RESUMEN
BACKGROUND: Treatment of pulmonary exacerbations (PEx) in cystic fibrosis (CF) varies widely with no consensus on management practices or best indicators of therapeutic success. To design trials evaluating PEx treatment factors, we characterise the heterogeneity of PEx care in adults and paediatrics, and correlate it with measures of clinical response including short-term and long-term lung function changes, change in symptom severity score and time to next intravenous antibiotic therapy. METHODS: Data were used from a prospective observational study of patients with CF ≥10â years of age enrolled at six sites between 2007 and 2010. All were started on intravenous antibiotics for a clinically diagnosed PEx. Analysis of variance, logistic and Cox regression were used to examine the association of treatment factors with short-term and long-term clinical response. RESULTS: Of 123 patients with CF (60% women, aged 23.1±10.2â years), 33% experienced <10% relative improvement in FEV1 during treatment, which was associated with failing to recover baseline lung function 3â months after treatment (OR=7.8, 95% CI 1.9 to 31.6, p=0.004) and a longer time to next intravenous antibiotic (HR=0.48, 95% CI 0.27 to 0.85, p=0.011). Symptom improvement was observed but was not associated with subsequent lung function or time to next antibiotic therapy, which had a median recurrence time of 143â days. CONCLUSIONS: Immediate symptomatic or respiratory response to PEx treatment did not have a clear relationship with subsequent outcomes such as lung function or intravenous antibiotic-free interval. These results can inform future research of treatment regimens for PEx in terms of interventions and outcome measures. TRIAL REGISTRATION: NCT00788359 (www.clinicaltrials.gov).
Asunto(s)
Antibacterianos/administración & dosificación , Fibrosis Quística/tratamiento farmacológico , Volumen Espiratorio Forzado/fisiología , Pulmón/fisiopatología , Administración por Inhalación , Administración Oral , Adolescente , Niño , Fibrosis Quística/fisiopatología , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Estudios Prospectivos , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Pseudomonas aeruginosa (Pa) is the most important pathogen infecting the airways in individuals with cystic fibrosis. A key question is whether children with newly acquired Pa infection who are able to achieve sustained eradication after early antipseudomonal therapy demonstrate improved long-term health outcomes compared with those who are unable to achieve a sustained microbiologic response. METHODS: This cohort study utilized observational follow-up data on children participating in the Early Pseudomonas Infection Control trial who received standardized therapy for newly acquired Pa. Sustained eradicators were defined as those who maintained Pa-negative cultures for 12 months after initial antipseudomonal therapy. Associations between eradication status and outcomes were assessed. RESULTS: Of the 249 trial participants included in the study, 172 (69%) achieved sustained eradication of Pa during the trial (sustained eradicators). Over the median 5-year follow-up, sustained eradicators had a 74% reduced risk of developing chronic Pa (hazard ratio [HR], 0.26; 95% confidence interval [CI], .17-.40) and a 57% reduced risk of mucoidy (HR, 0.43; 95% CI, .25-.73) compared with nonsustained eradicators. Sustained eradicators had significantly less anti-Pa antibiotic usage during follow-up compared with nonsustained eradicators. There was no association between eradication status and clinical outcomes including rate of exacerbation and lung function decline. CONCLUSIONS: This is the first study to quantify the long-term durability of microbiological response associated with early antipseudomonal therapy, demonstrating the critical importance of optimizing antipseudomonal therapies during early Pa infection. The clinical impact of failure to achieve sustained Pa eradication remains unclear, however, and may be confounded by anti-Pa antibiotic usage. CLINICAL TRIALS REGISTRATION: NCT00097773.
Asunto(s)
Antibacterianos/uso terapéutico , Fibrosis Quística/epidemiología , Fibrosis Quística/microbiología , Infecciones por Pseudomonas/tratamiento farmacológico , Infecciones por Pseudomonas/epidemiología , Pseudomonas aeruginosa , Antibacterianos/administración & dosificación , Niño , Preescolar , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Humanos , Lactante , Masculino , Infecciones por Pseudomonas/complicaciones , Infecciones por Pseudomonas/fisiopatología , Resultado del TratamientoRESUMEN
BACKGROUND: Healthcare organizations are implementing innovative ways to deliver patient centered care, which includes the addition of the orthopedic nurse navigator role. PURPOSE: The purpose of this study was to examine length of hospital stay and patient satisfaction following the implementation of an orthopedic surgery CNS-patient navigator. METHODS: This prospective descriptive study (n = 226) examined length of stay, location of discharge, and readmission to hospital by reviewing the participants' electronic hospital record. Patient satisfaction was examined by telephone using the Patient Satisfaction with Interpersonal Relationship with Navigator scale, and generic health related quality of life and patient experience were measured by the howRu/howRwe scale. RESULTS: The mean length of hospital stay was 2.8 (±1.0), which was less than the provincial mean length of stay for the same time period. The majority of participants were discharged to home, and only 1.3% of participants were readmitted to the same hospital within 30 days following discharge. All participants were satisfied with the care they received from the navigator, and reported a positive patient experience and health related quality of life. CONCLUSION: The mean length of stay in our hospital was lower than the provincial mean. Participants were satisfied with the care provided by the navigator.
Asunto(s)
Artroplastia de Reemplazo de Rodilla , Navegación de Pacientes , Artroplastia de Reemplazo de Cadera , Humanos , Tiempo de Internación , Alta del Paciente , Satisfacción del Paciente , Satisfacción Personal , Estudios Prospectivos , Calidad de VidaRESUMEN
OBJECTIVES: To evaluate clinical outcomes associated with initial isolation of Pseudomonas aeruginosa (Pa) in a large U.S. cystic fibrosis (CF) cohort in the current era of widespread early Pa eradication therapy. METHODS: Participants were children with CF enrolled in the Early Pseudomonas Infection Control (EPIC) Observational Study who had no isolation of Pa from respiratory cultures prior to enrollment. Population-averaged regression models using generalized estimating equation methods were used to estimate the effect of Pa acquisition on endpoints including lung function, growth, pulmonary exacerbation rate, respiratory signs and symptoms, and respiratory cultures. RESULTS: Eight hundred thirty-eight subjects were observed for a mean 4.6 (SD 1.2) years during which 431 (51%) acquired Pa. There was no statistically significant effect of Pa acquisition on the slopes of FEV1 % predicted or growth parameters. Pulmonary exacerbation rate was statistically significantly greater after Pa acquisition (incident rate ratio 1.40, 95% CI 1.07, 1.84) as were odds of crackles or wheeze on physical exam (OR 1.23, 95% CI 1.00, 1.52). Odds of isolation of MRSA (OR 1.86, 95% CI 1.38, 2.49) and S. maltophilia (OR 2.11, 95% CI 1.49, 2.98) increased after Pa acquisition, while the odds of H. influenzae (OR 0.54, 95% CI 0.46, 0.64) decreased. CONCLUSIONS: In this large U.S. cohort, we did not detect an association between acquisition of Pa and deterioration in lung function or nutrition. Pa acquisition was associated with significantly increased pulmonary exacerbation rate and odds of crackles or wheeze. Pa infection may be the cause of these outcomes or a marker of more severe disease.
Asunto(s)
Fibrosis Quística/microbiología , Infecciones por Pseudomonas/epidemiología , Ruidos Respiratorios/etiología , Achromobacter denitrificans/aislamiento & purificación , Niño , Fibrosis Quística/epidemiología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Staphylococcus aureus Resistente a Meticilina/aislamiento & purificación , Stenotrophomonas maltophilia/aislamiento & purificación , Estados Unidos/epidemiologíaRESUMEN
RATIONALE: Methicillin-resistant Staphylococcus aureus (MRSA) prevalence continues to increase in patients with cystic fibrosis (CF) in the United States, reaching 26.5% in 2012. Approximately 30% of strains are SCCmec (staphylococcal cassette chromosome mec) IV type, frequently USA300, which in the general population have different genotypic and phenotypic features than SCCmec II type. OBJECTIVES: We hypothesized that risk factors for acquisition and outcomes in patients with CF differed for "health care-associated" (SCCmec II) versus "community-associated" (SCCmec IV) MRSA strains. METHODS: To determine the role of SCCmec type and Panton-Valentine leukocidin (PVL), MRSA isolates from patients not more than 18 years old at seven CF centers were typed and the association of potential risk factors and subsequent clinical course was assessed, using data provided by the CF Patient Registry. MEASUREMENTS AND MAIN RESULTS: Participants with chronic MRSA (295) had typeable isolates and clinical data; 205 (69.5%) had SCCmec II PVL(-), 39 (13.2%) had SCCmec IV PVL(-), and 51 (17.3%) had SCCmec IV PVL(+) strains. SCCmec IV, compared with SCCmec II, increased during the study period, 1996-2010 (P = 0.03). SCCmec II was associated with Pseudomonas aeruginosa-positive cultures and three or more clinic visits in the 6 months preceding the first positive MRSA culture (adjusted odds ratio, 2.05; 95% confidence interval, 1.13-3.74; P = 0.019). Lung function and anthropometrics remained unchanged in the 6 months after initial MRSA detection compared with the 6 months prior. Although CF care increased for participants in both groups in the 6 months after MRSA detection, inhaled antibiotics were prescribed more frequently in those with SCCmec II strains and increased hospitalizations occurred in those with SCCmec IV PVL(-) strains compared with those with PVL(+) strains (adjusted difference, 34.10%; 95% confidence interval, 7.58-60.61; P = 0.012). Participants in both groups had an increase in CF care in the 2 years after MRSA detection compared with the 2 years prior. CONCLUSIONS: Increased exposure to CF clinics and P. aeruginosa may constitute risk factors for acquisition of SCCmec II MRSA strains. Clinical interventions increased 6 months and 2 years after initial MRSA detection regardless of SCCmec type.
Asunto(s)
Antibacterianos/uso terapéutico , Fibrosis Quística , Staphylococcus aureus Resistente a Meticilina , Pseudomonas aeruginosa/aislamiento & purificación , Infecciones Estafilocócicas , Adolescente , Toxinas Bacterianas/análisis , Niño , Preescolar , Coinfección , Fibrosis Quística/complicaciones , Fibrosis Quística/diagnóstico , Fibrosis Quística/epidemiología , Fibrosis Quística/microbiología , ADN Bacteriano/análisis , Exotoxinas/análisis , Femenino , Técnicas de Genotipaje , Humanos , Leucocidinas/análisis , Masculino , Staphylococcus aureus Resistente a Meticilina/genética , Staphylococcus aureus Resistente a Meticilina/aislamiento & purificación , Infecciones por Pseudomonas/complicaciones , Infecciones por Pseudomonas/diagnóstico , Sistema de Registros , Pruebas de Función Respiratoria , Factores de Riesgo , Infecciones Estafilocócicas/diagnóstico , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/etiología , Estados Unidos/epidemiología , Factores de Virulencia/análisisRESUMEN
This study explored the association between personal resilience and distress, coping, and diabetes outcomes in 50 adolescents with type 1 diabetes. Resilience was defined by a factor score derived from validated instruments measuring self-efficacy, optimism, and self-esteem. Variable- and person-focused methodologies were used to explore these associations. Low resilience was associated with higher distress, poor quality of life, and poor glycemic control. Participants with low resilience used more maladaptive coping strategies and were at greatest risk of poor outcomes. Findings suggest that resilience is a promising candidate for interventions designed to reduce distress and improve outcomes for adolescents with type 1 diabetes.
Asunto(s)
Adaptación Psicológica , Diabetes Mellitus Tipo 1/psicología , Progresión de la Enfermedad , Resiliencia Psicológica , Estrés Psicológico/psicología , Adolescente , Femenino , Humanos , MasculinoRESUMEN
RATIONALE: In cystic fibrosis (CF), pulmonary exacerbations present an opportunity to define the effect of antibiotic therapy on systemic measures of inflammation. OBJECTIVES: Investigate whether plasma inflammatory proteins demonstrate and predict a clinical response to antibiotic therapy and determine which proteins are associated with measures of clinical improvement. METHODS: In this multicenter study, a panel of 15 plasma proteins was measured at the onset and end of treatment for pulmonary exacerbation and at a clinically stable visit in patients with CF who were 10 years of age or older. MEASUREMENTS AND MAIN RESULTS: Significant reductions in 10 plasma proteins were observed in 103 patients who had paired blood collections during antibiotic treatment for pulmonary exacerbations. Plasma C-reactive protein, serum amyloid A, calprotectin, and neutrophil elastase antiprotease complexes correlated most strongly with clinical measures at exacerbation onset. Reductions in C-reactive protein, serum amyloid A, IL-1ra, and haptoglobin were most associated with improvements in lung function with antibiotic therapy. Having higher IL-6, IL-8, and α1-antitrypsin (α1AT) levels at exacerbation onset were associated with an increased risk of being a nonresponder (i.e., failing to recover to baseline FEV1). Baseline IL-8, neutrophil elastase antiprotease complexes, and α1AT along with changes in several plasma proteins with antibiotic treatment, in combination with FEV1 at exacerbation onset, were predictive of being a treatment responder. CONCLUSIONS: Circulating inflammatory proteins demonstrate and predict a response to treatment of CF pulmonary exacerbations. A systemic biomarker panel could speed up drug discovery, leading to a quicker, more efficient drug development process for the CF community.
Asunto(s)
Antibacterianos/uso terapéutico , Fibrosis Quística/tratamiento farmacológico , Inflamación/tratamiento farmacológico , Pulmón/fisiopatología , Adolescente , Biomarcadores/metabolismo , Proteína C-Reactiva/metabolismo , Niño , Fibrosis Quística/metabolismo , Fibrosis Quística/fisiopatología , Citocinas/metabolismo , Progresión de la Enfermedad , Femenino , Volumen Espiratorio Forzado , Humanos , Inflamación/metabolismo , Inflamación/fisiopatología , Masculino , PronósticoRESUMEN
BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) infects â¼25% of patients with cystic fibrosis (CF) in the United States. We hypothesized that health-related outcomes differed between healthcare-associated (staphylococcal cassette chromosome mec [SCCmec] II) vs community-associated (SCCmec IV) MRSA strains in patients chronically infected with CF. METHODS: At 7 CF centers, MRSA isolates were prospectively obtained from patients ≤18 years old with 2 or more positive MRSA cultures within 1 year. Isolates were classified by SCCmec type and Panton-Valentine-leukocidin (PVL) status at a core laboratory, and sites remained blinded to SCCmec type and PVL results. Prospective clinical data including antibiotic use, respiratory symptoms, and pulmonary exacerbations were obtained. RESULTS: Among the 295 cohort participants with typeable MRSA isolates, 69.5% had SCCmec II PVL(-), 13.2% had SCCmec IV PVL(-), and 17.3% had SCCmec IV PVL(+) strains. During follow-up of 287 patients with prospective data after enrollment, the risk for pulmonary exacerbations was significantly higher among participants with SCCmec II than SCCmec IV strains (risk ratio [RR] = 1.13; P = .03) and higher in those with SCCmec IV PVL(-) than SCCmec IV PVL(+) strains (RR = 1.62; P < .0001). Neither decline in lung function nor changes in nutritional outcomes differed by SCCmec type or PVL status during the study period. CONCLUSIONS: Participants harboring chronic SCCmec II MRSA received more antibiotics and may have more lung disease than those with SCCmec IV; PVL(+) isolates were not associated with more advanced disease.
Asunto(s)
Antibacterianos/administración & dosificación , Fibrosis Quística/complicaciones , Staphylococcus aureus Resistente a Meticilina , Infecciones Estafilocócicas/complicaciones , Infecciones Estafilocócicas/tratamiento farmacológico , Adolescente , Antibacterianos/efectos adversos , Toxinas Bacterianas , Niño , Preescolar , Enfermedad Crónica , Fibrosis Quística/tratamiento farmacológico , Exotoxinas , Femenino , Humanos , Leucocidinas , Masculino , Staphylococcus aureus Resistente a Meticilina/clasificación , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Staphylococcus aureus Resistente a Meticilina/aislamiento & purificación , Infecciones del Sistema Respiratorio/tratamiento farmacológico , Infecciones del Sistema Respiratorio/etiología , Resultado del Tratamiento , Estados UnidosRESUMEN
RATIONALE: The Early Pseudomonal Infection Control (EPIC) randomized trial rigorously evaluated the efficacy of different antibiotic regimens for eradication of newly identified Pseudomonas (Pa) in children with cystic fibrosis (CF). Protocol based therapy in the trial was provided based on culture positivity independent of symptoms. It is unclear whether outcomes observed in the clinical trial were different than those that would have been observed with historical standard of care driven more heavily by respiratory symptoms than culture positivity alone. We hypothesized that the incidence of Pa recurrence and hospitalizations would be significantly reduced among trial participants as compared to historical controls whose standard of care preceded the widespread adoption of tobramycin inhalation solution (TIS) as initial eradication therapy at the time of new isolation of Pa. METHODS: Eligibility criteria from the trial were used to derive historical controls from the Epidemiologic Study of CF (ESCF) who received standard of care treatment from 1995 to 1998, before widespread availability of TIS. Pa recurrence and hospitalization outcomes were assessed over a 15-month time period. RESULTS: As compared to 100% of the 304 trial participants, only 296/608 (49%) historical controls received antibiotics within an average of 20 weeks after new onset Pa. Pa recurrence occurred among 104/298 (35%) of the trial participants as compared to 295/549 (54%) of historical controls (19% difference, 95% CI: 12%, 26%, P < 0.001). No significant differences in the incidence of hospitalization were observed between cohorts. CONCLUSIONS: Protocol-based antimicrobial therapy for newly acquired Pa resulted in a lower rate of Pa recurrence but comparable hospitalization rates as compared to a historical control cohort less aggressively treated with antibiotics for new onset Pa.
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Antibacterianos/uso terapéutico , Fibrosis Quística/tratamiento farmacológico , Hospitalización/estadística & datos numéricos , Infecciones por Pseudomonas/tratamiento farmacológico , Pseudomonas aeruginosa/efectos de los fármacos , Tobramicina/uso terapéutico , Administración por Inhalación , Antibacterianos/administración & dosificación , Niño , Preescolar , Fibrosis Quística/microbiología , Femenino , Humanos , Lactante , Masculino , Estudios Prospectivos , Recurrencia , Tobramicina/administración & dosificación , Resultado del TratamientoRESUMEN
BACKGROUND: Risk factors for initial Pseudomonas aeruginosa (Pa) acquisition, particularly environmental exposures, are poorly understood. We aimed to identify such risk factors in order to inform prevention strategies and identify high-risk populations. METHODS: The study cohort included all participants in the U.S. EPIC Observational Study who had no prior Pa-positive respiratory cultures (N=889). Cox proportional hazard models were used to test the effects of factors on age at first Pa-positive respiratory culture. RESULTS: Cystic fibrosis (CF) genotype functional class had an important effect on age at initial Pa acquisition (hazard ratio (HR) comparing minimal to residual CFTR function 2.87 (95% CI 1.88, 4.39)). None of the modifiable risk factors evaluated, including cigarette smoke, hot tub use, breastfeeding, or daycare, was associated with age at Pa acquisition. Similarly, newborn screening was not associated with age at Pa acquisition (HR 0.85, 95% CI 0.66, 1.09). Key associations were validated in a CF Foundation National Patient Registry replication cohort. CONCLUSIONS: Given the ubiquitous presence of Pa in the environment, it may be that many imposed lifestyle changes will have less impact on age at initial Pa acquisition than genetic determinants.
Asunto(s)
Fibrosis Quística , Exposición a Riesgos Ambientales , Infecciones por Pseudomonas , Pseudomonas aeruginosa/aislamiento & purificación , Edad de Inicio , Niño , Preescolar , Estudios de Cohortes , Fibrosis Quística/epidemiología , Fibrosis Quística/genética , Fibrosis Quística/microbiología , Fibrosis Quística/fisiopatología , Regulador de Conductancia de Transmembrana de Fibrosis Quística/genética , Exposición a Riesgos Ambientales/clasificación , Exposición a Riesgos Ambientales/estadística & datos numéricos , Etnicidad , Femenino , Interacción Gen-Ambiente , Humanos , Lactante , Recién Nacido , Masculino , Tamizaje Neonatal/métodos , Modelos de Riesgos Proporcionales , Infecciones por Pseudomonas/epidemiología , Infecciones por Pseudomonas/microbiología , Infecciones por Pseudomonas/fisiopatología , Infecciones del Sistema Respiratorio/epidemiología , Infecciones del Sistema Respiratorio/microbiología , Infecciones del Sistema Respiratorio/fisiopatología , Factores de Riesgo , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND: While the mechanism of action by which azithromycin exerts positive effects inpatients with cystic fibrosis remains unclear, evidence suggests that azithromycin may act as an immunomodulatory agent. We examined changes in systemic inflammatory markers in a doubleblind, randomized, controlled trial of oral azithromycin in patients 6-18 years of age with cystic fibrosis who were uninfected with Pseudomonas aeruginosa. METHODS: WBC counts and differential, serum myeloperoxidase (MPO), high-sensitivity C reactive protein (hsCRP), intracellular adhesion molecule 1, IL-6, calprotectin, serum amyloid A (SAA),and granulocyte colony-stimulating factor (G-CSF) were measured at baseline and after 28 and 168 days of treatment in patients receiving either oral azithromycin or placebo. RESULTS: Inflammatory markers were similar in both groups at baseline. HsCRP, MPO, SAA, calprotectin,and the absolute neutrophil count (ANC) significantly decreased from baseline today 28 in the azithromycin group compared with the placebo group ( P < .05). This treatment effect was sustained at day 168 for ANC, calprotectin, and SAA ( P < .05). Changes in hsCRP, calprotectin,and SAA at day 28 were negatively correlated with changes in FEV 1 (L) and FEV 1(% predicted), as well as both absolute and relative changes in weight ( P < .05). Except for weight (%),the associations remained significant for calprotectin; FEV 1 (L) and weight (%) remained significantly correlated with the 168-day change in hsCRP. The 168-day change in ANC was significantly correlated with changes in lung function, but not in weight; the change in G-CSF was significantly correlated with the change in weight (%) only. CONCLUSIONS: In patients not infected with P aeruginosa , oral azithromycin significantly reduced neutrophil counts and serum inflammatory markers within 28 days of initiating treatment. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT00431964; URL: www.clinicaltrials.gov