Impact of elexacaftor-tezacaftor-ivacaftor on bacterial colonization and inflammatory responses in cystic fibrosis.

BACKGROUND: Cystic fibrosis (CF) is a multisystem disease with progressive deterioration. Recently, CF transmembrane conductance regulator (CFTR) modulator therapies were introduced that repair underlying protein defects. Objective of this study was to determine the impact of elexacaftor-tezacaftor-ivacaftor (ETI) on clinical parameters and inflammatory responses in people with CF (pwCF). METHODS: Lung function (FEV1 ), body mass index (BMI) and microbiologic data were collected at initiation and 3-month intervals for 1 year. Blood was analyzed at baseline and 6 months for cytokines and immune cell populations via flow cytometry and compared to non-CF controls. RESULTS: Sample size was 48 pwCF, 28 (58.3%) males with a mean age of 28.8 ± 10.7 years. Significant increases in %predicted FEV1 and BMI were observed through 6 months of ETI therapy with no change thereafter. Changes in FEV1 and BMI at 3 months were significantly correlated (r = 57.2, p < 0.01). There were significant reductions in Pseudomonas and Staphylococcus positivity (percent of total samples) in pwCF through 12 months of ETI treatment. Healthy controls (n = 20) had significantly lower levels of circulating neutrophils, interleukin (IL)-6, IL-8, and IL-17A and higher levels of IL-13 compared to pwCF at baseline (n = 48). After 6 months of ETI, pwCF had significant decreases in IL-8, IL-6, and IL-17A levels and normalization of peripheral blood immune cell composition. CONCLUSIONS: In pwCF, ETI significantly improved clinical outcomes, reduced systemic pro-inflammatory cytokines, and restored circulating immune cell composition after 6 months of therapy.

Transplantation and Adherence: Evaluating Tacrolimus Usage in Pediatric Patients With Cancer.

BACKGROUND: Researchers have estimated that about 50% of pediatric patients with chronic illness adhere to tacrolimus therapy, a medication responsible for preventing critical side effects in patients undergoing hematopoietic stem cell transplantation (HSCT). OBJECTIVES: The purpose of this study was to describe patient adherence to tacrolimus by reviewing documentation from the electronic health record and therapeutic drug levels. METHODS: This retrospective descriptive study examined 357 clinic visits by 57 patients undergoing HSCT. Direct (tacrolimus levels) and indirect (subjective reporting) measures were evaluated. FINDINGS: The authors found that, in 51% of visits, adherence was not documented. The overall nontherapeutic drug level rate was 60%. Because of the small sample size, nonadherence did not statistically correlate with nontherapeutic levels. The findings highlight the need for adherence awareness, assessment, and documentation in clinical practice.

The Medication Level Variability Index (MLVI) as a potential predictive biomarker of graft-versus-host disease in pediatric hematopoietic stem cell transplant patients.

The purpose of this study was to examine the potential predictive value of the Medication Level Variability Index (MLVI) biomarker with graft-versus-host disease (GVHD) in the pediatric hematopoietic stem cell transplant (HSCT) patient during the acute phase post-transplant. This retrospective descriptive study evaluated a total of 406 tacrolimus levels in 64 patients over a varying number of weeks per participant (median = 8, min = 3, max = 11). Patients were followed until Day 100 post-transplant or tacrolimus taper began. A total of 72 episodes of non-therapeutic levels occurred during the acute phase. Of those, 40 (56%) were <5, while 32 (44%) were >15. Approximately 39% (n = 25 of 64) of the participants in the study developed GVHD post-discharge. Those with GVHD had a statistically significantly higher MLVI than those that did not (median = 3.1, IQR = 2.5-4.7 vs 2.3, IQR = 1.6-3.4, respectively, P = 0.024). Using a criterion of MLVI > 3, there was a statistically significant increased likelihood of GVHD (OR = 3.82, 95% CI=1.32 = 11.04, P = 0.013). Area under the curve (AUC) calculation for the sensitivity and specificity of using the MLVI for GVHD was also conducted. The AUC of 0.67 was statistically significant (95% CI 0.53-0.81, P = 0.024). This is the first-known study to report the use of the MLVI in HSCT patients. The MLVI is associated with a main adverse outcome related to HSCT, GVHD. These results are encouraging of a new potential biomarker to evaluate tacrolimus serum assay levels and identify patients at risk for developing GVHD.

Novel Computed Tomography Scoring System for Sinus Disease in Adults With Cystic Fibrosis.

OBJECTIVE: There is no easy to use scoring system for computed tomography (CT) scans of the sinuses that is specific to cystic fibrosis (CF). We propose a simple and easily implemented scoring system to quantify severity of sinus disease in adults with CF. STUDY DESIGN: Case series with chart review. SETTING: Academic tertiary-care referral center. SUBJECTS: Sixty-nine adult patients with CF and 50 age-matched controls. METHODS: We validated a scoring system for CF sinus disease. The CT scans were interpreted by 3 physicians on 2 separate sittings. Parameters include maxillary opacification, nasal obstruction, lateral nasal wall displacement, uncinate process absence/demineralization, and presence/absence of mucocele. RESULTS: Patients with CF aged 21 to 30 years (mean = 24.7 ± 2.49). In CF cohort (n = 69), intrarater reliability for the 10 CT categories ranged from .70 to 1.00. Twenty-six (87%) were in the excellent range, and the remaining 4 (13%) were evaluated as good. In the non-CF cohort (n = 50), reliabilities ranged from .44 to 1.00. Twenty-seven (90%) were in the excellent range. For interrater reliability, in the CF cohort, 10 CT categories across the 3 raters ranged from .55 to 1.00. Excellent reliability was achieved in 15 (50%) of the observations. In the non-CF cohort, reliabilities ranged from .44 to 1.00. CONCLUSION: A novel and easy to use CT scoring system for CF sinus disease in adults was validated with inter- and intrarater reliability. This new CF sinus disease-specific scoring system can be used by clinicians, surgeons, and radiologists.

Environmental exposures and family history of asthma.

BACKGROUND: Asthma pathogenesis is a complex interaction of genetic, ethnic, environmental and social/life style risk factors. AIM: The goal of this study was to identify associations, if any, in children with asthma, between environmental risk factors (exposure to second-hand tobacco smoke (STS), pet ownership, race and a family history of asthma. METHODS: After IRB approval, from June 2011 to December 2014, 823 children with asthma were enrolled in this prospective cross sectional study. At the initial visit, families completed a questionnaire with information on family history of asthma, having a pet at home and exposure to STS by parents at home. Chi square analyses were calculated, with alpha level of significance ≤0.05. RESULTS: History of asthma in parents, siblings or grandparents was reported by 575 (69.8%) patients including father (n = 154, 17.8%) and mother (n = 235, 26.5%). Children with family history of asthma (n = 575) were significantly more likely to have a pet at home and exposure to STS (n = 347, 60.3% and n = 198, 34.4%, respectively) compared to families without a history of asthma (n = 124, 50%, p = 0.006 and n = 44, 17.7%, p < 0.001, respectively). Similarly, asthmatic children with exposure to STS (n = 241) were significantly more likely to have a pet at home and a family history of asthma (n = 153, 63.5% and n = 197, 81.7%, respectively) compared to children with no STS exposure (n = 315, 55.5%, p = 0.034 and n = 371, 65.3%, p < 0.001 respectively). CONCLUSIONS: Significantly more asthmatic children with immediate relatives with a history of asthma have a pet at home and experience STS exposure compared to children without relatives with a history of asthma, suggesting association between life style choices/environmental exposures and family history of asthma.

Screening high-risk children for asthma through a community intervention.

OBJECTIVE: Many children, particularly those from inner city neighborhoods, have undiagnosed asthma. This study was done to evaluate the effectiveness of an asthma screening, referral and follow-up intervention in an inner city community setting in early identification of children at risk for undiagnosed asthma. METHODS: A descriptive longitudinal cohort design was used to assess children at baseline and at a 2-year follow-up. Parents of children in a private day school and a church Sunday school (N = 103) completed a validated Asthma Screening Tool at both time periods. Children with asthma and at risk for asthma were referred to a primary care provider (PCP). RESULTS: At baseline, screening of 103 children, ages 3-17 years (mean=7.7 ± 2.9), were categorized as known asthma diagnosis (n = 22), at-risk for undiagnosed asthma (n = 52) and not at-risk for asthma (n = 29). Sixty-two (60.2%) parents responded to the 2-year follow-up. Referral to PCP was kept by 61.5% from the known asthma group and by 24% of children at-risk for asthma. At 2-year follow-up, among not at-risk group, no one converted to at risk status, but majority of children among known asthma group continued to have uncontrolled asthma symptoms, and very few received daily preventive asthma medications. CONCLUSIONS: The asthma screening, referral and follow-up intervention for inner city children in a community setting was successful in early identification of patients at-risk for asthma. More education for PCPs on guidelines for diagnosis and management of asthma is needed to decrease childhood asthma morbidity.

Changes in Pulmonary Function and Controlled Ventilation-High Resolution CT of Chest After Antibiotic Therapy in Infants and Young Children with Cystic Fibrosis.

BACKGROUND: Infants with cystic fibrosis (CF) develop early progressive lung disease which may be asymptomatic. Infant pulmonary function tests (IPFT) and controlled ventilation-high resolution computed tomography (CV-HRCT) of chest can detect early asymptomatic lung disease. It is not well established that these objective measures can detect changes in lung disease after clinical interventions. OBJECTIVE: The purpose of this study was to evaluate usefulness of IPFT and CV-HRCT to detect changes in lung disease after intravenous (IV) antibiotic therapy in infants with early CF-related lung disease. STUDY DESIGN: IPFTs and CV-HRCT done before and after 2 weeks of IV antibiotics in infants at our institution over the last 12 years were compared. CV-HRCTs were compared using the modified Brody scoring system. RESULTS: The sample included 21 infants, mean age 85.2 ± 47.6 weeks. Mean change in weight was 0.4 ± 0.38 kg (p = 0.001). Significant changes in IPFT included mean % predicted FEV(0.5) (+13.5 %, p = 0.043), mean %FEF(25-75) (+30.2 %, p = 0.008), mean %RV/TLC (-11.2 %, p = 0.008), and mean %FRC/TLC (-4.5 %, p = 0.001). Total Brody scores improved from a median of 10 to 5 (p < 0.001) as did mean scores for airway wall thickening (p = 0.050), air trapping (p < 0.001), and parenchymal opacities (p = 0.003). CONCLUSION: IPFT and CV-HRCT can be used as objective measures of improvement in lung disease for infants with CF treated with antibiotics.

Identification of new bacterial and fungal pathogens on surveillance bronchoscopy prior to sinus surgery in patients with cystic fibrosis.

BACKGROUND: Flexible fiberoptic bronchoscopy was performed prior to functional endoscopic sinus surgery (FESS) while under general anesthesia to collect bronchoalveolar lavage fluid (BALF) for lower respiratory tract cultures in patients with cystic fibrosis (CF). METHODS: A retrospective chart review was performed on all CF patients who underwent combined FESS and bronchoscopy between January 2009 and October 2010. Along with demographic data, bacterial, fungal, and acid fast bacillus culture data from BALF was collected and compared to oropharyngeal swab and sputum cultures obtained over the year prior to FESS and bronchoscopy. RESULTS: A total of 77 patients were enrolled with mean age 12.5 ± SD 6.5 (range 2-29) years. Mean FEV1 was 86% ±18.4 (range 33-128) % of predicted. Patients averaged 6.5 (range 1-13) sputum or OP cultures in the year prior to FESS. BALF cultures identified a new bacterial pathogen in 19% (n=15) of patients, which altered antibiotic regimen immediately in two patients and sub-acutely in five patients. BALF cultures identified a new fungal pathogen in 42% (n=32) of patients, which resulted in the addition of antifungal therapy in eight patients. BALF cultures did not identify previously undetected AFB culture positive patients. No significant differences were found between patients with and without new discoveries of bacterial or fungal pathogens with regards to key clinical demographic data, lung function parameters, healthcare utilization, or need for antibiotics over the year prior to FESS. There was no relationship between the total number of respiratory cultures obtained in the year prior to bronchoscopy and the identification of new bacterial or fungal pathogens. CONCLUSIONS: Surveillance BALF cultures obtained prior to FESS identified bacterial and fungal pathogens not previously detected by sputum or OP swab cultures in a cohort of CF patients with chronic sinus disease. Moreover, the identification of these new pathogens altered clinical management in a small number of patients.

Computed tomography correlates with improvement with ivacaftor in cystic fibrosis patients with G551D mutation.

BACKGROUND: Ivacaftor corrects the cystic fibrosis transmembrane conductance regulator (CFTR) gating defect associated with G551D mutation and is quickly becoming an important treatment in patients with cystic fibrosis (CF) due to this genetic mutation. METHODS: A single-center study was performed in CF patients receiving ivacaftor to evaluate the usefulness of high resolution computed tomography (HRCT) of the chest as a way to gauge response to ivacaftor therapy. RESULTS: Ten patients with CF were enrolled for at least one year before and after starting ivacaftor. At time of enrollment, mean age was 20.9 ± 10.8 (range 10-44) years. There were significant improvements from baseline to 6 months in mean %FVC (93 ± 16 to 99 ± 16) and %FEV1 (79 ± 26 to 87 ± 28) but reverted to baseline at one year. Mean sweat chloride levels decreased significantly from baseline to one year. Mean weight and BMI improved at 6 months. Weight continued to improve with stabilization of BMI at one year. Chest HRCT showed significant improvement at one year in mean modified Brody scores for bronchiectasis, mucous plugging, airway wall thickness, and total Brody scores. Elevated bronchiectasis and airway wall thickness scores correlated significantly with lower %FEV1, while higher airway wall thickness and mucus plugging scores correlated with more pulmonary exacerbations requiring IV and oral antibiotics respectively. CONCLUSIONS: Based on our findings, HRCT imaging is a useful tool in monitoring response to ivacaftor therapy that corrects the gating defect associated with the G551D-CFTR mutation.

Lobectomy in patients with cystic fibrosis.

BACKGROUND: Some patients with cystic fibrosis (CF) develop severe but localized lung disease or recurrent hemoptysis/pneumothorax refractory to conventional medical therapies. METHODS: The outcomes of lung resection in patients with CF and worsening localized lung disease or recurrent hemoptysis/pneumothorax refractory to conventional therapy (n=15) were evaluated by reviewing the medical records of all patients with CF followed at the CF Center at Nationwide Children's Hospital (Columbus, Ohio, USA), who underwent lobectomy over a 15-year period (1998 to 2012). RESULTS: The median age of the 15 patients (93% Caucasian) was 20 years (range two to 41 years) and their mean forced expiratory volume in 1 s (FEV1) was 59.5% of predicted one year before surgery. Three patients died within two years after lobectomy; all three deaths occurred in patients with an FEV1 ≤40% of predicted before surgery. There were no significant changes in mean height, weight, body mass index, hospital admissions or antibiotic use over time. The mean FEV1 decreased over time. Compared with at surgery, decline in FEV1 in the year before surgery was -5.4% (P=0.024) and decline in the year after surgery was -1.3% (P=0.513); however, the difference in the rate of decline was not statistically significant. CONCLUSION: In patients with CF and localized worsening bronchiectasis and/or recurrent hemoptysis/pneumothorax, lobectomy carried a significant risk of mortality, especially in patients with FEV1 ≤40% of predicted, and should only be considered when all other measures fail.

Demographics, clinical course, and outcomes of children with status asthmaticus treated in a pediatric intensive care unit: 8-year review.

OBJECTIVE: This study was done to understand the demographics, clinical course, and outcomes of children with status asthmaticus treated in a tertiary care pediatric intensive care unit (PICU). METHODS: The medical charts of all patients above 5 years of age admitted to the PICU at Nationwide Children's Hospital, Columbus, OH, USA, with status asthmaticus from 2000 to 2007 were reviewed retrospectively. Data from 222 encounters by 183 children were analyzed. RESULTS: The mean age at admission in years was 11 ± 3.8. The median PICU stay was 1 day (range, 1-12 days) and median hospital stay was 3 days. The ventilated group (n = 17) stayed a median of 2 days longer in the PICU and hospital. Nearly half of the children (n = 91; 50%) did not receive daily controller asthma medications. Adherence to asthma medications was reported in 125 patient charts of whom 43 (34%) were compliant. Exposure to smoking was reported in 167 of whom 70 (42%) were exposed. Among patients receiving metered dose inhaler (MDI), only 39 (18%) were using it with a spacer. Among 105 patient charts asthma severity data were available, of them 21 (20%) were labeled as mild intermittent, 29 (28%) were mild persistent, 26 (25%) were moderate persistent, and 29 (28%) were severe persistent. Compared to children with only one PICU admission during the study period (n = 161), children who had multiple PICU admissions (n = 22) experienced more prior emergency department visits and hospitalizations for asthma symptoms. There were no fatalities. CONCLUSION: Asthmatics with any disease severity are at risk for life-threatening asthma exacerbations requiring PICU stay, especially those who are not adherent with their daily medications.

Quality improvement study of effectiveness of cue-based feeding in infants with bronchopulmonary dysplasia in the neonatal intensive care unit.

The effectiveness and safety of experimental cue-based versus health care provider-driven (baseline) feeding strategies were evaluated in infants with bronchopulmonary dysplasia. The experimental group (n = 55) and the control group(n = 60) included infants who had been previously diagnosed with varying levels of severity of bronchopulmonary dysplasia and were identified retrospectively. Previous research was used to derive an Oral Feeding Readiness Scale as well as an Oral Feeding Quality Scale. Results validated both scales as well as the cue-based feeding strategy.

Outcomes of surgical management of severe GERD in patients with cystic fibrosis.

BACKGROUND: Patients with cystic fibrosis (CF) are at high risk for gastroesophageal reflux disease (GERD) and medical management of GERD improves pulmonary symptoms. Some patients with worsening CF and GERD symptoms undergo Nissen fundoplication, but the extent to which surgical management of GERD improves respiratory symptoms is not well studied. The purpose of this retrospective study was to evaluate the safety and efficacy of Nissen fundoplication in 48 patients with CF and uncontrolled GERD. RESULTS: Patients exhibited significantly fewer pulmonary exacerbations, increased weight gain and slower decline in % predicted FEV1 at 2 years after the surgery, compared to 2 years before surgery. Mean change in % predicted FEV1 in 2 years before surgery was--13.57% and mean change in % predicted FEV1 in 2 years after the surgery was +1.5% and difference was significant P = 0.001. Better pulmonary and nutritional outcomes were noted among patients with milder lung disease compared to those with severe lung disease, and among patients who received gastrostomy tube feedings for ≥6 months compared to those with no G-tube or tube feedings for <6 months. There was no mortality associated with surgery. CONCLUSION: In CF patients with worsening lung disease and uncontrolled GERD, Nissen fundoplication not only slows the decline in lung function but leads to significant improvement in weight, and decrease in CF exacerbations. Patients with milder disease and patients receiving G-tube feedings for ≥6 months after surgery benefited the most.

A self-report instrument that describes urogenital atrophy symptoms in breast cancer survivors.

Urogenital atrophy affects the lower urinary and genital tracts and is responsible for urinary, genital, and sexual symptoms. The accurate identification, measurement, and documentation of symptoms are limited by the absence of reliable and valid instruments. The Urogenital Atrophy Questionnaire was developed to allow self-reporting of symptoms and to provide clinicians and researchers an instrument to identify, measure, and document indicators of urogenital atrophy. A pilot study (n = 30) measured test-retest reliability (p < .05) of the instrument. Subsequently, a survey of women with (n = 168) and without breast cancer (n = 166) was conducted using the Urogenital Atrophy Questionnaire, Female Sexual Function Instrument, and Functional Assessment of Cancer Therapy, Breast, Endocrine Scale. Exploratory factor analysis (KMO 0.774; Bartlett's test of sphericity 0.000) indicated moderate-high relatedness of items. Concurrent (p > .01) and divergent validity (p < .000) were established. A questionnaire resulted that enables women, regardless of sexual orientation, partner status, and levels of sexual activity to accurately report symptoms.

Registered nurses' judgments of the classification and risk level of patient care errors.

As frontline clinicians, nurses play a critical role in mitigating patient harm, recovery from health care errors, and overall improvement of patient safety. This cross-sectional study asked nurse respondents to make judgments about the classification and severity of errors in 4 clinical vignettes. Our results showed that agreement about error classification and associated risk among registered nurses is less than optimal. Further research is needed to advance our understanding of how nurses working in complex patient care situations can improve their ability to recognize subtle cues to facilitate early recognition of potential errors.

Accuracy of vaginal symptom self-diagnosis algorithms for deployed military women.

BACKGROUND: Deployed military women have an increased risk for development of vaginitis due to extreme temperatures, primitive sanitation, hygiene and laundry facilities, and unavailable or unacceptable healthcare resources. The Women in the Military Self-Diagnosis (WMSD) and treatment kit was developed as a field-expedient solution to this problem. OBJECTIVES: The primary study aims were to evaluate the accuracy of women's self-diagnosis of vaginal symptoms and eight diagnostic algorithms and to predict potential self-medication omission and commission error rates. METHOD: Participants included 546 active duty, deployable Army (43.3%) and Navy (53.6%) women with vaginal symptoms who sought healthcare at troop medical clinics on base.In the clinic lavatory, women conducted a self-diagnosis using a sterile cotton swab to obtain vaginal fluid, a FemExam card to measure positive or negative pH and amines, and the investigator-developed WMSD Decision-Making Guide. Potential self-diagnoses were "bacterial infection" (bacterial vaginosis [BV] and/or trichomonas vaginitis [TV]), "yeast infection" (candida vaginitis [CV]), "no infection/normal," or "unclear." The Affirm VPIII laboratory reference standard was used to detect clinically significant amounts of vaginal fluid DNA for organisms associated with BV, TV, and CV. RESULTS: Women's self-diagnostic accuracy was 56% for BV/TV and 69.2% for CV. False-positives would have led to a self-medication commission error rate of 20.3% for BV/TV and 8% for CV. Potential self-medication omission error rates due to false-negatives were 23.7% for BV/TV and 24.8% for CV. The positive predictive value of diagnostic algorithms ranged from 0% to 78.1% for BV/TV and 41.7% for CV. DISCUSSION: The algorithms were based on clinical diagnostic standards. The nonspecific nature of vaginal symptoms, mixed infections, and a faulty device intended to measure vaginal pH and amines explain why none of the algorithms reached the goal of 95% accuracy. The next prototype of the WMSD kit will not include nonspecific vaginal signs and symptoms in favor of recently available point-of-care devices that identify antigens or enzymes of the causative BV, TV, and CV organisms.

Children's adjustment to parental cancer: a theoretical model development.

There is growing empirical evidence that various child and family factors are associated with children's reactions to parental cancer. Children having parents with cancer may respond to parental cancer in different ways in terms of bonadjustment and maladjustment. Children's maladjustment to this pervasive stressor is manifested by a wide variety of physiologic, psychologic, and behavioral stress responses. To date, research on children's adjustment to parental cancer has focused almost exclusively on documenting children's adjustment problems and on describing simple, direct association between the characteristics of children and/or their families, and children's adjustment. The gap in research and clinical practice lies in the lack of a comprehensive model to illuminate children's coping with parental cancer and to guide intervention programs. Based on a synthesis of the literature, this article proposes a model that specifies the relationships among the stressor of having a parent with cancer, moderators and mediator variables, and adjustment. This model can serve as a basis for future research and intervention programs.

Measures of overweight status in school-age children.

Identifying and intervening with overweight children may decrease their likelihood of developing heart disease later in life. This secondary analysis of 58 children in the 3rd grade examined the prevalence of overweight children, methods for measuring overweight status, and the relationship among these measures and other risk factors for heart disease. Approximately one third of the 58 children were categorized as overweight. Several measures, such as weight, body fat percentage, body mass index (BMI), and skin-fold, are available to school nurses for measuring overweight status. The highest correlations were between BMI and weight and between BMI and body fat. Anthropometric measurements cannot predict cholesterol level, 24-hour diet recall, or family history. Blood pressure can be predicted by weight, body fat percentage, and BMI. BMI and body fat percentage highly correlate; however, body fat percentage is more liberal in identifying children at risk for overweight status. Therefore, body fat percentage is recommended for identification of overweight status in school-age children.