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IntroductionVentilator-associated pneumonia (VAP) is a common healthcare-associated infection in the intensive care unit (ICU). Probiotics are defined as live microorganisms that may confer health benefits when ingested. Prior randomised trials suggest that probiotics may prevent infections such as VAP and Clostridioides difficile–associated diarrhoea (CDAD). PROSPECT (Probiotics to Prevent Severe Pneumonia and Endotracheal Colonization Trial) is a multicentre, double-blinded, randomised controlled trial comparing the efficacy of the probiotic Lactobacillus rhamnosus GG with usual care versus usual care without probiotics in preventing VAP and other clinically important outcomes in critically ill patients admitted to the ICU.Methods and analysisThe objective of E-PROSPECT is to determine the incremental cost-effectiveness of L. rhamnosus GG plus usual care versus usual care without probiotics in critically ill patients. E-PROSPECT will be performed from the public healthcare payer’s perspective over a time horizon from ICU admission to hospital discharge.We will determine probabilities of in-ICU and in-hospital events from all patients alongside PROSPECT. We will retrieve unit costs for each resource use item using jurisdiction-specific public databases, supplemented by individual site unit costs if such databases are unavailable. Direct costs will include medications, personnel costs, radiology/laboratory testing, operative/non-operative procedures and per-day hospital ‘hoteling’ costs not otherwise encompassed. The primary outcome is the incremental cost per VAP prevented between the two treatment groups. Other clinical events such as CDAD, antibiotic-associated diarrhoea and in-hospital mortality will be included as secondary outcomes. We will perform pre-specified subgroup analyses (medical/surgical/trauma; age; frailty status; antibiotic use; prevalent vs no prevalent pneumonia) and probabilistic sensitivity analyses for VAP, then generate confidence intervals using the non-parametric bootstrapping approach.Ethics and disseminationStudy approval for E-PROSPECT was granted by the Hamilton Integrated Research Ethics Board of McMaster University on 29 July 2019. Informed consent was obtained from the patient or substitute decision-maker in PROSPECT. The findings of this study will be published in peer-reviewed journals.Trial registration numberNCT01782755; Pre-results.

Leduc BE, Dagher JH, Mayer P, Bellemare F, Lepage Y. Estimated prevalence of obstructive sleep apnea–hypopnea syndrome after cervical cord injury. Objectives To estimate the prevalence of obstructive sleep apnea–hypopnea syndrome (OSAHS) in patients with cervical cord injury and to identify predictive factors. Design Cross-sectional study. Setting Rehabilitation center. Participants Forty-one adults with cervical cord injury of more than 6 months in duration. Interventions Medical history, physical exam, and full in home overnight polysomnography were undertaken. Data were collected on characteristics of spinal cord injury, current medication, sleeping habits, daytime sleepiness, body mass index (BMI), and neck circumference. Main Outcome Measure Presence or absence of OSAHS as defined by the American Academy of Sleep Medicine criteria (1999). Results Twenty-two (53%) patients (95% confidence interval [CI], 38.4%–68.9%) had OSAHS. Daytime sleepiness (odds ratio [OR], 41.1; 95% CI, 2.3–739.7; P =.02), BMI of 30kg/m 2 or higher (OR=17.2; 95% CI, 1.4–206.4; P =.03), and 3 or more awakenings during sleep (OR=34; 95% CI, 1.6–744.8; P =.03) were the best predictive factors of OSAHS obtained by a forward stepwise multiple logistic regression. Conclusions The estimated prevalence of OSAHS is high after cervical cord injury. OSAHS should be suspected, especially in patients with daytime sleepiness, obesity, and frequent awakenings during sleep.

In this paper, we describe a computational model dedicated to building an apnoea monitoring system for newborn babies. The proposed model is based on whole body plethysmography, which involves non-invasive measurement of lung ventilation indirectly from the pressure deflections generated when a subject breathes inside a chamber of fixed volume (Bert in C R Soc Biol Paris 20:22-23, 1868). The computational model simulates thermal and environmental flow conditions occurring in the neonate chamber, especially steady state flow with heat transfer and carbon dioxide (CO2) transport during the exhalation phase. This permits the variance of all critical parameters and the analysis of their effects on the distributions of interest. The main objective is to study thermal and air quality comfort conditions under which infants can be monitored for long-term periods. The method deploys computational fluid dynamics techniques and parametric modelling which, by allowing input parameters to be modulated, represent a more efficient and flexible analytical tool than previous experimental techniques. Simulation data reveal that the largest flow rates occur in areas near the openings with slight formation of air recirculation zones; temperature distribution shows signs of stratification, with higher temperatures than the supplied air, CO2 distribution presents acceptable air quality level and predicted mean vote index affords a relatively acceptable thermal comfort level. This analytical approach can be considered as innovative, and can find a new application in clinical infant apnoea monitoring in a way that allows determination of the optimal location for placing a sensor to detect respiration activity without any contact with the infant's body, and without any risk, in contrast to available whole body plethysmography techniques previously tested in infants (Fleming et al. in J Appl Physiol 55:1924-1931, 1983).

The volume of the rib cage is about 10% smaller in females than in males having the same height although the reason for this is presently unclear. The cranio-caudal inclination of ribs is greater in females than males but the length of ribs has not previously been compared between the sexes. In 23 males and 23 females studied at necropsy, body length, the length of the upper and lower limbs and the length of the thoracic spine were all smaller in females but the ratios of upper and lower limb lengths to body length and of thoracic spine length to body length were not different. By contrast, the lengths of the third, sixth and ninth ribs were not significantly different between males and females and the ratios of rib length to body length were all significantly greater in females. We conclude that in females the ribs grow longer in relation to the axial skeleton than in males.

The volume of adult female lungs is typically 10-12% smaller than that of males who have the same height and age. In this study, we investigated how this volume difference is distributed between the rib cage and the diaphragm abdomen compartments. Internal rib cage dimensions, diaphragm position relative to spine, and diaphragm length were compared in 21 normal male and 19 normal female subjects at three different lung volumes using anterior-posterior and lateral chest radiographs. At all lung volumes examined, females had smaller radial rib cage dimensions in relationship to height than males, a greater inclination of ribs, a comparable diaphragm dome position relative to the spine, and a shorter diaphragm length. Female subjects exhibited a greater inspiratory rib cage muscle contribution during resting breathing than males, presumably reflecting an improved mechanical advantage conferred to these muscles by the greater inclination of ribs. Because of a greater inclination of ribs, female rib cages could accommodate a greater volume expansion. The results suggest a disproportionate growth of the rib cage in females relative to the lung, which would be well suited to accommodate large abdominal volume displacements as in pregnancy.

Study objectives: To determine the effect of emphysema and lung volume reduction surgery (LVRS) on diaphragm length (Ldi) and its capacity to generate transdiaphragmatic pressure (Pdi). Design: Prospective clinical trial with a parallel group design. Setting: Laboratory investigations in normal volunteers recruited by advertisement and in emphysema outpatients being evaluated for elective LVRS. Study population: Thirteen normal subjects and 13 emphysema patients matched for age and sex. Six emphysema patients underwent LVRS. Measurements: Ldi and maximal Pdi during static inspiratory efforts (PdiMax) were measured at three different lung volumes (LVs). Pdi during maximal bilateral phrenic nerve twitch stimulation (PdiTw) was measured at functional residual capacity (FRC). All measurements were repeated at 3, 6, and 12 months postoperatively. Results: Ldi, PdiMax, and PdiTw were lower in emphysema patients than in normal subjects at their respective LVs. PdiMax and PdiTw at FRC returned within the normal range after LVRS in emphysema patients. The relationships between PdiMax and LV or Ldi were shifted respectively to higher LV and shorter Ldi in emphysema patients relative to normal subjects, both before and after LVRS. LVRS effected craniad displacement of the diaphragm but no change in rib cage dimensions. Improvements in dyspnea and quality of life after LVRS correlated with changes in LV and Ldi but not with changes in airway caliber. Conclusion: Adaptive mechanisms, consistent with sarcomere deletion, tend to restore diaphragm strength in emphysema patients at FRC, which are fully expressed after LVRS. Lung remodeling by LVRS may alter pleural surface pressure distribution, causing a sustained change in chest wall shape.

The time-frequency characteristics of muscular sounds (phonomyogram) produced by the contraction of the human diaphragm under various contractile states is evaluated with the cone-kernel distribution. The results show that the instantaneous frequency of the phonomyogram of the diaphragm has a high cross-correlation (an average of 0.91 +/- 0.06) with the transdiaphragmatic pressure, with a delay varying between 25 and 35 ms. The instantaneous frequency response of the phonomyogram of the diaphragm shows a behaviour similar to that of the frog muscle; it rapidly rises and then fades out. However, the maximum of the instantaneous frequency of the phonomyogram of the diaphragm is not proportional to the maximum of the transdiaphragmatic pressure. This analysis also demonstrates the usefulness of the cone-kernel distribution for studying frequency-modulated signals like the muscular sound signals.

Background: Neurochemical disorders associated with spinocerebellar ataxias are multiple. Objective: To use replacement and neuroprotective therapy in a case of severe respiratory failure in Friedreich ataxia. Patient and Treatment: A 44-year-old man with severe Friedreich ataxia displayed arduous periodic breathing associated with minor desaturation as well as obstructive or mixed apneas associated with severe desaturation during the night. He was given oxitriptan (5-hydroxy-L-tryptophan) (1500 mg/d), thiamine hydrochloride (100 mg/d), and amantadine hydrochloride (100 mg/d). The first sleep study was conducted during the night before treatment, whereas the second was performed during the night after 9 months of treatment. Results: After treatment, striking clinical improvement of spastic dysphonia was accompanied by significant diminution in the time spent in periodic breathing and in the number of obstructive and mixed apneas during the night. Controlled studies are needed.

BACKGROUND: A diaphragmatic phonomyogram (PMG) evoked by maximal phrenic nerve stimulation at end expiratory lung volume (FRC) has been previously described as a good index of changes in diaphragmatic contractility with fatigue. A study was undertaken to assess whether this conclusion could be extended to different lung volumes. METHODS: Diaphragmatic compound motor action potentials (CMAPs) were recorded on each side of the chest by the means of surface electrodes placed over the eight intercostal spaces in five healthy subjects. Diaphragmatic PMGs from both sides were recorded with condenser microphones fixed to the skin close to the CMAP recording electrodes. Oesophageal and gastric balloon tipped catheters were employed to measure transdiaphragmatic pressure twitches (TwPDI) which served as the standard measure of changes in diaphragmatic contractility. PMG and TwPDI responses were compared at different lung volumes over inspiratory capacity both before and after fatiguing inspiratory resistive loading. RESULTS: No consistent relationship was found in different subjects or on different days in the same subject between PMG and lung volume or between PMG and TwPDI. However, the PMG:CMAP ratio from both sides at any given lung volume decreased after fatigue in roughly the same proportion as the TwPDI. CONCLUSIONS: These results show that, although PMG can detect changes in diaphragmatic contractility caused by fatigue in normal subjects, lung volume changes need to be controlled and each subject should serve as his or her own control.

Objectives: To compare the distribution of lung volume at total lung capacity (TLC) among adult men and women known to have normal lung function or chronic obstructive disease or restrictive lung disease (RLD). Design: Five-year retrospective study. Setting: Review of available clinical pulmonary function testing (PFT) reports and chest radiographs. Patients: Sixty-four patients presenting with normal PFT and chest radiograph findings (normal subjects), 26 patients with severe COPD and increased TLC (COPD group), 29 patients with cystic fibrosis (CF) and increased TLC (CF group), and 19 patients with RLD with a clinical diagnosis of pulmonary fibrosis and a reduced TLC (RLD group). Measurements: Average posteroanterior rib cage diameter (PAave), average lateral rib cage diameter (LAave), and average vertical height of the diaphragm (HDIave) were measured using radiography. Normal prediction equations were generated based on stature, body mass index (BMI), age, and sex as independent variables and then used in between-group comparisons. Results: PAave correlated positively with BMI and age but not with height, whereas LAave correlated positively with BMI and height but not with age. HDIave correlated positively with height and age but negatively with BMI. PAave and LAave were smaller and HDIave was greater in women than men having the same stature. In the COPD group and in male CF group patients, BMI was low and only HDIave was greater than in sex-, age-, and height-matched normal subjects, but in female CF group patients, only the rib cage diameters were greater than normal. In the RLD group, PAave and HDIave were smaller than predicted and inversely related to each other, but LAave was normal. Conclusion: Variations in maximum lung volume caused by gender, growth, or by lung diseases are nonisotropic and entail substantial changes in chest wall shape. (CHEST 2001; 119:376 ‐386)

BACKGROUND: A greater structural expansion of the rib cage in females compared with males has been described in cystic fibrosis (CF) patients; however, conflicting data exist as to whether an elongation of the bony ribs and sternum contributes to this expansion.OBJECTIVES: To compare height-adjusted anthropometric measures and sternum length between a group of normal subjects and a group of CF patients of both sexes.METHODS: Anthropometric measurements including body weight, height, upper and lower limb lengths, biacromial distance and pelvic width were measured in the standing position in 30 CF patients (13 males) and 28 normal subjects (14 males). Body surface measurements of anterior-posterior and lateral diameters of the rib cage at functional residual capacity, and sternum length were also obtained.RESULTS: Compared with normal subjects, CF patients had lower body weight, shorter standing height and shorter height-adjusted upper and lower limb lengths. Rib cage diameters were greater in CF patients than in normal subjects of either sex, but height-adjusted sternum length was not different.CONCLUSION: Significant differences in bodily proportions were found between normal subjects and CF patients, suggesting a differential growth pattern for the trunk and limbs. However, increased rib cage dimensions with lung hyperinflation and airway obstruction was not associated with an elongation of the sternum.

The relative invasiveness of the balloon catheter technique in measuring twitch transdiaphragmatic pressure (Pdit) limits its clinical use. By phrenic stimulation we obtained swings in mouth pressure (Pmt) in six COPD patients (age 50 to 72, FEV1 18 to 48% of predicted) at relaxed FRC (rFRC) and during graded inspiratory efforts (IE; twitch occlusion, TO). At rFRC, Pmt was damped and time lagged relative to the esophageal pressure twitch (Pes(t)), as if pressure had equilibrated through an RC system. Pmt was not correlated with Pdit. Conversely, Pmt and Pes(t) were always well matched during IE [Pmt = 0.971 (SEM +/- 0.028) Pes(t), r > 0.89], possibly in relation to a decrease in upper airway compliance or more uniform pleural pressure swings. Pmt decreased with the level of voluntary diaphragmatic contraction (Pdivol) in proportion to Pdit, reflecting a progressive increase in the level of diaphragm activation. During IE, Pmt was closely related to the voluntary mouth pressure in five subjects but not in the remaining subject, indicating intersubject variability in the level of diaphragmatic recruitment relative to other inspiratory muscles. We submit that measuring Pm during inspiratory efforts upon which bilateral phrenic stimulation is superimposed offers a relatively simple method for the assessment of diaphragm activation, potentially applicable in the clinical field.

BACKGROUND/OBJECTIVES: The Epworth Sleepiness Scale (ESS) measures sleepiness and is used for, among others, patients with obstructive sleep apnea (OSA). The questionnaire is usually self-administered, but may be physician administered. The aim was to compare the two methods of administration and to validate a French version.METHODS: Consecutive patients presenting to the sleep clinic at a tertiary care centre completed a self-administered questionnaire containing the ESS. During the medical interview the same day, one of three pulmonologists who specialized in sleep medicine administered the ESS. Correlations with the apnea-hypopnea index and mean sleep latencies were used to assess construct validity, while results of previous self-administered ESS questionnnaires in untreated and recently treated OSA patients were used to test reproducibility and longitudinal construct validity, respectively.RESULTS: In OSA patients, the ESS weakly correlated with the apnea-hypopnea index (r=0.224; P=0.05; n=120) and negatively with mean sleep latency. For untreated patients (test-retest), the mean (± SD) average score was unchanged (10.3±6.0 to 10.8±6.5; P=0.35; n=56) after a median of seven months. With continuous positive airway pressure use, the mean score decreased from 12.4±6.8 to 7.6±5.0 after 40.2 months (Pttest]; n=188).CONCLUSIONS: In a sleep clinic population, the French version of the ESS performed similarly to the English version. However, the systematic underscoring during physician administration may be important to consider in the research setting if questionnaire administration methods are not consistent.

Mouth (PmT), esophageal (PesT), and transdiaphragmatic pressure twitches (PdiT) in response to single supramaximal bilateral phrenic nerve shocks were recorded during relaxation between total lung capacity (TLC) and functional residual capacity (FRC) in five normal volunteers. The PmT versus PesT or PmT versus PdiT relationships, which were linearly correlated (all r greater than 0.76), were not affected by diaphragm fatigue and were reproducible on repeated determinations over a period exceeding 1 yr. The PmT versus lung volume relationship was also linear (all r greater than 0.72) and reproducible, and its changes following diaphragm fatigue reliably reflected the changes in diaphragm contractility. We conclude that PmT is a reliable measure of diaphragm pressure-generating capacity in normal individuals and has the potential of providing similar information in patients.

In patients with chronic obstructive pulmonary disease (COPD) and hyperinflation of the lungs, dysfunction of the diaphragm may contribute to respiratory decompensation. We evaluated the contractile function of the diaphragm in well-nourished patients with stable COPD, using supramaximal, bilateral phrenic-nerve stimulation, which provides information about the strength and inspiratory action of the diaphragm.In eight patients with COPD and five control subjects of similar age, the transdiaphragmatic pressure generated by the twitch response to phrenic-nerve stimulation was recorded at various base-line lung volumes, from functional residual capacity to total lung capacity, and during relaxation and graded voluntary efforts at functional residual capacity (twitch occlusion).At functional residual capacity, the twitch transdiaphragmatic pressure ranged from 10.9 to 26.6 cm of water (1.07 to 2.60 kPa) in the patients and from 19.8 to 37.1 cm of water (1.94 to 3.64 kPa) in the controls, indicating considerable overlap between the two groups. The ratio of esophageal pressure to twitch transdiaphragmatic pressure, an index of the inspiratory action of the diaphragm, was -0.50 +/- 0.05 in the patients, as compared with -0.43 +/- 0.02 in the controls (indicating more efficient inspiratory action in the patients than in the controls). At comparable volumes, the twitch transdiaphragmatic pressure and esophageal-to-transdiaphragmatic pressure ratio were higher in the patients than in normal subjects, indicating that the strength and inspiratory action of the diaphragm in the patients were actually better than in the controls. Twitch occlusion (a measure of the maximal activation of the diaphragm) indicated near-maximal activation in the patients with COPD, and the maximal transdiaphragmatic pressure was 106.9 +/- 13.8 cm of water (10.48 +/- 1.35 kPa).The functioning of the diaphragms of the patients with stable COPD is as good as in normal subjects at the same lung volume. Compensatory phenomena appear to counterbalance the deleterious effects of hyperinflation on the contractility and inspiratory action of the diaphragm in patients with COPD. Our findings cast doubt on the existence of chronic fatigue of the diaphragm in such patients and therefore on the need for therapeutic interventions aimed at improving diaphragm function.

Injury to the alveolocapillary barrier characterizes ALI/ARDS; therefore determining levels of lung epithelium-specific small proteins in serum may help predict clinical outcomes. We examined whether serum Clara cell protein (CC-16) concentration is correlated with the outcome, mechanical ventilation duration, and incidence of nonpulmonary organ failure.Prospective multicenter observational study conducted by the Quebec Critical Care Network.Seventy-eight adult ARDS patients requiring mechanical ventilation were enrolled and 28-day mortality was the primary outcome. Ventilatory parameters were computed and blood was sampled daily. Clinical information collected included cause of death, duration of mechanical ventilation, number of ventilator-free days, and organ failures.Median serum levels of CC-16 were significantly higher in nonsurvivors than survivors on days 0-2 (19.93 microg/l, IQR 11.8-44.32, vs. 8.9, 5.66-26.38) and sustained up to day 14. CC-16 levels were correlated positively with the number of failing organs (rho 0.3623) and requirement for prolonged mechanical ventilation. Predictors of patient mortality included age, arterial carbon dioxide partial pressure, CC-16, and APACHE II score (odds ratios 1.35, 1.52, 1.37, 1.159, respectively).Higher initial CC-16 serum level is associated with increased risk of death, fewer ventilator-free days, and increased frequency of nonpulmonary multiple organ failure. CC-16 is a valuable biomarker of ARDS that may help predict outcome among ARDS patients with high-risk mortality.

Background Contracting muscle emits sounds. The purpose of this study was to compare the time course of muscular paralysis at the adductor pollicis muscle (AP) with use of acoustic myography and mechanomyography. Methods Thirteen elective surgery patients, American Society of Anesthesiologists physical status I, received rocuronium (0.6 mg/kg intravenously) as a bolus dose during general anesthesia. Force of AP was measured with use of a strain gauge, and sounds were recorded simultaneously with use of a small condenser microphone fixed on the palmar surface of the hand over the AP. Supramaximal stimulation was applied to the ulnar nerve at 0.1 Hz for 45-60 min. In seven patients, the response to train-of-four stimulation was also recorded during recovery. Results Force and sounds both were equally sensitive in measuring maximum block. The relation between sound and force was curvilinear, with good agreement near 0 and 100% and acoustic response exceeding mechanical response at intermediate levels of block. The acoustic signal had a slower onset and a faster recovery than the force response. The fade response of sound to train-of-four stimulation also recovered faster than that of force. Conclusion Acoustic myography is an alternative method to monitor muscular paralysis that is easy to set up and applicable to most superficial muscles. However, the time course of relaxation at AP using acoustic myography differs from the time course of force relaxation. Therefore, these two methods are not equivalent when applied to AP.

Diaphragmatic phonomyogram (PMG) evoked by maximal bilateral phrenic nerve stimulation has previously been described as a good index of contractility of fresh and fatigued diaphragm. In the present study we hypothesized that diaphragmatic contractility changes could be even more simply evaluated by recording the relationship between the PMG and the compound motor action potential (CMAP) amplitudes during graded submaximal unilateral phrenic nerve stimulation at various intensities. Relationships between CMAPs and PMGs from left and right hemidiaphragms were recorded by means of surface electrodes and miniature microphones placed over the lower rib cage (eighth intercostal space) in five healthy subjects before and after a diaphragmatic fatigue task. These relationships in each subject were linear. The slope of these relationships decreased by 61.1 +/- 20.7% and by 70.4 +/- 14.6% on the right and left side respectively, but the intercepts did not change significantly. By comparison, transdiaphragmatic twitch pressure during maximal bilateral stimulation (PdiT) declined by 49.4 +/- 15%. We conclude that PMG during submaximal unilateral phrenic nerve stimulation is a reliable index of diaphragm contractility changes caused by fatigue. Using this method we have shown that all diaphragmatic motor units can be affected by fatigue.

Normal subjects can increase their capacity to sustain hyperpnoea by bracing their arms on fixed objects, a procedure which is also known to reduce dyspnoea in patients with chronic obstructive pulmonary disease (COPD). In the present study, it was tested whether bracing per se could improve the function of the diaphragm. The effect of bracing on diaphragm function was studied in six normal subjects by recording changes in oesophageal (delta Poes) and transdiaphragmatic (delta Pdi) pressure during inspiratory capacity (IC) manoeuvres in the seated and upright postures, and in the seated posture, also during bilateral phrenic nerve stimulation (BPNS) at functional residual capacity (FRC). The pattern of ribcage motion and deformation associated with bracing and with diaphragm contraction was also evaluated using inductance plethysmography and magnetometers. Bracing increased FRC by >300 mL and reduced IC by approximately 200 mL, in both postures. Delta Pdi during BPNS decreased on average by 15% indicating an impaired diaphragmatic function. The ribcage was deformed with bracing and was more distortable during BPNS. In conclusion, in normal subjects, bracing impairs the function of the inspiratory muscles and reduces ribcage stability. These negative effects cannot explain the improved capacity to sustain hyperpnoea when the arms are braced.