Patient-partner engagement at the Centre de recherche du CHUS in the Province of Québec, Canada: from an intuitive methodology to outreach after three years of implementation.

BACKGROUND: Medical societies and funding agencies strongly recommend that patients be included as partners in research publications and grant applications. Although this "top-down" approach is certainly efficient at forcing this new and desirable type of collaboration, our past experience demonstrated that it often results in an ambiguous relationship as not yet well integrated into the cultures of either patients' or the researchers'. The question our group raised from this observation was: "How to generate a cultural shift toward a fruitful and long-lasting collaboration between patients and researchers? A "bottom-up" approach was key to our stakeholders. The overall objective was to build a trusting and bidirectional-ecosystem between patients and researchers. The specific objectives were to document: 1) the steps that led to the development of the first patient-partner strategic committee within a research center in the Province of Québec; 2) the committee's achievements after 3 years. METHODS: Eighteen volunteer members, 12 patient-partners and 6 clinician/institutional representatives, were invited to represent the six research themes of the Centre de recherche du CHU de Sherbrooke (CRCHUS) (Quebec, Canada). Information on the services offered by Committee was disseminated internally and to external partners. Committee members satisfaction was evaluated. RESULTS: From May 2017 to April 2020, members attended 29 scheduled and 6 ad hoc meetings and contributed to activities requiring over 1000 h of volunteer time in 2018-2019 and 1907 h in the 2019-2020 period. The Committee's implication spanned governance, expertise, and knowledge transfer in research. Participation in these activities increased annually at local, provincial, national and international levels. The Patient-Partner Committee collaborated with various local (n = 7), provincial (n = 6) and national (n = 4) partners. Member satisfaction with the Committee's mandate and format was 100%. CONCLUSIONS: The CRCHUS co-constructed a Patient-Partner Strategic Committee which resulted in meaningful bilateral, trusting and fruitful collaborations between patients, researchers and partners. The "bottom-up" approach - envisioned and implemented by the Committee, where the expertise and the needs of patients complemented those of researchers, foundations, networks and decision-makers - is key to the success of a cultural shift. The CRCHUS Committee created a hub to develop the relevant intrinsic potential aimed at changing the socio-cultural environment of science.

Beneficial Effects of Regular Physical Activity on Exercise-Induced Analgesia in Adolescent Males.

PURPOSE: To evaluate exercise-induced analgesia (EIA) effectiveness in healthy adolescent males and to investigate possible associations between EIA and physiological/psychological variables. METHODS: Twenty-eight healthy adolescent males (14-17 y) participated in this study. EIA was evaluated by comparing perceptions of heat pain stimulations before and after an increasing maximal load test on a cycle ergometer (VO2max). RESULTS: Pain intensity for mild and strong heat pain stimulations significantly decreased following physical exercise (mild: EIA = 28.6%; 95% confidence interval, 0.9-1.9; P < .001 and strong: EIA = 11.3%; 95% confidence interval, 0.3-1.4; P = .002). The number of physical activity hours per week was positively correlated with the effectiveness of EIA for mild and strong pain intensity (r = .41, P = .03 and r = .43, P = .02, respectively). CONCLUSIONS: Intense physical exercise decreases perception of intensity of experimental heat pain in healthy adolescent males. The least physically active adolescents have reduced EIA effectiveness to experimental heat pain stimulations compared with physically active ones. Adolescents adopting an active lifestyle have more endogenous pain inhibition and could, therefore, potentially be less disposed to suffer from chronic pain later in life.

Determination of peak cardiorespiratory fitness parameters in children: which averaging method should we use?

The purpose of this study was to identify which averaging methods most accurately measures peak cardiorespiratory fitness (CRF) parameters [peak O2 uptake (VO2), peak O2pulse and peak respiratory exchange ratio (RER)] in a sample of healthy children and adolescents. In this cross-sectional multicenter study, we recruited 278 healthy children aged 12-17 years. We compared the mean peak value of three CRF parameters using the recommended averaging methods (30-second block average) with alternative averaging methods such as moving averages or shorter smoothing periods. We also assessed averaging methods for accuracy by individually reviewing breath-by-breath scatter plots. The 30-second block average method resulted in a lower mean peak VO2 and in an increased proportion of underestimated peak values. Using a 30-second moving average significantly increased mean peak values which increased accuracy. Similar results were found for peak RER and peak O2pulse. In conclusion, the currently recommended averaging method (30-second block average) increased the risk of misinterpretation of peak CRF values in children. Using a moving average approach decreased misinterpretation and increased accuracy.

Reduced endogenous pain inhibition in adolescent girls with chronic pain.

Background and aims Chronic pain is affecting a growing number of individuals including adolescents. Different endogenous pain inhibitory systems could confer protection against development of chronic pain. Decreased pain perception can be observed following intense pain (i.e. conditioned pain modulation - CPM) or after physical exercise (i.e. exercise-induced analgesia - EIA). Reduced effectiveness of pain inhibitory mechanisms have been reported in several chronic pain conditions. However, the extent of these dysfunctions has not been thoroughly investigated in adolescents suffering from chronic pain. Our hypothesis was that adolescents suffering from chronic pain have less effective CPM and EIA than pain-free teenagers. Methods Twenty-five healthy adolescent girls and 16 teenage girls with chronic pain participated in this study. Only girls were included in this investigation, since chronic pain is more prevalent in females. The effectiveness of CPM was assessed by comparing heat pain stimulations (individually adapted to induce mild pain intensity) performed with a thermode before and after a cold pressor test (CPT; 2 min, 10 °C). EIA was evaluated by comparing pain intensity produced by an ice cube placed on the forearm before and after a graded exercise test on a cycle ergometer. Results Pain intensity produced by heat pain stimulations decreased following CPT in healthy (p<0.05), but not in chronic pain adolescent girls (p=0.4). Pain intensity induced by the ice cube was reduced after exercise in healthy (p<0.05), but not in chronic pain adolescents (p=0.9). The effectiveness of CPM and EIA was inferior in teenage girls suffering from chronic pain compared to healthy participants (p<0.05). Conclusions Endogenous pain inhibitory mechanisms triggered by intense pain or by physical exercise are effective in healthy adolescent girls. Teenage girls living with chronic pain do not show diminished pain perception after a CPT or a graded exercise test. These results suggest that pain inhibitory mechanisms such as CPM and EIA are ineffective in adolescent girls suffering from chronic pain. Implications In a wider context, the findings of the present research could help understand better the mechanisms involved in the development of chronic pain. Improved comprehension of this subject might help prevent chronic pain conditions and thus, reduce the negative impacts of this burden.

New Reference Values for Cardiopulmonary Exercise Testing in Children.

INTRODUCTION: Cardiopulmonary exercise testing is an essential tool to assess cardiorespiratory fitness (CRF) in children. There is a paucity of adequate pediatric reference values that are independent of body size and pubertal stage. The purpose of this study is to provide Z score equations for several maximal and submaximal CRF parameters derived from a prospectively recruited sample of healthy children. METHODS: In this cross-sectional multicenter study, we prospectively recruited 228 healthy children 12 to 17 yr old in local schools. We performed a symptom-limited cardiopulmonary exercise testing progressive ramp protocol on an electronically braked cycle ergometer. Eighteen CRF parameters were analyzed. We tested several regression models to obtain prediction curves that minimized residual association with age, body size, and pubertal stage. Both the predicted mean and the predicted SD were modeled to account for heteroscedasticity. RESULTS: We identified nonlinear association of CRF parameters with body size and significant heteroscedasticity. To normalize CRF parameters, the use of a single body size variable was not sufficient. We therefore used multivariable models with various combination of height, corrected body mass, and age. Final prediction models yielded adjusted CRF parameters that were independent of age, sex, body mass, height, body mass index, and Tanner stages. CONCLUSIONS: We present Z score equations for several CRF parameters derived from a healthy pediatric population. These reference values provide updated predicted means and range of normality that are independent of sex and body size. Further testing is needed to assess if these reference values increase sensitivity and specificity to identify abnormal cardiorespiratory response in children with chronic diseases.

A Systematic Review of Reference Values in Pediatric Cardiopulmonary Exercise Testing.

Cardiopulmonary exercise testing (CPET) is used for the diagnosis and prognosis of cardiovascular and pulmonary conditions in children and adolescents. Several authors have published reference values for pediatric CPET, but evaluation of their validity is lacking. The aim of this study was to review pediatric CPET references values published between 1980 and 2014. We specifically assessed the adequacy of the normalization methods used to adjust for body size. Articles that proposed references values were reviewed. We abstracted information on exercise protocols, CPET measurements and normalization methods. We then evaluated the studies' methodological quality and assessed them for potential biases. Thirty-four studies were included. We found important heterogeneity in the choice of exercise protocols and in the approach to adjustment for body size or other relevant confounding factors. Adjustment for body size was principally done using linear regression for age or weight. Assessment of potential biases (residual association, heteroscedasticity and departure from the normal distribution) was mentioned in only a minority of studies. Our study shows that contemporary pediatric reference values for CPET have been developed based on heterogeneous exercise protocols and variable normalization strategies. Furthermore, assessment of potential bias has been inconsistent and insufficiently described. High-quality reference values with adequate adjustment for confounding variables are needed in order to optimize CPET's specificity and sensitivity to detect abnormal cardiopulmonary response to exercise.

Staphylococcus aureus with decreased susceptibility to glycopeptides in cystic fibrosis patients.

We report the isolation of Staphylococcus aureus with decreased susceptibility to glycopeptides in five CF patients and review the clinical and microbiological features of these cases. Three patients presented with pulmonary exacerbation that may be attributed to these strains and two of them were successfully treated using linezolid therapy. Glycopeptide-intermediate S. aureus (GISA) strains isolated in two patients were susceptible to methicillin, while the three other patients harbored methicillin-resistant GISA. Rarely reported in CF, GISA may remain underestimated due to the difficulty of detection, and both clinicians and microbiologists should be aware of the GISA emergence in CF patients' population.

Gluconobacter as well as Asaia species, newly emerging opportunistic human pathogens among acetic acid bacteria.

Acetic acid bacteria (AAB) are broadly used in industrial food processing. Among them, members of the genera Asaia, Acetobacter, and Granulibacter were recently reported to be human opportunistic pathogens. We isolated AAB from clinical samples from three patients and describe here the clinical and bacteriological features of these cases. We report for the first time (i) the isolation of a Gluconobacter sp. from human clinical samples; (ii) the successive isolation of different AAB, i.e., an Asaia sp. and two unrelated Gluconobacter spp., from a cystic fibrosis patient; and (iii) persistent colonization of the respiratory tract by a Gluconobacter sp. in this patient. We reviewed the main clinical features associated with AAB isolation identified in the 10 documented reports currently available in the literature. Albeit rare, infections as well as colonization with AAB are increasingly reported in patients with underlying chronic diseases and/or indwelling devices. Clinicians as well as medical microbiologists should be aware of these unusual opportunistic pathogens, which are difficult to detect during standard medical microbiological investigations and which are multiresistant to antimicrobial agents. Molecular methods are required for identification of genera of AAB, but the results may remain inconclusive for identification to the species level.

Characteristics of disorders associated with genetic mutations of surfactant protein C.

STUDY OBJECTIVES: To present diagnosis and treatment modalities of children with interstitial lung disease associated with frequent or rare surfactant protein C gene (SFTPC) mutation. PATIENTS: Twenty-two children with chronic lung disease associated with SFTPC mutation in a heterozygous form. RESULTS: Mutations located in the BRICHOS domain ('BRICHOS domain' group) were identified in six children, whereas 16 children carried mutations located outside the BRICHOS domain ('non-BRICHOS domain' group). The median age of onset was 3 (0-24) months. Four patients had neonatal respiratory distress, and symptom onset was associated with acute bronchiolitis in nine patients. Cough, tachypnoea and failure to thrive were initially noticed in all the children. Physical examination at presentation revealed tachypnoea (n=22), clubbing (n=1) and crackles (n=5). Low oxygen saturation (<95%) was observed in 18 patients. The predominant findings on initial high-resolution CT (HRCT) scans were basal-predominant ground-glass opacity (n=21) and cystic spaces (n=3). Bronchoalveolar lavage fluid (BALF) cell counts showed 379+/-56x10(3) cells/ml with increased neutrophil percentage (18+/-4%) independent of the mutation status. The median follow-up was 3.2 (1-18.3) years. Eighteen patients were treated by monthly methylprednisolone pulses associated with oral prednisolone (n=16), hydroxychloroquine (n=11) and/or azithromycin (n=4). Fifteen patients benefited from enteral nutrition. CONCLUSION: Initial diagnosis is based on clinical presentation, radiological features and BALF analysis, but the definitive diagnosis requires genetic analysis. Although progressive improvement was seen in most patients, the development of new therapeutic strategies with minimal side effects is needed.

NKX2-1 mutations leading to surfactant protein promoter dysregulation cause interstitial lung disease in "Brain-Lung-Thyroid Syndrome".

NKX2-1 (NK2 homeobox 1) is a critical regulator of transcription for the surfactant protein (SP)-B and -C genes (SFTPB and SFTPC, respectively). We identified and functionally characterized two new de novo NKX2-1 mutations c.493C>T (p.R165W) and c.786_787del2 (p.L263fs) in infants with closely similar severe interstitial lung disease (ILD), hypotonia, and congenital hypothyroidism. Functional analyses using A549 and HeLa cells revealed that NKX2-1-p.L263fs induced neither SFTPB nor SFTPC promoter activation and had a dominant negative effect on wild-type (WT) NKX2-1. In contrast,NKX2-1-p.R165W activated SFTPC, to a significantly greater extent than did WTNKX2-1, while SFTPB activation was only significantly reduced in HeLa cells. In accordance with our in vitro data, we found decreased amounts of SP-B and SP-C by western blot in bronchoalveolar lavage fluid (patient with p.L263fs) and features of altered surfactant protein metabolism on lung histology (patient with NKX2-1-p.R165W). In conclusion, ILD in patients with NKX2-1 mutations was associated with altered surfactant protein metabolism, and both gain and loss of function of the mutated NKX2-1 genes on surfactant protein promoters were associated with ILD in "Brain-Lung-Thyroid syndrome".

Thoracoscopy in pediatric pleural empyema: a prospective study of prognostic factors.

PURPOSE: The indications for thoracoscopy remain imprecise in cases of pleural empyema. This study aimed to identify preoperative prognostic factors to help in the surgical decision. METHODS: From 1996 to 2004, 50 children with parapneumonic pleural empyema underwent thoracoscopy either as the initial procedure (n = 26) or after failure of medical treatment (n = 24). Using multivariate analysis, we tested the prognostic value of clinical and bacteriological data, the ultrasonographic staging of empyema, and the delay before surgery. Outcome measures were technical difficulties, postoperative complications, time to apyrexia, duration of drainage, and length of hospitalization. RESULTS: The clinical and bacterial data did not significantly predict the postoperative course. Echogenicity and the presence of pleural loculations at ultrasonography were not independent significant prognostic factors. A delay between diagnosis and surgery of more than 4 days was significantly correlated (P < .05) with more frequent surgical difficulties, longer operative time, more postoperative fever, longer drainage time, longer hospitalization, and more postoperative complications, such as bronchopleural fistula, empyema relapse, and persistent atelectasia. CONCLUSION: The main prognostic factor for thoracoscopic treatment of pleural empyema is the interval between diagnosis and surgery. A 4-day limit, corresponding to the natural process of empyema organization, is significant. The assessment of loculations by ultrasonography alone is not sufficient to predict the postoperative course.

Clinical effects of heliox administration for acute bronchiolitis in young infants.

OBJECTIVE: To assess the effect of heliox, a helium-oxygen mixture, on respiratory distress symptoms in young infants. DESIGN: Prospective, randomized, double-blind study. SETTING: Pediatric ICU (PICU) of a university hospital. PATIENTS: Twenty infants, all < 3 months old, admitted to the PICU with moderate-to-severe acute respiratory syncytial virus bronchiolitis. INTERVENTIONS: All infants were randomly and blindly assigned to inhale either heliox or an air-oxygen mixture (airox) for 1 h under an oxyhood. MEASUREMENTS AND RESULTS: After 1 h, the respiratory distress score was significantly lower in the heliox group compared with the airox group (3.05 vs 5.5, p < 0.01), with a significant reduction in accessory muscles use (p < 0.05) and expiratory wheezing (p < 0.01). In contrast, inspiratory breath sounds and cyanosis did not significantly differ between groups. The ex-premature infants of the heliox group had a higher respiratory distress score at baseline compared with the term infants of this group (5.8 vs 5.2, p < 0.05) and a comparable decrease in the score at 60 min. CONCLUSIONS: In young infants, even those born prematurely, heliox breathing induced a rapid reduction in accessory muscles use and expiratory wheezing. Further studies are needed to confirm the decreased respiratory muscle work of breathing during heliox inhalation in this population.

Clinical and microbiological features of Inquilinus sp. isolates from five patients with cystic fibrosis.

Patients with cystic fibrosis (CF) may be colonized with unusual gram-negative bacilli whose identification is difficult and clinical impact unclear. We describe the clinical and microbiological features of five colonizations with organisms belonging to the recently described genus Inquilinus in CF patients. Isolates were identified from Burkholderia cepacia selective medium by means of 16S rRNA analysis. All of them were resistant to colistin, penicillins, cephalosporins, and monobactams but exhibited a remarkable susceptibility to imipenem. One of the five patients was transiently colonized with a nonmucoid isolate, whereas the four other patients were persistently colonized over the period of follow-up (8 to 21 months) with mucoid isolates. Pulsed-field gel electrophoresis of SpeI-digested genomic DNA was powerful for strain genotyping and demonstrated the clonality of Inquilinus sp. colonization for the two patients tested. Clinical evolution after the onset of Inquilinus was heterogeneous, but for at least one patient the lung function worsened and eradication of Inquilinus sp. was unsuccessful despite several imipenem courses. Finally, Inquilinus spp. may represent a new threat for CF patients due to their mucoid characteristic, their multiresistant pattern to antibiotics, and their ability to persist in the respiratory tract.

Training of aerobic and anaerobic fitness in children with asthma.

OBJECTIVE: To assess the effect of a training protocol on aerobic and anaerobic fitness in children with asthma. STUDY DESIGN: Sixteen boys (mean age: 13 years; range: 10-16 years) with mild-to-moderate asthma participated in a rehabilitation program that included 6 weeks of individualized training on a cycle ergometer. Two groups were randomly formed: the control group (CG, n = 7) and the training group (TG, n = 9), which exercised at an intensity set at the heart rate corresponding to the ventilatory threshold, with 1-minute sprints against the maximal aerobic power (MAP) every 4 minutes. Session duration was 45 minutes, 3 sessions per week. Changes in maximal oxygen uptake (VO(2)max), MAP, short-term peak power (PP), and pulmonary function were assessed. RESULTS: Two patients of the training group did not complete the study. Pulmonary function remained unchanged in both groups. Improvement in both aerobic and anaerobic fitness was significant only in the training group (TG vs CG): VO(2)max +18% +/- 2.1% versus +9% +/- 4.5% (P <.05), MAP +32% +/- 5% versus 12% +/- 7% (P <.05), PP +21% +/- 5.7% versus +8.8% +/- 10% (P <.01). CONCLUSION: Exercise training with high-intensity bouts is well tolerated in children with mild-to-moderate asthma. When included in a global rehabilitation program, this type of training improves both aerobic and anaerobic fitness. Anaerobic activities should be considered in sports rehabilitation programs for children with asthma.