Annick Lavoie

Treatment of Aspergillus fumigatus in Patients with Cystic Fibrosis: A Randomized, Placebo-Controlled Pilot Study

Background Many patients with cystic fibrosis develop persistent airway infection/colonization with Aspergillus fumigatus, however the impact of A. fumigatus on clinical outcomes remains unclear. The objective of this study was to determine whether treatment directed against Aspergillus fumigatus improves pulmonary function and clinical outcomes in patients with cystic fibrosis (CF). Methods We performed a double-blind randomized placebo-controlled pilot clinical trial involving 35 patients with CF whose sputum cultures were chronically positive for A. fumigatus. Participants were centrally randomized to receive either oral itraconazole 5 mg/kg/d (N = 18) or placebo (N = 17) for 24 weeks. The primary outcome was the proportion of patients who experienced a respiratory exacerbation requiring intravenous antibiotics over the 24 week treatment period. Secondary outcomes included changes in FEV1 and quality of life. Results Over the 24 week treatment period, 4 of 18 (22%) patients randomized to itraconazole experienced a respiratory exacerbation requiring intravenous antibiotics, compared to 5 of 16 (31%) placebo treated patients, P = 0.70. FEV1 declined by 4.62% over 24 weeks in the patients randomized to itraconazole, compared to a 0.32% improvement in the placebo group (between group difference = −4.94%, 95% CI: −15.33 to 5.45, P = 0.34). Quality of life did not differ between the 2 treatment groups throughout the study. Therapeutic itraconazole blood levels were not achieved in 43% of patients randomized to itraconazole. Conclusion We did not identify clinical benefit from itraconazole treatment for CF patients whose sputum was chronically colonized with A. fumigatus. Limitations of this pilot study were its small sample size, and failure to achieve therapeutic levels of itraconazole in many patients. Trial Registration ClinicalTrials.gov NCT00528190

Brain maturity in regard to the auditory brainstem response in small-for-date neonates

The auditory brainstem response has been used in neonates at risk of hearing impairment or as a functional measurement of brain maturity. The goal of the present study was to evaluate the auditory brainstem response in small-for-date newborns, in relation to changes observed with fetal maturity in a control group. Compared to controls with similar maturity, a significant delay for the appearance of waves III and V, and between waves I-V was observed in the small-for-date newborns, suggesting an alteration of the auditory pathway within the brainstem rather than an impairment of the peripheral auditive apparatus. Indeed, small-for-date newborns reacted to the test in a similar manner as premature babies in whom such a delay was also observed. Our data would suggest a functional brain immaturity in small-for-date newborns, during the first days of life, in regard to the auditive evoked potential, which may be related to some alterations in brain development reported with fetal malnutrition.

Dichotomy between postprandial glucose and lipid profiles in adults with cystic fibrosis: A pilot study

BACKGROUND Cystic fibrosis (CF) patients present a high incidence of glucose tolerance abnormalities. Altered insulin secretion combined with recommended high-fat intake could be associated with dysregulation of glucose and lipid metabolism. We examined postprandial glucose and lipid profiles during an oral glucose tolerance test (OGTT) and following a standardized high-fat test meal (TM). METHODS Sixteen CF patients with normal glucose tolerance (NGT) or CF-related diabetes (CFRD) and 16 controls underwent a 4 h OGTT and a TM. We then measured plasma glucose, insulin, free fatty acid (FFA) and triglyceride (TG) concentrations. RESULTS CF patients presented higher glucose excursion compared to controls after the OGTT and TM. However, in CF patients, this excursion was significantly reduced in both amplitude and length after the TM. The TM provoked a comparable increase in TG levels in both groups whereas they remained stable during the OGTT. FFAs were suppressed similarly in both groups after both challenges. CONCLUSION CF is associated with abnormal glucose excursion in the presence of relatively normal lipid excursion. The rapid normalization of glucose values after a mixed meal should be further explored and, if confirmed, might have significant implications for CFRD diagnostic.

Pericardial Fat Necrosis Presenting as Acute Pleuritic Chest Pain

A 58-year-old man presented to the Emergency Department with a 4-day history of acute and progressive left pleuritic chest pain. The chest pain appeared suddenly, awakening the patient in the middle of the night. There was no history of trauma or associated dyspnea. Pain was not entirely relieved by non-steroidal anti-inflammatory drugs (NSAIDS). Prior medical history was relevant for diabetes, hypertension, and dyslipidemia. There were no risk factors for pulmonary embolus. On examination, the patient was cooperative and alert. Vitals signs were normal. Physical examination revealed decreased air entry in the left lower lung. Calves were non-tender and not swollen. The initial chest X-ray study showed a rise of the left hemidiaphragm and small left pleural effusion (Figure 1). Laboratory values were normal, with negative cardiac enzyme levels and D-dimers. The electrocardiogram (ECG) showed a normal sinus rhythm with a right bundle branch block, the exact same result as an ECG done 5 years prior (Figure 2). The patient’s pain was relieved by morphine. Probability for pulmonary embolus was intermediate at ventilation-perfusion scintigraphy, which demonstrated a ventilation-perfusion mismatch in the lateral basal segment of the left lower lobe. Intravenous heparin was started. Due to the result of lung scintigraphy, a pulmonary computed tomography (CT) angiography was requested. CT angiography did not show any signs of pulmonary embolism, although distal vascular evaluation at both lung bases was limited due to respiratory artifacts.

Association between glucose intolerance and bacterial colonisation in an adult population with cystic fibrosis, emergence of Stenotrophomonas maltophilia

BACKGROUND Diabetes is common in cystic fibrosis (CF). Glucose can be detected in the airway when the blood glucose is elevated, which favours bacterial growth. We investigated the relationship between dysglycemia and lung pathogens in CF. METHODS Cross-sectional and prospective analysis of CF patients (N=260) who underwent a 2h-oral glucose tolerance test. Clinical data was collected. RESULTS Stenotrophomonas maltophilia (S. maltophilia) was the sole bacteria increased in dysglycemic (AGT: 20.2%, CFRD: 21.6%) patients compared to normotolerants (NGT: 8.7%). S. maltophilia positive patients with dysglycemia had more pulmonary exacerbation events compared to NGTs (1.22 vs 0.63, P=0.003). The interaction between S. maltophilia colonisation and glucose tolerance status significantly increases the risk of lower lung function (P=0.003). Its growth was not affected by the evolution of the glucose tolerance after three years follow-up. CONCLUSION Prevalence of S. maltophilia was higher in dysglycemic patients, supporting the idea that S. maltophilia is a marker of disease severity in CF.

“One Size Fits all in the Global Marketing Classroom…Not Really” Impact of Students’ National Culture and Acculturation Levels

Student ratings of instructors have received considerable attention in academia due to their use in annual reviews, promotion and tenure decisions, and course assignments. As a result, instructors (for better or worse) often contemplate utilizing various tactics and strategies that might increase student satisfaction. While personal characteristics of the instructor (e.g. enthusiasm) are undoubtedly related to student ratings, the research in this area suggests that all instructors, regardless of personal characteristics, can enhance student satisfaction through various structural mechanisms, such as improved course design or influence tactics, hence developing their teaching style.

208 Long-term and seasonal impact of a vitamin D3 (cholecalciferol) supplementation protocol on vitamin D [25(OH)D] serum levels among cystic fibrosis adults in a Montreal clinic

Vitamin D deficiency is a widely reported problem in patients with Cystic Fibrosis (CF). Objectives To analyse the long term and seasonal impact on vitamin D [25(OH)D] serum levels of our vitamin D3 protocol. Methods A retrospective study was performed in our CF adult clinic. Data for 200 patients were obtained from their medical files for 2009, and compared to their own latest data available (2013–2014). Protocol Total starting D3 prescribed dose was 2800 IU/day during the summer months (May to October), 4400 IU/day during the winter months (November to April) or the weekly dose equivalent. Results Population studied: 55% male/45% female, age 34.4±8.3 years, FEV1% 65.1±21.4, BMI 23.2±3.5 kg/m 2 , 85.5% with pancreatic insufficiency. Mean 25(OH)D serum levels were significantly superior after the protocol (64.7±25.6 nmol/L vs 92.3±28.4 nmol/L, p TableLong-term impact of D3 Protocol25(OH)D serum level adequacyProportion of patientsBefore D3 ProtocolAfter D3 ProtocolDeficient, 150 nmo1/L0.5%3% Before the protocol, patients showed significant seasonal variation in 25(OH)D serum levels with lower levels in winter months compared to summer months (58.6±28.6 nmol/L vs 69.6±21.7 nmol/L, p Conclusion This study suggests that a vitamin D3 supplementation protocol with higher doses during winter months was efficient for the long term and seasonal management of vitamin D deficiency in our Montreal adult CF clinic.

WS13.4 Vitamin D levels among CF adults compared to general adult population in Canada

Introduction: The FDA recently issued a broad safety communication regarding the possible increased risk of osteoporosis-related bone fracture with the use of PPI’s. PPI’s are regularly used in CF for treatment of GORD and to help with the efficiency of PERT. And as osteoporosis is a co-morbidity of CF we aimed to assess if there was any relationship between PPI and bone density in children with CF. Methods: A retrospective review of PPI usage and dxa scans was conducted. Sixtyfour children with mean age of 11 (1.8 SD) were included in study. PPI usage and duration was recorded. Dxa scans were carried out on the Lunar DPXL-PED. Bone mineral density (BMD) was recorded and bone mineral apparent density (BMAD) was calculated. FEV1 was also recorded. Minitab Statistical Package was used to analyse the data. Results: Twenty-two (35%) of children were on PPI’s. Duration of use ranged from 1 to 4 years. PPI usage had a marginally significant negative effect on BMD [Z score mean of −0.31 (no PPI) and −0.94 (on PPI), p = 0.05]. PPI had no effect on BMAD [z score of 0.17 (no PPI) and −0.37 (on PPI), p = 0.08]. The duration of PPI had no influence on BMD or BMAD (p = 0.71 and p = 0.51). There was no difference in FEV1 between the two groups (means of 75% and 76%, p = 0.84). Conclusion: PPI’s may be prescribed more frequently in sicker patients and thus could explain the marginal difference found between groups. However this is not the case here as FEV1 did not differ. Therefore further larger studies are needed in this area. In the meantime, clinicians should be aware of their potential risk when considering PPI therapy and should use the lowest effective dose and duration necessary.