating possible age or birth cohort effects. Conclusions: This premodulator genomic, transcriptomic, and pathway association study of 7,840 pwCF will facilitate mechanistic and postmodulator genetic studies and the development of novel therapeutics for CF lung disease.
Asunto(s)
Fibrosis Quística , Humanos , Fibrosis Quística/genética , Estudio de Asociación del Genoma Completo/métodos , Regulador de Conductancia de Transmembrana de Fibrosis Quística/genética , Gravedad del Paciente , Pulmón , Proteínas Asociadas a Microtúbulos/genéticaRESUMEN
OBJECTIVE: The aim of this study was to assess the impact race and language have on emergency department (ED) triage scores while accounting for illness severity. We hypothesized that non-White and non-English-speaking patients were assigned lower-acuity triage scores compared with White and English-speaking patients, respectively. METHODS: We used a chart review-based retrospective cohort study design, examining patients aged 0 to 17 years at our pediatric ED from July 2015 through June 2016. Illness severity was measured using a truncated Modified Pediatric Early Warning Score calculated from patient vital signs. We used univariate and multivariate multinomial logistic regression to assess the association between race and language with Emergency Severity Index scores. RESULTS: Our final data set consisted of 10,815 visits from 8928 patients. Non-Hispanic (NH) White patients accounted for 34.6% of patients. In the adjusted analyses, non-White patients had significantly reduced odds of receiving a score of 2 (emergency) (odds ratio [OR], 0.4; 95% confidence interval [CI], 0.33-0.49) or 3 (urgent) (OR, 0.5; 95% CI, 0.45-0.56) and significantly higher odds of receiving a score of 5 (minor) (OR, 1.34; 95% CI, 1.07-1.69) versus a score of 4 (nonurgent). We did not find a consistent disparity in Emergency Severity Index scores when comparing English- and non-English-speaking patients. CONCLUSIONS: We confirm that non-White patients receive lower triage scores than White patients. A more robust tool is required to account for illness severity and will be critical to understanding whether the relationship we describe reflects bias within the triage system or differences in ED utilization by racial groups.
Asunto(s)
Servicio de Urgencia en Hospital , Disparidades en Atención de Salud , Lenguaje , Triaje , Niño , Humanos , Estudios Retrospectivos , Disparidades en Atención de Salud/etnología , Recién Nacido , Lactante , Preescolar , Adolescente , Grupos RacialesRESUMEN
BACKGROUND: While Pseudomonas aeruginosa (Pa) eradication regimens have contributed to a decline in Pa prevalence in people with cystic fibrosis (CF), this antibiotic exposure might increase the risk of acquisition of drug-resistant organisms. This study evaluated the association between antipseudomonal antibiotic exposure intensity and acquisition risk of drug-resistant organisms among children with CF and new Pa infection. METHODS: We utilized data from the Early Pseudomonas Infection Control Clinical Trial (EPIC CT), a randomized controlled trial comparing Pa eradication strategies in children with CF and new Pa. The exposure was the number of weeks of oral or inhaled antipseudomonal antibiotics or ever versus never treatment with intravenous antipseudomonal antibiotics during the 18 months of EPIC CT participation. Primary outcomes were risks of acquisition of several respiratory organisms during 5 years of follow-up after EPIC CT estimated using Cox proportional hazards models separately for each specific organism. RESULTS: Among 249 participants, there was no increased acquisition risk of any organism associated with greater inhaled antibiotic exposure. With each additional week of oral antibiotics, there was an increased hazard of Achromobacter xylosoxidans acquisition (HR, 1.24; 95% CI: 1.02-1.50; Pâ =â .03). Treatment with intravenous antibiotics was associated with an increased hazard of acquisition of multidrug-resistant Pa (HR, 2.47; 95% CI: 1.28-4.78; Pâ =â .01) and MRSA (HR, 1.57; 95% CI: 1.03-2.40; Pâ =â .04). CONCLUSIONS: Results from this study illustrate the importance of making careful antibiotic choices to balance the benefits of antibiotics in people with CF while minimizing risk of acquisition of drug-resistant organisms.
Asunto(s)
Fibrosis Quística , Infecciones por Pseudomonas , Administración por Inhalación , Antibacterianos/efectos adversos , Niño , Fibrosis Quística/complicaciones , Fibrosis Quística/tratamiento farmacológico , Humanos , Infecciones por Pseudomonas/tratamiento farmacológico , Infecciones por Pseudomonas/epidemiología , Pseudomonas aeruginosaRESUMEN
BACKGROUND: Pulmonary exacerbations (PEx) in people with cystic fibrosis (PwCF) are associated with significant morbidity. While standard PEx treatment for PwCF with Pseudomonas aeruginosa infection includes two IV antipseudomonal antibiotics, little evidence exists to recommend this approach. This study aimed to compare clinical outcomes of single versus double antipseudomonal antibiotic use for PEx treatment. METHODS: Retrospective cohort study using the linked CF Foundation Patient Registry-Pediatric Health Information System dataset. PwCF were included if hospitalized between 2007 and 2018 and 6-21 years of age. Regression modeling accounting for repeated measures was used to compare lung function outcomes between single versus double IV antipseudomonal antibiotic regimens using propensity-score weighting to adjust for relevant confounding factors. RESULTS: Among 10,660 PwCF in the dataset, we analyzed 2,578 PEx from 1,080 PwCF, of which 455 and 2,123 PEx were treated with 1 versus 2 IV antipseudomonal antibiotics, respectively. We identified no significant differences between PEx treated with 1 versus 2 IV antipseudomonal antibiotics either in change between pre- and post-PEx percent predicted forced expiratory volume in one second (ppFEV1) (-0.84%, [95% CI -2.25, 0.56]; P = 0.24), odds of returning to ≥90% of baseline ppFEV1 within 3 months following PEx (Odds Ratio 0.83, [95% CI 0.61, 1.13]; P = 0.24) or time to next PEx requiring IV antibiotics (Hazard Ratio 1.04, [95% CI 0.87, 1.24]; P = 0.69). CONCLUSIONS: Use of 2 IV antipseudomonal antibiotics for PEx treatment in young PwCF was not associated with greater improvements in measured respiratory and clinical outcomes compared to treatment with 1 IV antipseudomonal antibiotic.
Asunto(s)
Fibrosis Quística , Infecciones por Pseudomonas , Antibacterianos/uso terapéutico , Niño , Fibrosis Quística/complicaciones , Fibrosis Quística/tratamiento farmacológico , Volumen Espiratorio Forzado , Humanos , Infecciones por Pseudomonas/tratamiento farmacológico , Estudios RetrospectivosRESUMEN
BACKGROUND/OBJECTIVE: Studies have identified dermatologic conditions and relevant skin-related behaviors that distinctly or disproportionately impact sexual and gender minority (SGM) adults compared with their cisgender/heterosexual counterparts, but whether these observations apply to SGM adolescents remains unknown. We aimed to describe the nature and frequency of skin conditions in SGM youth relative to their cisgender/heterosexual peers and explore adolescents' attitudes toward their skin health and accessing dermatologic care. METHODS: SGM and cisgender/heterosexual youth aged 13-21 years seen at Seattle Children's Hospital Adolescent Medicine and Gender clinics from June to December 2019 were invited to participate in this cross-sectional survey study, with subsequent statistical analysis. RESULTS: One-hundred and eighteen subjects were included in the study. Sexual orientation did not affect how participants personally felt about and cared for their skin, though gender identity did influence this relationship. (P = .012) Both sexual and gender minority youth demonstrated a preference for a dermatologist who identified as SGM and would be more likely to actively seek care from these providers. (P < .001) There was no difference in the reported prevalence of most dermatologic conditions among groups based on sexual orientation or gender identity. CONCLUSION: Dermatologists should inquire with adolescent and young adult patients how their sexual orientation and gender identities influence how they view their skin, in an effort to guide counseling and demonstrate holistic support for adolescents. Therapeutic alliances with SGM youth may be strengthened by providers who openly identify as SGM.
Asunto(s)
Identidad de Género , Minorías Sexuales y de Género , Adolescente , Niño , Estudios Transversales , Femenino , Heterosexualidad , Humanos , Masculino , Conducta Sexual , Adulto JovenRESUMEN
BACKGROUND: During antiretroviral treatment (ART) with plasma HIV RNA below the limit of quantification, HIV RNA can be detected in genital or rectal secretions, termed discordant shedding (DS). We hypothesized that proliferating cells produce virions without HIV replication. METHODS: ART-naive Peruvians initiating ART were observed for DS over 2 years. HIV env and pol genomes were amplified from DS. Antiretrovirals and cytokines/chemokines concentrations were compared at DS and control time points. RESULTS: Eighty-two participants had ART suppression. DS was detected in 24/82 (29%) participants: 13/253 (5%) cervicovaginal lavages, 20/322 (6%) seminal plasmas, and 6/85 (7%) rectal secretions. HIV RNA in DS specimens was near the limit of quantification and not reproducible. HIV DNA was detected in 6/13 (46%) DS cervicovaginal lavages at low levels. Following DNase treatment, 5/39 DS specimens yielded HIV sequences, all without increased genetic distances. Women with and without DS had similar plasma antiretroviral levels and DS in 1 woman was associated with inflammation. CONCLUSIONS: HIV RNA and DNA sequences and therapeutic antiretroviral plasma levels did not support HIV replication as the cause of DS from the genital tract. Rather, our findings infer that HIV RNA is shed due to proliferation of infected cells with virion production.
Asunto(s)
Fármacos Anti-VIH/uso terapéutico , Secreciones Corporales/virología , ADN Viral/análisis , Infecciones por VIH/tratamiento farmacológico , VIH-1/fisiología , ARN Viral/análisis , Esparcimiento de Virus , Adulto , Fármacos Anti-VIH/sangre , Cuello del Útero/virología , Citocinas/sangre , Femenino , Genes env , Genes pol , VIH-1/genética , Humanos , Masculino , Estudios Prospectivos , ARN Viral/sangre , Recto/virología , Semen/virología , Análisis de Secuencia de ADN , Análisis de Secuencia de ARN , Irrigación Terapéutica , Vagina/virología , Carga Viral , Replicación Viral/efectos de los fármacos , Adulto JovenRESUMEN
AIM: We examined the impact of introducing high-flow nasal oxygen therapy (HFNT) on children under five with post-extubation respiratory failure in a paediatric intensive care unit (PICU) in Peru. METHODS: This quasi-experimental study compared clinical outcomes before and after initial HFNT deployment in the PICU at Instituto Nacional de Salud del Niño in Lima in June 2016. We compared three groups: 29 received post-extubation HFNT and 17 received continuous positive airway pressure (CPAP) from 2016-17 and 12 historical controls received CPAP from 2012-16. The primary outcome was the need for mechanical ventilation. Adjusted hazard ratios (aHR) and 95% confidence intervals (95% CI) were calculated via survival analysis. RESULTS: High-flow nasal oxygen therapy and CPAP did not alter the need for mechanical ventilation after extubation (aHR 0.47, 95% CI 0.15-1.48 and 0.96, 95% CI 0.35-2.62, respectively) but did reduce the risk of reintubation (aHR 0.18, 95% CI 0.06-0.57 and 0.14, 95% CI 0.03-0.72, respectively). PICU length of stay was 11, 18 and 37 days for CPAP, HFNT and historical CPAP and mortality was 12%, 7% and 27%, respectively. There was no effect on the duration of sedative infusions. CONCLUSION: High-flow nasal oxygen therapy provided effective support for some children, but larger studies in resource-constrained settings are needed.
Asunto(s)
Extubación Traqueal , Terapia por Inhalación de Oxígeno , Niño , Humanos , Unidades de Cuidado Intensivo Pediátrico , Intubación Intratraqueal , PerúRESUMEN
BACKGROUND: Epidural analgesia is considered optimal for postoperative pain management after major abdominal surgery. The potential to decrease anesthetic and opioid exposure is particularly desirable for infants, given their vulnerability to respiratory depression and concern for anesthetic neurotoxicity. We reviewed our experience with infants undergoing major abdominal surgery to determine if epidural catheter use decreased anesthetic and opioid exposure and improved postoperative analgesia. METHODS: This retrospective cohort study included infants (<12 months) who underwent exploratory laparotomy, ureteral reimplantation, or bladder exstrophy repair between November 2011 and November 2014. Primary outcomes of anesthetic exposure (mean endtidal sevoflurane) and intraoperative opioid administration were compared between infants who received epidural catheters and those who did not. Secondary outcomes included postoperative pain and sedation scores and morphine equivalents administered 0-24 and 24-48 hours after surgery. RESULTS: Of 158 eligible infants, 82 were included and 47 received epidurals. Patients with epidurals underwent bladder exstrophy repair (N = 9), ureteral reimplantation (N = 8), and exploratory laparotomy (N = 30). Infants with epidurals received less intraoperative fentanyl (2.6 mcg/kg (0,4.5) vs 3.3 mcg/kg (2.4,5.8), P = 0.019) and morphine (6% (3/47) vs 26% (9/35), P = 0.014) in univariate analysis. After controlling for age and emergency surgery, differences in long-acting opioid administration persisted, with significantly less morphine given in the epidural group (OR 0.181; 95% CI 0.035-0.925; P = 0.040). Mean endtidal sevoflurane concentrations were similar between groups. There was no significant difference in postoperative median morphine equivalents. CONCLUSION: Placement of epidural catheters in infants undergoing major abdominal surgery is associated with decreased long-acting opioid requirements intraoperatively. Epidural placement does not preclude opioid exposure however, as opioids may be administered for indications other than nociceptive pain in the difficult-to-assess postoperative infant. Further prospective studies are warranted to better quantify the effect of epidural analgesia on intraoperative anesthetic exposure in infants.
Asunto(s)
Analgesia Epidural , Analgesia/métodos , Analgésicos Opioides/administración & dosificación , Anestésicos/administración & dosificación , Dolor Postoperatorio/tratamiento farmacológico , Humanos , Lactante , Recién Nacido , Estudios RetrospectivosRESUMEN
INTRODUCTION: Although two billion people now have access to clean water, many hospitals in low- and middle-income countries (LMICs) do not. Lack of water availability at hospitals hinders safe surgical care. We aimed to review the surgical capacity literature and document the availability of water at health facilities and develop a predictive model of water availability at health facilities globally to inform targeted capacity improvements. METHODS: Using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a systematic search for surgical capacity assessments in LMICs in MEDLINE, PubMed, and World Health Organization Global Health Library was performed. Data regarding water availability were extracted. Data from these assessments and national indicator data from the World Bank (e.g., gross domestic product, total health expenditure, and percent of population with improved access to water) were used to create a predictive model for water availability in LMICs globally. RESULTS: Of the 72 records identified, 19 reported water availability representing 430 hospitals. A total of 66% of hospitals assessed had water availability (283 of 430 hospitals). Using these data, estimated percent of water availability in LMICs more broadly ranged from under 20% (Liberia) to over 90% (Bangladesh, Ghana). CONCLUSIONS: Less than two-thirds of hospitals providing surgical care in 19 LMICs had a reliable water source. Governments and nongovernmental organizations should increase efforts to improve water infrastructure at hospitals, which might aid in the provision of safe essential surgical care. Future research is needed to measure the effect of water availability on surgical care and patient outcomes.
Asunto(s)
Países en Desarrollo/estadística & datos numéricos , Cirugía General , Hospitales/estadística & datos numéricos , Abastecimiento de AguaRESUMEN
BACKGROUND: In 2010, the World Health Organization shifted its malaria guidelines from recommending the empiric treatment of all febrile children to treating only those with laboratory-confirmed malaria. This study evaluated the frequency and predictors of malaria over-treatment among febrile malaria-negative children in Kenya. METHODS: Between 2012 and 2013, 1,362 children presenting consecutively with temperature ≥37.5°C to Kisii and Homa Bay hospitals were enrolled in a cross-sectional study evaluating causes of fever. Children were screened for malaria using smear microscopy and rapid diagnostic tests and managed according to standard of care at the hospitals. The frequency of anti-malarial prescriptions among children with laboratory-confirmed malaria negative children (malaria over-treatment) was determined; and clinical and demographic correlates of overtreatment evaluated using logistic regression. Because of differences in malaria endemicity, analyses were stratified and compared by site. RESULTS: Among 1,362 children enrolled, 46 (7%) of 685 children in Kisii, and 310 (45.8%) of 677 in Homa Bay had laboratory-confirmed malaria; p < 0.001. Among malaria-negative children; 210 (57.2%) in Homa Bay and 45 (7.0%) in Kisii received anti-malarials; p < 0.001. Predictors of over-treatment in Homa Bay included ≥ one integrated management of childhood illness (IMCI) danger sign (aOR = 8.47; 95% CI: 4.81-14.89), fever lasting ≥ seven days (aOR = 4.94; 95% CI: 1.90-12.86), and fever ≥39°C (aOR = 3.07; 95% CI: 1.58-5.96). In Kisii, only fever ≥39°C predicted over-treatment (aOR = 2.13; 95% CI: 1.02-4.45). CONCLUSIONS: Malaria over-treatment was common, particularly in Homa Bay, where the prevalence of malaria was extremely high. Severe illness and high or prolonged fever were associated with overtreatment. Overtreatment may result in failure to treat other serious causes of fever, drug resistance, and unnecessarily treatment costs.
Asunto(s)
Antimaláricos/uso terapéutico , Malaria/tratamiento farmacológico , Malaria/epidemiología , Plasmodium falciparum/efectos de los fármacos , Adolescente , Antimaláricos/farmacología , Niño , Preescolar , Estudios Transversales , Femenino , Fiebre/epidemiología , Fiebre/parasitología , Humanos , Lactante , Recién Nacido , Kenia/epidemiología , Malaria/parasitología , MasculinoRESUMEN
OBJECTIVE: Seizure frequency represents a commonly assessed epilepsy status, but in the context of the growing trend toward patient-centered care, we examined the adequacy of seizure frequency as a measure of epilepsy status as perceived by the patient. METHODS: Between 2006 and 2008, we assessed seizure frequency, mood, and preference-based health-related quality of life (HRQOL) measured with the visual analog scale metric in 182 adult patients sampled consecutively. Using nonparametric tests and Monte Carlo computer simulations, we analyzed the relationship between preference-based HRQOL and seizure frequency, and using regression analyses, we tested for significant predictors of preference-based HRQOL. RESULTS: Only patients who had been seizure-free for >1 year had significantly higher preference-based HRQOL (p < 0.0001) than those who experienced any recurrent seizure, regardless of their seizure frequency. Among patients with recurrent seizures, preference-based HRQOL and seizure frequency were not monotonically, linearly related. For patients with similar seizure frequency, preference-based HRQOL varied substantially with large overlaps in preference-based HRQOL across different seizure frequency categories. The Monte Carlo simulation found that seizure frequency was a poor predictor of preference-based HRQOL about one third of the time. The presence of depressive symptoms was an independent predictor of preference-based HRQOL measure, accounting for 33.5% of the variation in scores between patients. SIGNIFICANCE: Our findings highlight the importance of attaining complete seizure freedom and the substantial variation in preference-based HRQOL among patients with similar seizure frequencies. To improve assessment of patient-centered outcomes in epilepsy, we encourage adding direct measurement of preference-based HRQOL into clinical care.
Asunto(s)
Epilepsia/diagnóstico , Epilepsia/psicología , Evaluación del Resultado de la Atención al Paciente , Calidad de Vida/psicología , Adulto , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Estudios Retrospectivos , Convulsiones/diagnóstico , Convulsiones/psicología , Factores de TiempoRESUMEN
Rationale: Pulmonary exacerbation (PEx) events contribute to lung function decline in people with cystic fibrosis (CF). CF Foundation PEx guidelines note that a short course of systemic corticosteroids may offer benefit without contributing to long-term adverse effects. However, insufficient evidence exists to recommend systemic corticosteroids for PEx treatment. Objectives: To determine if systemic corticosteroids for the treatment of in-hospital pediatric PEx are associated with improved clinical outcomes compared with treatment without systemic corticosteroids. Methods: We conducted a retrospective cohort study using the CF Foundation Patient Registry-Pediatric Health Information System linked database. People with CF were included if hospitalized for a PEx between 2006 and 2018 and were 6-21 years of age. Time to next PEx was assessed by Cox proportional hazards regression. Lung function outcomes were assessed by linear mixed-effect modeling and generalized estimating equations. To address confounding by indication, inverse probability treatment weighting was used. Results: A total of 3,471 people with CF contributed 9,787 PEx for analysis. Systemic corticosteroids were used in 15% of all PEx. In our primary analysis, systemic corticosteroids were not associated with better pre- to post-PEx percent predicted forced expiratory volume in 1 second responses (mean difference, -0.36; 95% confidence interval [CI], -1.14, 0.42; P = 0.4) or a higher odds of returning to lung function baseline (odds ratio, 0.97; 95% CI, 0.84-1.12; P = 0.7) but were associated with a reduced chance of future PEx requiring intravenous antibiotics (hazard ratio, 0.91; 95% CI, 0.85-0.96; P = 0.002). When restricting the analysis to one PEx per person, lung function outcomes remained no different among PEx treated with or without systemic corticosteroids, but, in contrast to our primary analysis, the use of systemic corticosteroids was no longer associated with a reduced chance of having a future PEx requiring intravenous antibiotics (hazard ratio, 0.96; 95% CI, 0.86, 1.07; P = 0.42). Conclusions: Systemic corticosteroid treatment for in-hospital pediatric PEx was not associated with improved lung function outcomes. Prospective trials are needed to better evaluate the risks and benefits of systemic corticosteroid use for PEx treatment in children with CF.
Asunto(s)
Fibrosis Quística , Humanos , Niño , Fibrosis Quística/complicaciones , Fibrosis Quística/tratamiento farmacológico , Estudios Prospectivos , Estudios Retrospectivos , Progresión de la Enfermedad , Volumen Espiratorio Forzado , Corticoesteroides/uso terapéutico , Antibacterianos/uso terapéuticoRESUMEN
INTRODUCTION: Voluntary medical male circumcision (VMMC) for HIV prevention began in Nyanza Region, Kenya in 2008. By 2014, approximately 800,000 VMMCs had been conducted, and 84.9% were among males aged 15-24 years. We evaluated the impact of interpersonal communication (IPC) and dedicated service outlets (DSO) on VMMC uptake among men aged 25-39 years in Nyanza Region. MATERIALS AND METHODS: We conducted a cluster randomized controlled trial in 45 administrative Locations (clusters) in Nyanza Region between May 2014 and June 2016 among uncircumcised men aged 25-34 years. In arm one, an IPC toolkit was used to address barriers to VMMC. In the second arm, men were referred to DSO that were modified to address their preferences. Arm three combined the IPC and DSO arms, and arm four was standard of care (SOC). Randomization was done at Location level (11-12 per arm). The primary outcome was the proportion of enrolled men who received VMMC within three months. Generalized estimating equations were used to evaluate the effect of interventions on the outcome. RESULTS: At baseline, 9,238 households with men aged 25-39 years were enumerated, 9,679 men were assessed, and 2,792 (28.8%) were eligible. For enrollment, 577 enrolled in the IPC arm, 825 in DSO, 723 in combined IPC + DSO, and 667 in SOC. VMMC uptake among men in the SOC arm was 3.2%. In IPC, DSO, and combined IPC + DSO arms, uptake was 3.3%, 4.5%, and 4.4%, respectively. The adjusted odds ratio (aOR) of VMMC uptake in the study arms compared to SOC were IPC aOR = 1.03; 95% CI: 0.50-2.13, DSO aOR = 1.31; 95% CI: 0.67-2.57, and IPC + DSO combined aOR = 1.31, 95% CI: 0.65-2.67. DISCUSSION: Using these interventions among men aged 25-39 years did not significantly impact VMMC uptake. These findings suggest that alternative demand creation strategies for VMMC services are needed to reach men aged 25-39 years. TRIAL REGISTRATION: clinicaltrials.gov identifier: NCT02497989.
Asunto(s)
Fenómenos Bioquímicos , Circuncisión Masculina , Infecciones por VIH , Humanos , Masculino , Kenia , Comunicación , Infecciones por VIH/prevención & controlRESUMEN
BACKGROUND: Pseudomonas aeruginosa (Pa) infection in cystic fibrosis (CF) is characterized in stages: never (prior to first positive culture) to incident (first positive culture) to chronic. The association of Pa infection stage with lung function trajectory is poorly understood and the impact of age on this association has not been examined. We hypothesized that FEV1 decline would be slowest prior to Pa infection, intermediate after incident infection and greatest after chronic Pa infection. METHODS: Participants in a large US prospective cohort study diagnosed with CF prior to age 3 contributed data through the U.S. CF Patient Registry. Cubic spline linear mixed effects models were used to evaluate the longitudinal association of Pa stage (never, incident, chronic using 4 different definitions) with FEV1 adjusted for relevant covariates. Models contained interaction terms between age and Pa stage. RESULTS: 1,264 subjects born 1992-2006 provided a median 9.5 (IQR 0.25 to 15.75) years of follow up through 2017. 89% developed incident Pa; 39-58% developed chronic Pa depending on the definition. Compared to never Pa, incident Pa infection was associated with greater annual FEV1 decline and chronic Pa infection with the greatest FEV1 decline. The most rapid FEV1 decline and strongest association with Pa infection stage was seen in early adolescence (ages 12-15). CONCLUSIONS: Annual FEV1 decline worsens significantly with each Pa infection stage in children with CF. Our findings suggest that measures to prevent chronic infection, particularly during the high-risk period of early adolescence, could mitigate FEV1 decline and improve survival.
Asunto(s)
Fibrosis Quística , Infecciones por Pseudomonas , Adolescente , Humanos , Niño , Preescolar , Fibrosis Quística/complicaciones , Fibrosis Quística/diagnóstico , Fibrosis Quística/epidemiología , Infecciones por Pseudomonas/diagnóstico , Infecciones por Pseudomonas/epidemiología , Infecciones por Pseudomonas/complicaciones , Estudios Prospectivos , Pruebas de Función Respiratoria , Pseudomonas aeruginosa , PulmónRESUMEN
Rationale: Primary ciliary dyskinesia (PCD) is characterized by impaired mucociliary clearance, recurrent respiratory infections, progressive airway damage, and obstructive lung disease. Although the association of ciliary ultrastructure defect/genotype with the severity of airflow obstruction has been well characterized, their association with airway abnormalities on chest computed tomography (CT) has been minimally evaluated. Objectives: We sought to delineate the association of ciliary defect class/genotype with chest CT scores in children with PCD. Methods: Cross-sectional analysis of children with PCD (N = 146) enrolled in a prospective multicenter observational study, stratified by defect type: outer dynein arm (ODA), ODA/inner dynein arm (IDA), IDA/microtubular disorganization (MTD), and normal/near normal ultrastructure with associated genotypes. CTs were scored using the MERAGMA-PCD (Melbourne-Rotterdam Annotated Grid Morphometric Analysis for PCD), evaluating airway abnormalities in a hierarchical order: atelectasis, bronchiectasis, bronchial wall thickening, and mucus plugging/tree-in-bud opacities. The volume fraction of each component was expressed as the percentage of total lung volume. The percentage of disease was computed as the sum of all components. Regression analyses were used to describe the association between clinical predictors and CT scores. Results: Acceptable chest CTs were obtained in 141 children (71 male): 57 ODA, 20 ODA/IDA, 40 IDA/MTD, and 24 normal/near normal. The mean (standard deviation) age was 8.5 (4.6) years, forced expiratory volume in 1 second (FEV1) percent predicted was 82.4 (19.5), and %Disease was 4.6 (3.5). Children with IDA/MTD defects had a higher %Disease compared with children with ODA defects (2.71% higher [95% confidence interval (CI), 1.37-4.06; P < 0.001]), driven by higher %Mucus plugging (2.35% higher [1.43-3.26; P < 0.001]). Increasing age, lower body mass index, and lower FEV1 were associated with a higher %Disease (0.23%; 95% CI, 0.11-0.35; P < 0.001 and 0.03%; 95% CI, 0.01-0.04; P = 0.008 and 0.05%; 95% CI, 0.01-0.08; P = 0.011, respectively). Conclusions: Children with IDA/MTD defects had significantly greater airway disease on CT, primarily mucus plugging, compared with children with ODA defects.
Asunto(s)
Trastornos de la Motilidad Ciliar , Síndrome de Kartagener , Trastornos Respiratorios , Humanos , Niño , Trastornos de la Motilidad Ciliar/genética , Dineínas/genética , Estudios Prospectivos , Estudios Transversales , Genotipo , Cilios/ultraestructura , Síndrome de Kartagener/genéticaRESUMEN
BACKGROUND: Cystic fibrosis (CF)-specialized nutrition care strives to meet normal infant growth, but the relationship of dietitian assessments to weight outcomes is unknown. We characterize nutrition management for inadequate weight gain and assess association of dietitian assessments and center-level weight-for-age Z-scores (WAZ). METHODS: We used encounter data from 226 infants across 28 US CF Centers from the Baby Observational Nutritional study between January 2012 through December 2017. We identified dietitian assessments and consensus guideline-recommended responses to inadequate weight gain: calorie increases, pancreatic enzyme replacement therapy (PERT) increases, or shortened time to next visit. We compared center assessments by funnel plot and summarize median WAZ by center. RESULTS: Of 2,527 visits, 808 (32%) visits had identified inadequate weight gain, distributed in 216 infants. Assessments occurred in 1953 visits (77%), but varied widely between centers (range 17% - 98%). For inadequate weight gain, most and least common responses were calorie increase (64%) and PERT increase (21%). Funnel plot analysis identified 4 high-performers for frequent dietitian assessments (range 92% - 98%) and 4 under-performers (range 17% - 56%). High-performers treated inadequate weight gain more often with adequate calories (24/30, 80% v. 12/23, 52%) and closer follow up (104/164, 63% v. 60/120, 49%) compared to under-performers. Three of 4 high-performing sites met center nutrition goals for positive median WAZ at 2 years old unlike 3 under-performers (WAZHigh 0.33 v. WAZLow -0.15), despite similar patient characteristics. CONCLUSION: We characterized multicenter variation in dietitian assessments, identifying opportunities to improve care delivery to target early nutrition outcomes.
Asunto(s)
Fibrosis Quística/dietoterapia , Adhesión a Directriz , Evaluación Nutricional , Terapia Nutricional/métodos , Aumento de Peso , Preescolar , Femenino , Humanos , Lactante , Estudios Longitudinales , Masculino , Estado Nutricional , Estudios ProspectivosRESUMEN
Rationale: Antibiotic selection for pulmonary exacerbation (PEx) management in children with cystic fibrosis is typically guided by prior respiratory culture results. Although antipseudomonal antibiotics are often used in children with chronic Pseudomonas aeruginosa (Pa) airway infection, no data exist to guide antibiotic selection in children who are culture negative for Pa for ≥1 year. Objectives: To determine among children classified as 1, 2, or 3 years' Pa negative if PEx treatment with at least one oral and/or intravenous antipseudomonal antibiotic is associated with improved clinical outcomes compared with treatment with antibiotics not effective against Pa. Methods: A retrospective cohort study was conducted using the linked Cystic Fibrosis Foundation Patient Registry-Pediatric Health Information System database. We included children 6-21 years old hospitalized between 2008 and 2018 consistently culture negative for Pa 1 year before a study PEx. Children were classified as 1 or 2 years' Pa negative if their last Pa-positive culture occurred in the 13-24 months or 25-36 months before a study PEx, respectively, with all subsequent cultures negative for Pa. Children classified as 3 years' Pa negative had no Pa-positive cultures in the 36 months before a study PEx. Inverse probability of treatment weighted linear or logistic regression models were used to compare clinical outcomes (pre- to post-PEx forced expiratory volume in 1 s, odds of returning to ≥90% of baseline lung function, and odds of having a future PEx) between antipseudomonal and non-antipseudomonal antibiotic strategies. Results: Among all children included in the linked data set, 1,290 children with 2,347 PExs were eligible for analysis. Among all study PExs, 530, 326, and 1,491 were classified as 1, 2, and 3 years' Pa negative, respectively, and antipseudomonal antibiotics were administered in 79%, 67%, and 66% of all PExs classified as 1, 2, and 3 years' Pa negative, respectively. For all Pa-negative groups, when compared with non-antipseudomonal antibiotic regimens, antipseudomonal antibiotic treatment was not associated with greater improvement in any studied clinical outcome. Conclusions: Despite their common use, including antibiotics effective against Pa may provide no additional benefit for PEx treatment among children who are Pa negative for at least 1 year prior. Prospective trials are warranted to directly test this hypothesis.
Asunto(s)
Fibrosis Quística , Infecciones por Pseudomonas , Adolescente , Adulto , Antibacterianos/uso terapéutico , Niño , Fibrosis Quística/complicaciones , Fibrosis Quística/tratamiento farmacológico , Humanos , Estudios Prospectivos , Infecciones por Pseudomonas/complicaciones , Infecciones por Pseudomonas/tratamiento farmacológico , Pseudomonas aeruginosa , Estudios Retrospectivos , Adulto JovenRESUMEN
OBJECTIVES: Respiratory rate (RR) measurement is critical to diagnosing pneumonia in resource-constrained settings, but accurate RR measurement is challenging. The acute lower respiratory illness treatment and evaluation (ALRITE) mobile phone application (app), designed to help healthcare workers (HCWs) manage pediatric respiratory illnesses, includes a semiautomated RR counter. This study aimed to evaluate the accuracy and usability of the ALRITE RR counter and a commercially available RR counter app, RRate, with a reference standard. METHODS: This was a cross-sectional observational study of HCWs. Participants used both apps to measure the RR of pediatric patients from standardized videos. The reference standard was determined by consensus of a manual 1-min count by two providers. We assessed agreement using Spearman's rank correlation coefficient and constructed Bland-Altman plots to determine bias and limits of agreement. Participants completed a usability survey. RESULTS: Thirty-nine HCWs participated. The agreement between the apps and reference standard (Spearman's coefficient) was 0.83 (95% confidence interval [CI]: 0.78-0.87) for ALRITE and 0.62 (95% CI: 0.52-0.70) for RRate. ALRITE had a bias of -2 breaths/min (lower limit of agreement [LoA] -16 to +12) and RRate had a bias of -0.4 breaths/min (LoA -24 to +23) compared to the reference standard. Both apps had a poorer agreement at higher RRs. Based on usability survey responses, 95% found ALRITE easy to use. CONCLUSIONS: The ALRITE RR counter has acceptable accuracy for counting RR in infants with respiratory distress, appears to be more accurate than a commercially available option, and was user-friendly. The ALRITE RR counter is a promising tool for meriting evaluation in real-world settings.
Asunto(s)
Teléfono Celular , Aplicaciones Móviles , Infecciones del Sistema Respiratorio , Lactante , Niño , Humanos , Preescolar , Frecuencia Respiratoria , Estudios Transversales , Infecciones del Sistema Respiratorio/diagnósticoRESUMEN
Chronic Pseudomonas aeruginosa (Pa) infection is associated with increased morbidity and mortality in people with cystic fibrosis (CF). There is no gold standard definition of chronic Pa infection in CF. We compared chronic Pa definitions using encounter-based versus annualized data in the Early Pseudomonas Infection Control (EPIC) Observational study cohort, and subsequently compared annualized chronic Pa definitions across a range of U.S. cohorts spanning decades of CF care. We found that an annualized chronic Pa definition requiring at least 1 Pa+ culture in 3 of 4 consecutive years ("Green 3/4") resulted in chronic Pa metrics similar to established encounter-based modified Leeds criteria definitions, including a similar age at and proportion who fulfilled chronic Pa criteria, and a similar proportion with sustained Pa infection after meeting the chronic Pa definition. The Green 3/4 chronic Pa definition will be valuable for longitudinal analyses in cohorts with limited culture frequency.