Real World Experience of Pseudomonas aeruginosa Eradication at an Urban Pediatric Cystic Fibrosis Center.

OBJECTIVES: Clinical practice guidelines for eradication of Pseudomonas aeruginosa (PA) in patients with cystic fibrosis (CF) have been established, but current studies have not assessed how these guidelines translate into clinical practice. This study aimed to characterize the real-world eradication strategies, eradication rates, and microbiologic outcomes of patients with first acquisition of PA at an urban pediatric CF center. METHODS: The Cystic Fibrosis Foundation Patient Registry was used to identify patients with CF who received care between January 2014 and September 2018 and had PA isolated from an airway culture. Patients were included if they had a first positive PA culture or the first positive culture in 2 years. Data regarding patient demographics, timing and results of airway cultures, and treatment regimens were collected. RESULTS: Over a 3.75-year period, 75 patients had an initial positive culture for PA. Of those patients, 74 (98.7%) received eradication treatment. Tobramycin inhalation solution (TIS) monotherapy was the most common regimen prescribed (52.7%) followed by TIS plus an oral fluoroquinolone (28.4%) (TIS + FQ). Of those treated, 62 (83.8%) patients had eradication of PA at first follow-up culture (median, 58 days; IQR, 49-77 days). Eradication rates (84.6% vs 76.2%, p = 0.421) and times to recurrence (6.37 months vs 5.1 months, p = 0.726) were comparable between TIS and TIS + FQ cohorts. CONCLUSIONS: The eradication rate for PA in clinical practice is similar to that published in the literature. Consistent with published guidelines, these microbiologic outcomes do not support the addition of an oral FQ to TIS for initial PA eradication.

Cystic Fibrosis Diagnostic Challenges over 4 Decades: Historical Perspectives and Lessons Learned.

OBJECTIVE: Because cystic fibrosis (CF) can be difficult to diagnose, and because information about the genetic complexities and pathologic basis of the disease has grown so rapidly over the decades, several consensus conferences have been held by the US CF Foundation, and a variety of other efforts to improve diagnostic practices have been organized by the European CF Society. Despite these efforts, the application of diagnostic criteria has been variable and caused confusion. STUDY DESIGN: To improve diagnosis and achieve standardization in terms and definitions worldwide, the CF Foundation in 2015 convened a committee of 32 experts in the diagnosis of CF from 9 countries. As part of the process, all previous consensus-seeking exercises sponsored by the CF Foundation, along with the important efforts of the European CF Society, were comprehensively and critically reviewed. The goal was to better understand why consensus conferences and their publications have not led to the desired results. RESULTS: Lessons learned from previous diagnosis consensus processes and products were identified. It was decided that participation in developing a consensus was generally not inclusive enough for global impact. It was also found that many efforts to address sweat test issues were valuable but did not always improve clinical practices as CF diagnostic testing evolved. It also became clear from this review that premature applications of potential diagnostic tests such as nasal potential difference and intestinal current measurement should be avoided until validation and standardization occur. Finally, we have learned that due to the significant and growing number of cases that are challenging to diagnose, an associated continuing medical education program is both desirable and necessary. CONCLUSIONS: It is necessary but not sufficient to organize and publish CF diagnosis consensus processes. Follow-up implementation efforts and monitoring practices seem essential.

Republished paper: assessing and improving safety culture throughout an academic medical centre: a prospective cohort study.

OBJECTIVES To describe the authors' hospital-wide efforts to improve safety climate at a large academic medical centre. DESIGN AND SETTING A prospective cohort study used multiple interventions to improve hospital-wide safety climate. 144 clinical units in an urban academic medical centre are included in this analysis. Interventions The comprehensive unit-based safety programme included steps to identify hazards, partner units with a senior executive to fix hazards, learn from defects, and implement communication and teamwork tools. Hospital-level interventions were also implemented. Main outcome measures Safety climate was assessed annually using the safety attitudes questionnaire. The safety culture goal was to meet or exceed the 60% minimum positive score or improve the score by ≥10 points. RESULTS Response rates were 77% (2006) and 79% (2008). For safety climate, 55% of units in 2006 and 82% in 2008 achieved the culture goal. For teamwork climate, 61% of units in 2006 and 83% in 2008 achieved the culture goal. The mean safety climate improvement (difference score) for 79 units at or above 60% in 2006 was 0.201 in 2008; the mean improvement for the 65 units below the threshold was 18.278. The mean teamwork climate improvement (difference score) for the 89 units at or above 60% in 2006 was 0.452 in 2008; the mean improvement for the 55 units below the threshold was 16.176. Climate scores improved significantly from 2006 to 2008 in every domain except stress recognition. CONCLUSIONS Hospital-wide interventions were associated with improvements in safety climate at a large academic medical centre.

Assessing and improving safety culture throughout an academic medical centre: a prospective cohort study.

OBJECTIVES: To describe the authors' hospital-wide efforts to improve safety climate at a large academic medical centre. DESIGN AND SETTING: A prospective cohort study used multiple interventions to improve hospital-wide safety climate. 144 clinical units in an urban academic medical centre are included in this analysis. INTERVENTIONS: The comprehensive unit-based safety programme included steps to identify hazards, partner units with a senior executive to fix hazards, learn from defects, and implement communication and teamwork tools. Hospital-level interventions were also implemented. MAIN OUTCOME MEASURES: Safety climate was assessed annually using the safety attitudes questionnaire. The safety culture goal was to meet or exceed the 60% minimum positive score or improve the score by ≥10 points. RESULTS: Response rates were 77% (2006) and 79% (2008). For safety climate, 55% of units in 2006 and 82% in 2008 achieved the culture goal. For teamwork climate, 61% of units in 2006 and 83% in 2008 achieved the culture goal. The mean safety climate improvement (difference score) for 79 units at or above 60% in 2006 was 0.201 in 2008; the mean improvement for the 65 units below the threshold was 18.278. The mean teamwork climate improvement (difference score) for the 89 units at or above 60% in 2006 was 0.452 in 2008; the mean improvement for the 55 units below the threshold was 16.176. Climate scores improved significantly from 2006 to 2008 in every domain except stress recognition. CONCLUSIONS: Hospital-wide interventions were associated with improvements in safety climate at a large academic medical centre.

Transient effectiveness of vitamin D2 therapy in pediatric cystic fibrosis patients.

BACKGROUND: The effectiveness of current treatment recommendations for vitamin D insufficiency in children with CF is unknown. Therefore, we assessed the effectiveness of vitamin D(2) 50,000 IU once daily for 28 days for vitamin D insufficiency. METHODS: Retrospective chart review of pediatric CF patients from 2006-2008. Vitamin D(2) 50,000 IU daily for 28 days was given to patients with 25-OHD <30 ng/mL and repeat 25-OHD levels were obtained after completion of therapy. RESULTS: One hundred forty-seven levels from 97 individuals were assessed. Success of treatment was 54% (n=80/147). Seventeen of 39 patients (43%) followed for an additional 6-18 months were able to maintain levels of >or=30 ng/mL. CONCLUSIONS: Vitamin D(2) 50,000 IU daily for 28 days was effective in correcting vitamin D insufficiency in approximately 50% of subjects. However, almost half of successfully treated patients were unable to maintain normal 25-OHD levels >6 months after completion of therapy, implying that this effect is transient.

Description of a standardized nutrition classification plan and its relation to nutritional outcomes in children with cystic fibrosis.

OBJECTIVE: Better nutrition enhances lung function and increases survival for children with cystic fibrosis (CF). Therefore, we developed a standardized strategy to evaluate nutritional status and create individualized treatment plans to ensure that all patients received the same high-quality care in a busy CF Center. METHODS: A quality improvement approach was undertaken to develop a novel nutrition classification strategy to identify and treat children with subtle manifestations of nutritional deficits in addition to those with obvious nutritional issues. RESULTS: During the 15-month study period, the median body mass index (BMI) percentile increased from 35.2 (0-95.9) to 42.0 (0-97.7), p < .005. Additionally, the number of children with a BMI >or=50th percentile increased by 11.8%. CONCLUSIONS: Adoption of a standardized approach to nutritional assessment and treatment led to significant improvement in nutritional outcomes of CF patients, demonstrating that systematic changes in clinical practice can improve clinical outcomes substantially over a short period of time.

Primary snoring and growth failure in a patient with cystic fibrosis.

An 8-year-old female with pancreatic-insufficiency cystic fibrosis presented with recurrent pharyngitis, and reduction in body mass index and height velocity during the previous 2 years. Her symptoms (eg, snoring and restless sleep) suggested obstructive sleep apnea, and physical examination revealed tonsillar hypertrophy. While her respiratory disturbance index on nocturnal polysomnography was normal, there was evidence of prolonged periods of snoring, associated with hypercapnia. Adenotonsillectomy decreased the snoring, improved her sleep, and in the 18-month follow-up period she had substantial weight-gain and growth improvement. This case demonstrates that adenotonsillar hypertrophy associated with recurrent pharyngitis and primary snoring might hinder growth in a patient with cystic fibrosis.

Guidelines for diagnosis of cystic fibrosis in newborns through older adults: Cystic Fibrosis Foundation consensus report.

Newborn screening (NBS) for cystic fibrosis (CF) is increasingly being implemented and is soon likely to be in use throughout the United States, because early detection permits access to specialized medical care and improves outcomes. The diagnosis of CF is not always straightforward, however. The sweat chloride test remains the gold standard for CF diagnosis but does not always give a clear answer. Genotype analysis also does not always provide clarity; more than 1500 mutations have been identified in the CF transmembrane conductance regulator (CFTR) gene, not all of which result in CF. Harmful mutations in the gene can present as a spectrum of pathology ranging from sinusitis in adulthood to severe lung, pancreatic, or liver disease in infancy. Thus, CF identified postnatally must remain a clinical diagnosis. To provide guidance for the diagnosis of both infants with positive NBS results and older patients presenting with an indistinct clinical picture, the Cystic Fibrosis Foundation convened a meeting of experts in the field of CF diagnosis. Their recommendations, presented herein, involve a combination of clinical presentation, laboratory testing, and genetics to confirm a diagnosis of CF.

Paying the piper: investing in infrastructure for patient safety.

BACKGROUND: Although the best allocation of resources is unknown, there is general agreement that improvements in safety require an organization-level safety culture, in which leadership humbly acknowledges safety shortcomings and allocates resources at the patient care and unit levels to identify and mitigate risks. Since 2001, the Johns Hopkins Hospital has increased its investment in human capital at the patient care, unit/team, and organization levels to improve patient safety. PATIENT CARE LEVEL: An inadequate infrastructure, both technical and human, has prompted health care organizations to rely on nurses to help implement new safety programs and to enforce new policies because hospital leaders often have limited ability to disseminate or enforce such changes with the medical staff. UNIT OR TEAM LEVEL: At the team or nursing unit level, there is little or no infrastructure to develop, implement, and monitor safety projects. There is limited unit-level support for safety projects, and the resources that are allocated come from overtaxed department budgets. ORGANIZATION LEVEL: HOSPITAL LEVEL AND HEALTH SYSTEM: Infrastructure is needed to design, implement, and evaluate the following domains of work-measuring progress in patient safety, translating evidence into practice, identifying and mitigating hazards, improving culture and communication, and identifying an infrastructure in the organization for patient safety efforts. REFLECTIONS: Fulfilling a commitment to safe and high-quality care will not be possible without significant investment in patient safety infrastructure. Health care organizations will need to determine the cost-benefit ratio of various investments in patient safety. Yet, predicating safety efforts on the mistaken belief in a short-term return on investments will stall patient safety efforts.

Dietary supplement use in pediatric patients with cystic fibrosis.

PURPOSE: The use of dietary supplements and their perceived effectiveness in pediatric patients with cystic fibrosis (CF) were studied. METHODS: A descriptive survey, comprising both open- and closed-ended questions, was developed to assess current and past use of dietary supplements, identify sources of dietary supplement information, determine the perceived effectiveness of these dietary supplements, and evaluate families' knowledge of regulations regarding dietary supplements. RESULTS: A total of 121 pediatric CF patients and their families completed the survey. Assessment of dietary supplement use showed that 19% of patients (n = 23) were currently using dietary supplements and 10% (n = 12) reported past dietary supplement use. A total of 5 patients reported both current and past use of dietary supplements. Almost 40% of the patients who reported dietary supplement use did not inform their primary care provider about their use. While many factors may influence a patient's decision to begin therapy with a dietary supplement, 20% (n = 6) of patients felt their physician was most influential. Most patients (n = 104, 86%) correctly believed that dietary supplements are not regulated in the same manner as other prescription medications; however, only 60% (n = 72) would change the way dietary supplements are regulated. CONCLUSION: The use of dietary supplements in pediatric patients with CF was common, although few patients and families perceived it as effective for treating CF.

Variants in mannose-binding lectin and tumour necrosis factor alpha affect survival in cystic fibrosis.

BACKGROUND: Patients with cystic fibrosis with the same mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene differ widely in survival suggesting other factors have a substantial role in mortality. OBJECTIVE: To determine if the genotype distribution of variants in three putative cystic fibrosis modifier genes (tumour necrosis factor alpha (TNFalpha), transforming growth factor beta1 (TGFbeta1) or mannose-binding lectin (MBL2)) differed among patients with cystic fibrosis grouped according to age and survival status. METHODS: Genotypes of four variants (TNFalpha-238, TNFalpha-308, TGFbeta1-509 and MBL2 O) were determined in three groups of Caucasians from a single medical centre: 101 children with cystic fibrosis (aged <17 years; mean age 9.4 years), 115 adults with cystic fibrosis (aged > or =17 years; mean age 30.8 years) and 38 non-surviving adults with cystic fibrosis (21 deceased and 17 lung transplant after 17 years of age). Genotypes of 127 healthy Caucasians in the same geographical region were used as controls. Kaplan-Meier and Cox hazard regression were used to evaluate the genotype effect on cumulative survival. RESULTS: Genotype frequencies among adults and children with cystic fibrosis differed for TNFalpha-238 (G/G vs G/A; p = 0.022) and MBL2 (A/A vs O/O; p = 0.016). When adults with cystic fibrosis were compared to non-surviving adults with cystic fibrosis, genotype frequencies of both genes differed (TNFalpha-238G/G vs G/A; p = 0.0015 and MBL2: A/A vs O/O; p = 0.009). The hazard ratio for TNFalpha-238G/G vs G/A was 0.25 (95% CI 0.06 to 1.0, p = 0.04) and for MBL2 O/O vs A/A or A/O was 2.5 (95% CI 1.3 to 4.9, p = 0.007). CONCLUSIONS: TNFalpha-238 G/A and MBL2 O/O genotypes appear to be genetic modifiers of survival of cystic fibrosis.

Calcium kinetics are altered in clinically stable girls with cystic fibrosis.

Reduced bone mass in individuals with cystic fibrosis (CF) may result from alterations in calcium metabolism. Bone calcium deposition and resorption rates, calcium balance, and markers of bone turnover were assessed using stable isotopes of calcium in 22 prepubertal and pubertal girls with CF. Bone calcium deposition was associated with the availability of dietary calcium, total serum osteocalcin, and leptin concentrations. Reduced bone mass in individuals with CF may result from inadequate bone calcium (Ca) deposition, and excessive resorption, although these parameters have not been directly assessed in children with CF. We used stable Ca isotopes to measure rates of bone Ca deposition (Vo+), resorption, and retention in 22 clinically stable girls with CF (aged 7-18 yr). Rates of bone Ca deposition were determined by mathematically modeling the disappearance of iv Ca stable isotope ((42)Ca) for 6 d post dosing. Indirect markers of bone turnover and hormones associated with pubertal development were also assessed. Rates of bone Ca deposition and retention were highest during early puberty (Tanner stages 2 and 3). Calcium deposition rates in prepubertal (Tanner 1) and postmenarchal girls (Tanner stages 4 and 5) did not support substantial bone Ca retention. Net absorption of dietary Ca and serum osteocalcin and leptin concentrations were positively associated with Vo+. Time post menarche and serum leptin concentrations explained 91% of the variability in Vo+ (P = 0.0007). Serum total osteocalcin was low (10.9 +/- 5.4 ng/ml), and a substantial percentage of osteocalcin was undercarboxylated (54.3 +/- 11.8%). We concluded that increased calcium absorption and serum leptin concentrations were significantly associated with rates of bone Ca deposition, demonstrating an impact of nutritional status on this process. Rates of bone Ca deposition were lower than typically reported in healthy children, as were indirect markers of bone formation. These alterations in bone turnover contribute to reduced bone mass in girls with CF.

Senior executive adopt-a-work unit: a model for safety improvement.

BACKGROUND: At The Johns Hopkins Hospital (JHH), the patient safety committee created a safety program that focused on encouraging staff in selected units to identify and eliminate potential errors in the patient care environment. As part of this program, senior hospital executives each adopted an intensive care unit and worked with the unit staff to identify issues and to empower staff to address safety issues. JHH PATIENT SAFETY PROGRAM: The program consisted of eight steps, which together require six months for implementation: (1) conduct a culture survey; (2) educate staff on the science of safety; (3) identify staff safety concerns through a staff safety survey; (4) implement the senior executive adopt-a-work unit program; (5) implement improvements; (6-7) document results, share stories, and disseminate results; and (8) resurvey staff. RESULTS: The senior executive adopt-a-work unit program was successful in identifying and eliminating hazards to patient safety and in creating a culture of safety. DISCUSSION: The program can be broadly implemented. The keys to program success are the active role of an executive advocate and staff's willingness to openly discuss safety issues on the units. Regular meetings between the advocates and the units have provided a forum for enhancing executive awareness, increasing staff confidence and trust in executive involvement, and swiftly and effectively addressing areas of potential patient harm.

Gastric function in children with cystic fibrosis: effect of diet on gastric lipase levels and fat digestion.

The effect of diet, usual (44 +/- 4% energy as fat), high-fat (49 +/- 4% energy as fat), and moderate-fat (33 +/- 2% energy as fat), on gastric function (lipase and pepsin activities, pH, emptying rate) and intragastric digestion of fat were assessed in six children with cystic fibrosis. Fasting and postprandial activity of digestive enzymes, gastric pH, and gastric volume measured before, during, and after 120 min of feeding did not differ significantly as a function of fat intake. Postprandial gastric lipase output (units per kilogram of body weight) during usual, moderate-fat, and high-fat diets was close to or higher than (38.8 +/- 7.2, 44.9 +/- 8.6, and 54.8 +/- 5.5 U/kg per 20 min) gastric lipase output of premature infants (22.5 +/- 6.4 to 28.3 +/- 6.6 U/kg per 20 min) or of healthy adults (5.4 +/- 0.4 U/kg per 15 min) fed a high-fat diet. Postprandial pepsin output was higher (4749 +/- 797, 6117 +/- 925, and 5444 +/- 819 U/kg per 20 min) than in premature infants (597 +/- 77 to 743 +/- 97 U/kg per 20 min) or healthy adults (781 +/- 56 U/kg per 15 min). Eighty minutes after feeding gastric lipolysis reached 20 to 36%. This study shows that gastric lipase activity is high in cystic fibrosis patients maintained on diets providing 32% to 49% energy as fat, and that gastric lipase level did not increase over the ranges of dietary fat intake tested.

Endogenous fecal losses of calcium compromise calcium balance in pancreatic-insufficient girls with cystic fibrosis.

OBJECTIVE: Bone mineral density is compromised in individuals with cystic fibrosis (CF); calcium is the major bone mineral. This study examined the impact of endogenous fecal calcium (V(endo)) losses on calcium balance in girls with CF. Study design V(endo) was measured in 12 girls with CF (aged 7-18 years): 7 younger, premenarcheal girls with compromised nutritional status; and 5 older, postmenarcheal girls with adequate nutritional status. V(endo) was measured as the amount of intravenously administered (42)Ca, a calcium stable isotope, in stool relative to urine over 6 days. V(endo) was compared between pre- and postmenarcheal girls by Student's t test. Actual calcium balance [absorbed calcium-(urinary calcium (V(u))+V(endo))] was compared with estimated balance (assuming V(endo)=1.6 mg/kg/day calcium) by paired t test. RESULTS: V(endo) was 99.3+/-42.3 mg/day. By body weight, V(endo) was highest among premenarcheal girls (3.37+/-1.09 mg/kg/day), resulting in excess losses (>1.6 mg/kg/day) of 55.0+/-45.7 mg/day. Over 1 year, this represents 20.1+/-16.7 g of unattained bone calcium or 6.7+/-4.2% of the bone calcium content of these girls. CONCLUSIONS: V(endo) is a significant source of calcium loss in individuals with CF and may limit calcium availability for bone mineral deposition.

Efficiency of calcium absorption is not compromised in clinically stable prepubertal and pubertal girls with cystic fibrosis.

BACKGROUND: Reduced bone mass is common in both children and adults with cystic fibrosis (CF) and may be a consequence of inadequate calcium absorption. The effect of CF on intestinal calcium absorption and retention has not been described in children. OBJECTIVE: Calcium absorption and urinary losses were characterized in clinically stable girls with CF consuming self-selected diets and following usual pancreatic enzyme regimens. DESIGN: The percentage of calcium absorption was assessed in 23 girls (aged 7-18 y) with CF by using oral ((44)Ca) and intravenous ((42)Ca) stable isotopes. Girls were grouped according to Tanner stage of breast development. True calcium absorption (V(a)) was determined as the product of percentage calcium absorption and average 4-d daily calcium intake. Calcium balance was estimated by subtracting urinary calcium and estimated endogenous fecal losses from the measure of V(a). Analysis of variance was used to compare outcomes among pubertal groups, and regression analysis was used to describe the relations of percentage and total calcium absorption to calcium intake and of urinary calcium to sodium excretion. RESULTS: Percentage calcium absorption was inversely related to calcium intake. Percentage absorption and V(a) were similar to values observed in healthy girls in other studies. Total calcium absorption and estimated calcium balance were significantly greater among girls in early puberty (Tanner stages 2-3) than in prepubertal or late-pubertal girls (P < 0.05). Urinary calcium was positively related to urinary sodium excretion (P = 0.02). CONCLUSION: The efficiency of calcium absorption was not compromised in clinically stable girls with CF.

Ciprofloxacin-induced renal insufficiency in cystic fibrosis.

Acute renal insufficiency is known to occur in patients who are taking ciprofloxacin, particularly the elderly. We report two young patients with cystic fibrosis who presented with acute renal insufficiency after 2-3 weeks of oral ciprofloxacin therapy. The incidence of this adverse effect in children and young adults who have cystic fibrosis is unknown. Multiple mechanisms for ciprofloxacin-induced nephrotoxicity have been proposed.