Long-term effectiveness of a cognitive behavioural therapy (CBT) in the management of fatigue in patients with relapsing remitting multiple sclerosis (RRMS): a multicentre, randomised, open-label, controlled trial versus standard care.

BACKGROUND: Fatigue is a disabling symptom of multiple sclerosis (MS). The lack of effective therapeutics has promoted the development of cognitive behavioural therapy (CBT)-based fatigue management programmes. However, their efficacy does not sustain over time. We proposed to test the long-term effectiveness of a 6-week fatigue programme supplemented with four booster sessions ('FACETS+') in patients with relapsing remitting MS (RRMS) and fatigue. METHODS: This multicentre, randomised, controlled, open-label, parallel-group trial versus standard care enrolled patients with RRMS and fatigue. Participants were randomised to either FACETS+ plus standard care or standard care alone. The primary outcome measure was fatigue impact (Modified Fatigue Impact Scale (MFIS) at 12 months) based on intention-to-treat analyses. RESULTS: From May 2017 to September 2020, 162 patients were screened; 105 were randomly assigned to FACETS+ (n=57) or standard care (n=48) and 88 completed the primary outcome assessment for the MFIS. At month 12, participants showed improved MFIS compared with baseline in the intervention group (mean difference (MD)=14.0 points; (95% CI 6.45 to 21.5)) and the control group (MD=6.1 points; (95% CI -0.30 to 12.5)) with a significant between-group difference in favour of the intervention group (adjusted MD=7.89 points; (95% CI 1.26 to 14.52), standardised effect size=0.52, p=0.021). No trial-related serious adverse events were reported. CONCLUSIONS: A 6-week CBT-based programme with four booster sessions is superior to standard care alone to treat MS-related fatigue in the long term (12 months follow-up). The results support the use of the FACETS+ programme for the treatment of MS-related fatigue. TRIAL REGISTRATION NUMBER: NCT03758820.

Efficacy of ceftazidime/avibactam in various combinations for the treatment of experimental osteomyelitis in rabbits caused by OXA-48-/ESBL-producing Escherichia coli.

BACKGROUND: While the treatment of ESBL-producing Enterobacterales osteomyelitis relies on carbapenems, the optimal regimen for OXA48 types remains unclear. We evaluated the efficacy of ceftazidime/avibactam in different combinations in an experimental model of OXA-48-/ESBL-producing Escherichia coli osteomyelitis. METHODS: E. coli pACYC184 is a clinical strain harbouring blaOXA-48 and blaCTX-M-15 inserts, with 'increased exposure susceptibility' to imipenem (MIC, 2 mg/L), gentamicin (MIC, 0.5 mg/L), colistin (MIC, 0.25 mg/L), ceftazidime/avibactam (MIC, 0.094 mg/L) and fosfomycin (MIC, 1 mg/L), and resistance to ceftazidime (MIC, 16 mg/L). Osteomyelitis was induced in rabbits by tibial injection of 2 × 108 cfu of OXA-48/ESBL E. coli. Treatment started 14 days later for 7 days in six groups: (1) control, (2) colistin 150.000 IU/kg subcutaneously (SC) q8h, (3) ceftazidime/avibactam 100/25 mg/kg SC q8h, (4) ceftazidime/avibactam + colistin, (5) ceftazidime/avibactam + fosfomycin 150 mg/kg SC q12h, (6) ceftazidime/avibactam + gentamicin 15 mg/kg intramuscularly (IM) q24h. Treatment was evaluated at Day 24 according to bone cultures. RESULTS: In vitro, time-kill curves of ceftazidime/avibactam in combination showed a synergistic effect. In vivo, compared with controls, rabbits treated with colistin alone had similar bone bacterial density (P = 0.50), whereas ceftazidime/avibactam alone or in combinations significantly decreased bone bacterial densities (P = 0.004 and P < 0.0002, respectively). Bone sterilization was achieved using ceftazidime/avibactam in combination with colistin (91%) or fosfomycin (100%) or gentamicin (100%) (P < 0.0001), whereas single therapies were not different from controls. No ceftazidime/avibactam-resistant strains emerged in rabbits treated, regardless of the combination. CONCLUSIONS: In our model of E. coli OXA-48/ESBL osteomyelitis, ceftazidime/avibactam in combination was more effective than any single therapy, whatever the companion drug used (gentamicin or colistin or fosfomycin).

Adherence to continuous positive airway pressure therapy in patients with spinal cord injury and obstructive sleep apnea: trajectories and predictors.

PURPOSE: To identify specific determinants of non-adherence or cessation of continuous positive airway pressure (CPAP) therapy in a population of patients with spinal cord injuries (SCI). METHODS: Retrospective analysis of data from patients with SCI who underwent a full night supervised polysomnography between 2015 and 2021 and presented with moderate to severe obstructive sleep apnea (OSA) and for whom CPAP was indicated. Adherence was studied at 1, 6, and 12 months. Univariate and multivariate analyses were performed to identify factors associated with non-adherence (< 4 h per night or CPAP cessation). Factors studied were demographic and disease-related data and both subjective and objective sleep parameters. RESULTS: A total of 60 patients were included (40% cervical SCI). In univariate analysis, the only predictive parameters of non-adherence observed at 1, 6, and 12 months were the average use of CPAP on the 1st night (p = 0.02) and over the 1st week (p ≤ 0.001). A complete lesion (AIS-A) was predictive of non-adherence at 1 and 6 months (p = 0.02 at 6 months), while mask leakage was associated with non-adherence at 12 months (p = 0.02). Upper limb autonomy and the presence of family caregivers did not appear to be protective. In multivariate analysis, only the average use in the first week remained predictive of adherence (> 4 h) in the short, medium and long term. CONCLUSION: In patients with SCI and OSA, the 1st week of CPAP treatment seems to be determinant of short-, medium-, and long-term CPAP adherence. Support for SCI patients from the start of treatment is essential and may help avoid treatment failures.

Perioperative complications after posterior spinal fusion versus minimally invasive fusionless surgery in neuromuscular scoliosis: a comparative study.

INTRODUCTION: Early-onset scoliosis is a common deformity in neuromuscular disease. When conservative treatment becomes ineffective, several surgical options can be proposed. The most common technique is posterior spinal fusion (PSF) consisting of performing a multiple segmental instrumentation with pedicular screws on the full spine associated with decortication and bone graft. Minimally invasive fusionless surgery (MIFS) is an alternative to correct and fix definitively the spine without graft. The objective of this study was to compare early surgical inpatient period between PSF and MIFS in neuromuscular scoliosis. MATERIAL AND METHODS: 140 NMS operated by PSF or MIFS between 2012 and 2017 was retrospectively reviewed. The following data were compared between groups: general characteristics (age, sex, etiology), preoperative preparation (halo traction, noninvasive ventilation or tracheostomy), Cobb angle and pelvic obliquity correction, use of drugs (vasopressor and/or inotropes, expansion fluids, transfusion and volumes), postoperative complications, and need of noninvasive ventilation. RESULTS: 75 patients were managed by PSF with a mean age of 14.3 ± 2.3y and 65 by MIFS with a mean age of 11.8 ± 3y. Average pelvic obliquity and major curve correction were similar postoperatively. Intraoperative blood transfusion was significantly more common in PSF group (OR, 14; 95% CI [6.3-33.0]). Vasopressors were used non-significantly more often in the PSF group and expansion fluids similar in the two groups. PSF group had more overall complications (OR, 4.6; 95% CI [2.3-9.8]), more infections (OR, 3.6; 95% CI [1.5-9.3]) and more hemodynamic complications (OR, 4.1; 95% CI [1.4-15.1]). Average intubation duration was 5 days in the PSF and 4 days in MIFS (p = 0.05). CONCLUSION: In this series of neuromuscular patients, the complication rate was reduced in MIFS comparatively to PSF, with lower blood transfusion and less infections.

Pediatric Acute Alcohol Intoxication Admitted to the ICU: A Review of 102 Cases in France.

OBJECTIVES: To describe the profile and clinical outcomes of children (<18 yr) admitted to intensive care for acute alcohol intoxication, with special attention to complications and to the subgroup that required intubation. DESIGN: Retrospective observational study. SETTING: Seven pediatric and three adult ICUs in France. PATIENTS: Children 1-17 yr admitted to intensive care for acute alcohol intoxication between January 1, 2010, and December 30, 2017. INTERVENTIONS: The study was observational and patients received standard care. MEASUREMENTS AND MAIN RESULTS: We included 102 patients, with 71 males (69.6%) and 31 females (30.4%). Mean age was not different between males and females (14.0 ± 3.0 yr [range, 2-17 yr] and 14.2 ± 1.3 yr [range, 11-17 yr]; p = 0.67); six children were younger than 10 years. Mean blood alcohol concentration was not significantly different in males and females (2.42 ± 0.86 and 2.20 ± 0.54 g/L, respectively; p = 0.51). Of the 102 patients, 58 (57%) required intubation. Factors significantly associated with requiring intubation were lower Glasgow Coma Scale score (p = 0.002), lower body temperature (p = 0.045), and higher blood alcohol concentration (p = 0.012); vascular filling, and electrolyte disturbances were not associated with needing intubation. Mean intubation time was 9.7 ± 5.2 hours. Among the 59 patients with Glasgow Coma Scale score less than 8, 12 did not require intubation. The most common metabolic disturbance was a high lactate level (48%), followed by hypokalemia (27.4%); 59 (58.2%) patients had hyperglycemia and three had hypoglycemia. CONCLUSIONS: Male adolescents make up the majority of pediatric patients admitted to intensive care for acute alcohol intoxication. A need for intubation was associated with a worse Glasgow Coma Scale, lower body temperature, and higher blood alcohol concentration. Intubation was usually required for less than 12 hours. Other acute medical complications reported in adults with acute alcohol intoxication, such as electrolyte disturbances and aspiration pneumonia, were rare in our pediatric patients.

Impact of a medication reconciliation care bundle at hospital discharge on continuity of care: A randomised controlled trial.

OBJECTIVE: To compare the impact of a care bundle including medication reconciliation at discharge by a pharmacist versus standard of care, on continuity of therapeutic changes between hospital and primary care and outcome of patients, within 1 month after discharge. METHODS: Randomised controlled trial in 120 adult patients with at least one chronic disease and three current medications before admission, hospitalised in an infectious disease department of a tertiary hospital and discharged home. Patients were randomly assigned (1:1) to receive a discharge care bundle including medication reconciliation, counselling session and documentation transfer to primary care physician (PCP) (intervention group) or standard of care (control group). Primary outcome was the proportion of in-hospital prescription changes, not maintained by the PCP, 1 month after discharge. Secondary outcome measures included the proportion of patients experiencing early PCP's consultation, hospital readmissions or adverse reactions within 1-month postdischarge and cost of discharge prescriptions. RESULTS: Baseline characteristics were comparable between the two groups. One month after discharge, the proportion of in-hospital prescription changes, not maintained by the PCP, was 11% in the intervention group versus 24% in the control group (P = .007). The median delay before PCP's consultation was longer in the intervention group (30.5 vs 19.5 days, P = .013), there were fewer patients readmitted to hospital (3.4% vs 20.7%, P = .009, odds ratio (OR) = 0.13 [0.02-0.53]) and fewer patients who suffered from adverse drug reaction (7.0% vs 22.8%, P = .04, OR = 0.26 [0.07-0.78]). CONCLUSION: This care bundle resulted in the reduction of treatment changes between hospital discharge and primary care.

Impact of Combined Transcranial Direct Current Stimulation and Speech-language Therapy on Spontaneous Speech in Aphasia: A Randomized Controlled Double-blind Study.

OBJECTIVE: Aphasia recovery depends on neural reorganization, which can be enhanced by speech-language therapy and noninvasive brain stimulation. Several studies suggested that transcranial direct current stimulation (tDCS) associated with speech-language therapy may improve verbal performance evaluated by analytic tests, but none focused on spontaneous speech. We explored the effect of bihemispheric tDCS on spontaneous speech in patients with poststroke aphasia. METHODS: In this multicentric controlled randomized cross-over double-blind study, we included 10 patients with poststroke aphasia (4 had aphasia >6 months and 6 with aphasia <6 months). We combined the sessions of speech-language therapy and bihemispheric tDCS (2 mA, 20 min). After three baseline speech evaluations (1/week), two different conditions were randomly consecutively proposed: active and sham tDCS over 3 weeks with 1 week of washout in between. The main outcome measure was the number of different nouns used in 2 min to answer the question "what is your job." RESULTS: There was no significant difference between conditions concerning the main outcome measure (p = .47) nor in the number of verbs, adjectives, adverbs, pronouns, repetitions, blank ideas, ideas, utterances with grammatical errors or paraphasias used. Other cognitive functions (verbal working memory, neglect, or verbal fluency) were not significantly improved in the tDCS group. No adverse events occurred. CONCLUSION: Our results differed from previous studies using tDCS to improve naming in patients with poststroke aphasia possibly due to bihemispheric stimulation, rarely used previously. The duration of the rehabilitation period was short given the linguistic complexity of the measure. This negative result should be confirmed by larger studies with ecological measures.

Blue-Enriched White Light Therapy Reduces Fatigue in Survivors of Severe Traumatic Brain Injury: A Randomized Controlled Trial.

OBJECTIVE: Fatigue is one of the disabling sequelae of traumatic brain injury (TBI), with repercussions on quality of life, rehabilitation, and professional reintegration. Research is needed on effective interventions. We evaluated efficacy of blue-enriched white light (BWL) therapy on fatigue of patients with severe TBI. SETTING: Physical Medicine and Rehabilitation and Physiology departments of University hospitals. PARTICIPANTS: Adult patients with fatigue symptoms following severe TBI, Fatigue Severity Scale (FSS) score 4 or more, Epworth Sleepiness Scale (ESS) score 10 or more, and/or Pittsburgh Sleep Quality Index (PSQI]) more than 5 were randomly assigned to one of 2 parallel groups: a BWL therapy group, with 30-minute exposure to waking white light enriched with blue for 4 weeks, and a group without light therapy (N-BWL), no light. DESIGN: Randomized controlled trial. ClinicalTrials.gov number: NCT02420275. MAIN MEASURES: The primary outcome measure was the response of the FSS to 4 weeks of treatment. In addition, we assessed latency change of the P300 component of event-related potentials before and after therapy. RESULTS: Significant improvement in the FSS score (P = .026) was found in the BWL group compared with the N-BWL group. CONCLUSION: BWL phototherapy reduces fatigue in patients with severe TBI.

Effect of Smoked Cannabis on Vigilance and Accident Risk Using Simulated Driving in Occasional and Chronic Users and the Pharmacokinetic-Pharmacodynamic Relationship.

BACKGROUND: The pharmacokinetic-pharmacodynamic relationship between whole blood δ-9-tetrahydrocannabinol (THC) and driving risk is poorly understood. METHODS: Fifteen chronic cannabis consumers (1-2 joints/day; CC) and 15 occasional cannabis consumers (1-2 joints/week; OC) of 18 to 34 years of age were included. A pharmacokinetic study was conducted with 12 blood samplings over a 24-h period before and after controlled random inhalation of placebo or 10 mg or 30 mg of THC. THC and metabolites were quantified using LC-MS/MS. Effects on reaction time by psychomotor vigilance tests and driving performance through a York driving simulator were evaluated 7 times. A pharmacokinetic-pharmacodynamic analysis was performed using R software. RESULTS: Whole blood peak THC was 2 times higher in CC than in OC for a same dose and occurred 5 min after the end of consumption. THC remained detectable only in CC after 24 h. Despite standardized consumption, CC consumed more available THC from each cigarette regardless of dose. Maximal effect for reaction time was dose- and group-dependent and only group-dependent for driving performance, both being decreased and more marked in OC than in CC. These effects were maximal around 5 h after administration, and the duration was longer in OC than in CC. A significant pharmacokinetic-pharmacodynamic relationship was observed only between T max for blood THC and the duration effect on mean reciprocal reaction time. CONCLUSIONS: Inhalation from cannabis joints leads to a rapid increase in blood THC with a delayed decrease in vigilance and driving performance, more pronounced and lasting longer in OC than in CC. ClinicalTrials.gov Identifier: NCT02061020.

Influence of training protocols on text input speed on a computer in individuals with cervical spinal cord injury: a randomised controlled trial.

STUDY DESIGN: Randomised controlled trial. OBJECTIVES: To evaluate the impact of two different word prediction software (WPS) training protocols on text input speed (TIS) in people with tetraplegia and to determine which was the most effective. SETTING: Rehabilitation department, Garches, France. METHODS: Participants with neurological levels between C6 and C8 were allocated to one of three different groups. The REHAB group underwent training with an occupational therapist. The SELF group carried out a standardised home self-training with a written training guide. The CONTROL group had no training. Participants were assessed at day 15 (D15) and day 30 (D30). The primary outcome was a copying task with and without WPS (WITH and WITHOUT). RESULTS: Forty-two participants (mean age ± SD of 39.8 ± 12) were included and 38 completed the study. At D30, the mean (95% confidence interval) difference in TIS between the CONTROL and SELF groups was 3.8 [-1.7 to 9.4] characters per minute (cpm) (p = 0.23), between the REHAB and SELF groups was 12.9 [7.4 to 18.4] cpm (p < 0.001), and between the REHAB and CONTROL groups was 9.1 [3.5 to 14.6] cpm (p < 0.001). CONCLUSIONS: The results of this study showed that occupational therapist-supervised training improved TIS but word prediction software did not increase TIS. These results suggest that supervised training should be provided to all individuals who are prescribed with devices and systems to facilitate computer access in order to increase their TIS.

Long-term outcomes and risks factors for failure of intradetrusor onabotulinumtoxin A injections for the treatment of refractory neurogenic detrusor overactivity.

AIMS: Aims of this study were to assess the long-term outcomes of Intradetrusor injection of OnabotulinumtoxinA (Botox® injection) associated with clean intermittent-catheterization (CIC) for the treatment of neurogenic detrusor overactivity (NDO) and to identify risk factors for failure. METHODS: Neurological patients with NDO using CIC who had received Botox® injections between January 2001 and September 2013 were included. Clinical, urodynamic and radiological data were recorded. Primary endpoint was failure and withdrawal rates after 3, 5, and 7 years of management. Survival curves of withdrawals and failures of treatment were calculated with a 95-confidence interval using the Kaplan-Meier method. Risk factors for failure were determined with univariate analysis and multivariate analysis using Cox model. RESULTS: Overall, 292 patients, mean age of 40 ± 13, 6 years, were included. Overall, 219 patients (80.6%; IC95% [76.3-85.4%]) were still treated with Botox® injections after 3 years, 128 (71.1%; IC95% [65.7%, 76.9%]) after 5 years, and 58 (60.8%, IC95% [54.0%, 68.4%]) after 7 years. Failure rate was 12.6% (IC95% [8.6-16.5%]) after 3 years, 22.2% (IC95% [16.6-27.3%]) after 5 years, and 28.9% (IC95% [21.9%; 35.3%]) after 7 years of follow-up. Withdrawal rate after 7 years of follow-up was 11.3% (n = 33/292). Severe NDO at baseline appears to be a significant risk factor for failure. CONCLUSION: This study confirms long-term efficacy and tolerance of Botox® injection in patients with NDO using CIC. Long-term failure and withdrawal rates remain low but significant, and need to be managed.

Effects of Bracing in Adult With Scoliosis: A Retrospective Study.

OBJECTIVE: To assess the effectiveness of bracing in adult with scoliosis. DESIGN: Retrospective cohort study. SETTING: Outpatients followed in 2 tertiary care hospitals. PARTICIPANTS: Adults (N=38) with nonoperated progressive idiopathic or degenerative scoliosis treated by custom-molded lumbar-sacral orthoses, with a minimum follow-up time of 10 years before bracing and 5 years after bracing. Progression was defined as a variation in Cobb angle ≥10° between the first and the last radiograph before bracing. The brace was prescribed to be worn for a minimum of 6h/d. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: Rate of progression of the Cobb angle before and after bracing measured on upright 3-ft full-spine radiographs. RESULTS: At the moment of bracing, the mean age was 61.3±8.2 years, and the mean Cobb angle was 49.6°±17.7°. The mean follow-up time was 22.0±11.1 years before bracing and 8.7±3.3 years after bracing. For both types of scoliosis, the rate of progression decreased from 1.28°±.79°/y before to .21°±.43°/y after bracing (P<.0001). For degenerative and idiopathic scoliosis, it dropped from 1.47°±.83°/y before to .24°±.43°/y after bracing (P<.0001) and .70°±.06°/y before to .24°±.43°/y after bracing (P=.03), respectively. CONCLUSIONS: For the first time, to our knowledge, this study suggests that underarm bracing may be effective in slowing down the rate of progression in adult scoliosis. Further prospective studies are needed to confirm these results.

Influence of the Number of Predicted Words on Text Input Speed in Participants With Cervical Spinal Cord Injury.

OBJECTIVES: To determine whether the number of words displayed in the word prediction software (WPS) list affects text input speed (TIS) in people with cervical spinal cord injury (SCI), and whether any influence is dependent on the level of the lesion. DESIGN: A cross-sectional trial. SETTING: A rehabilitation center. PARTICIPANTS: Persons with cervical SCI (N=45). Lesion level was high (C4 and C5, American Spinal Injury Association [ASIA] grade A or B) for 15 participants (high-lesion group) and low (between C6 and C8, ASIA grade A or B) for 30 participants (low-lesion group). INTERVENTION: TIS was evaluated during four 10-minute copying tasks: (1) without WPS (Without); (2) with a display of 3 predicted words (3Words); (3) with a display of 6 predicted words (6Words); and (4) with a display of 8 predicted words (8Words). MAIN OUTCOME MEASURES: During the 4 copying tasks, TIS was measured objectively (characters per minute, number of errors) and subjectively through subject report (fatigue, perception of speed, cognitive load, satisfaction). RESULTS: For participants with low-cervical SCI, TIS without WPS was faster than with WPS, regardless of the number of words displayed (P<.001). For participants with high-cervical SCI, the use of WPS did not influence TIS (P=.99). There was no influence of the number of words displayed in a word prediction list on TIS; however, perception of TIS differed according to lesion level. CONCLUSIONS: For persons with low-cervical SCI, a small number of words should be displayed, or WPS should not be used at all. For persons with high-cervical SCI, a larger number of words displayed increases the comfort of use of WPS.

Nocturnal hypoventilation in neuromuscular disease: prevalence according to different definitions issued from the literature.

PURPOSE: Restrictive respiratory failure is a major cause of morbidity and mortality in neuromuscular diseases (NMD). Home mechanical ventilation (HMV) is used to treat hypoventilation, identified by daytime hypercapnia or nocturnal desaturation. Recently, transcutaneous measure of CO2 (TcCO2) has been increasingly used to detect hypoventilation, using different cut-offs. We aimed to compare the prevalence of hypoventilation in an unselected adult NMD population according to different definitions issued from the literature. METHODS: All consecutive nocturnal capno-oximetries performed between 2010 and 2014 in unventilated adult NMD patients were analysed retrospectively. Concomitant blood gas analysis and lung function data were collected. Patients on oxygen therapy were excluded. Hypoventilation was defined according to eight criteria, based on daytime PaCO2, daytime base excess, nocturnal SpO2 or TcCO2. RESULTS: Data from 232 patients were analysed (mean age 43.1 ± 15.4 years; 50.0 % women; vital capacity 59.2 ± 24.2 % of predicted). The hypoventilation prevalence was 10.3 to 61.2 %, depending on the used definition. The different definitions showed 49.1 to 94.8 % concordance (Cohen's kappa for agreement 0.115 to 0.763). Overall agreement between the eight definitions was poor (Light's kappa 0.267), and agreement between definitions based on nocturnal SpO2 and those based on TcCO2 was even lower (Light's kappa 0.204). CONCLUSIONS: We found large differences in hypoventilation prevalence according to the used definition. This has practical consequences, as HMV indication relies upon hypoventilation detection. We believe that capno-oximetry should be included in the diagnostic tools used to detect hypoventilation but this requires an update of consensus guidelines to agree upon the best definition.

Accuracy of tidal volume delivered by home mechanical ventilation during mouthpiece ventilation: A bench evaluation.

The aim of our study was to evaluate efficacy and reliability of currently available ventilators for mouthpiece ventilation (MPV). Five life-support home ventilators were assessed in a bench test using different settings simulating the specificities of MPV, such as intermittent circuit disconnection and presence of continuous leaks. The intermittent disconnection of the circuit caused relevant swings in the delivered tidal volume ( VT), showing a VT overshoot during the disconnection periods and a VT decrease when the interface was reconnected to the test lung. The five ventilators showed substantial differences in the number of respiratory cycles necessary to reach a stable VT in the volume-controlled setting, ranging from 1.3 ± 0.6 to 7.3 ± 1.2 cycles. These differences were less accentuated in the volume-assisted setting (MPV-dedicated mode, when available). Our data show large differences in the capacity of the different ventilators to deal with the rapidly changing respiratory load features that characterize MPV, which can be further accentuated according to the used ventilator setting. The dedicated MPV modes allow improvement in the performance of ventilators only in some defined situations. This has practical consequences for the choice of the ventilator to be used for MPV in a specific patient.

Evaluation of 3 pushrim-activated power-assisted wheelchairs in patients with spinal cord injury.

OBJECTIVE: To assess differences between manual wheelchairs and 3 pushrim-activated power-assisted wheelchairs (PAPAWs): Servomatic A and B and E-motion. DESIGN: Repeated measures. SETTING: Rehabilitation hospital. PARTICIPANTS: Volunteers with spinal cord injuries (N=52). INTERVENTIONS: Ten subjects propelled the wheelchairs on a dynamometer, 46 evaluated each wheelchair on indoor and outdoor courses, and 10 evaluated their ability to transfer themselves and their wheelchairs into and out of their car. MAIN OUTCOME MEASURES: Oxygen consumption per unit time (V˙o2) and heart rate were measured during propulsion on the dynamometer. Wheelchair efficiency on the indoor and outdoor courses was evaluated on the basis of heart rate, completion time, handrim push frequency, and patient satisfaction. RESULTS: On the dynamometer, decreases in V˙o2 and heart rate were similar with the 3 PAPAWs compared with manual wheelchairs. On the outdoor course, heart rate was significantly decreased by PAPAWs compared with manual wheelchairs and patient satisfaction was better with Servomatic devices than with the E-motion device. Indoors, the course completion time was longer with the E-motion wheelchair than with other wheelchairs in the overall population, and handrim push frequency was higher with the E-motion wheelchair than with other wheelchairs in the subgroup with T12 to L1 injuries. Car transfer ability was lower with PAPAWs than with manual wheelchairs. CONCLUSIONS: Differences exist across PAPAWs. Compared with E-motion, the 2 Servomatic PAPAWs were easier to use outdoors, and difficulty transferring into/out of the car was similarly increased with all 3 PAPAWs.

Comparison of three cough-augmentation techniques in neuromuscular patients: mechanical insufflation combined with manually assisted cough, insufflation-exsufflation alone and insufflation-exsufflation combined with manually assisted cough.

BACKGROUND: Mechanical insufflation-exsufflation (MI-E), more commonly known as 'cough assist therapy', is a method which produces inspiratory and expiratory assistance to improve cough performances. However, other alternatives or combinations are possible. OBJECTIVE: The objective was to compare the effects of mechanical insufflation combined with manually assisted coughing (MAC), insufflation-exsufflation alone and insufflation-exsufflation combined with MAC in neuromuscular patients requiring cough assistance. METHODS: Eighteen neuromuscular patients with severe respiratory muscle dysfunction and peak cough flow (PCF) lower than 3 liters/s or maximal expiratory pressure (MEP) lower than +45 cm H2O were studied. Patients were studied under three cough-assisted conditions, which were used in random order: insufflation by intermittent positive-pressure breathing (IPPB) combined with MAC, MI-E and MI-E + MAC. RESULTS: Overall, PCF was higher with IPPB + MAC than with MI-E + MAC or MI-E alone. Among the 12 patients who had higher PCF values with IPPB + MAC than with the two other techniques, 9 exhibited mask pressure swings during MI-E exsufflation, with a transient positive-pressure value due to the expiratory flow produced by the combined patient cough effort and MAC. Each of these 9 patients had higher PCF values (>5 liters/s) than did the other 9 patients when using IPPB + MAC. CONCLUSION: Our results indicate that adding the MI-E device to MAC is unhelpful in patients whose PCF with an insufflation technique and MAC exceeds 5 liters/s. This is because the expiratory flow produced by the patient's effort and MAC transitorily exceeds the vacuum capacity of the MI-E device, which therefore becomes a transient load against the PCF.

Normalization of eosinophil count is predictive of oxygen weaning over the course of COVID-19 infection among hospitalized adults during the first wave of 2020 pandemic.

Background: Understanding COVID-19 outcomes remains a challenge. While numerous biomarkers have been proposed for severity at admission, limited exploration exists for markers during the infection course, especially for the requirement of oxygen therapy. This study investigates the potential of eosinophil count normalization as a predictor for oxygen weaning during the initial wave of the pandemic. Methods: A retrospective study was conducted between March and April 2020 (first wave) among adults admitted directly to a medicine ward. Biological abnormalities, including lymphocyte count, eosinophil count, and C-reactive protein (CRP), were gathered daily during the first week of admission according to oxygen level. In case of worsening, oxygen level was censored at 15 L/min. The primary aim was to assess whether eosinophil count normalization predicts a subsequent decrease in oxygen requirements. Results: Overall, 132 patients were admitted, with a mean age of 59.0 ± 16.3 years. Of the patients, 72% required oxygen, and 20.5% were admitted to the intensive care unit after a median delay of 48 hours. The median CRP at admission was 79 (26-130) mg/L, whereas the eosinophil count was 10 (0-60)/mm3. Eosinophil count normalization (≥100/mm3) by day 2 correlated significantly with decreased oxygen needs (<2 L) with hazard ratio (HR) = 3.7 [1.1-12.9] (p = 0.04). Likewise, CRP < 80 mg/L was associated with reduced oxygen requirements (p < 0.001). Predictors, including underlying chronic respiratory disease, exhibited a trend toward a negative association (p = 0.06). Conclusion: The study highlights the relationship between eosinophil count and CRP, with implications for predicting oxygen weaning during COVID-19. Further research is warranted to explore the relevance of these biomarkers in other respiratory infections.

Efficacy of ceftazidime-avibactam in various combinations for the treatment of experimental osteomyelitis due to Klebsiella pneumoniae carbapenemase (KPC)-producing Klebsiella pneumoniae.

BACKGROUND: Optimal treatment of carbapenemase-producing Enterobacterales (CPE) bone infections is poorly defined. This study evaluated the efficacy of the novel beta-lactam-beta-lactamase inhibitor-ceftazidime-avibactam (CAZ-AVI)-with different antibiotic combinations in an experimental model of CPE osteomyelitis. METHODS: KPC-99YC is a clinical strain of Klebsiella pneumoniae carbapenemase (KPC)-producing Klebsiella pneumoniae with intermediate susceptibility to meropenem (MIC 4 mg/L), gentamicin (MIC 0.25 mg/L), colistin (MIC 0.25 mg/L), fosfomycin (MIC 4 mg/L) and ceftazidime-avibactam (MIC 1 mg/L). Time-kill curves were performed at 4x MIC. Osteomyelitis was induced in rabbits by tibial injection of 2×108 CFU of KPC-99YC. Six groups started treatment 14 days later for 7 days: control, colistin, CAZ-AVI, CAZ-AVI plus gentamicin, CAZ-AVI plus colistin and CAZ-AVI plus fosfomycin. Antibiotic dosages were selected to simulate plasma concentrations obtained in humans. Treatment was evaluated according to bone cultures quantified in log10 CFU. RESULTS: In vitro, CAZ-AVI plus colistin or gentamicin were rapidly bactericidal in contrast with CAZ-AVI plus fosfomycin. In vivo, compared with controls, colistin alone (P = 0.045) and CAZ-AVI alone or in combination significantly lowered bone bacterial counts (P < 0.001). Bone sterilisation was achieved in 67% and 100% of animals with combinations of CAZ-AVI plus colistin or gentamicin (P = 0.001 and P < 0.001, respectively) whereas other treatments were no different from controls. CAZ-AVI plus gentamicin provided greater bone bacterial reduction than CAZ-AVI plus colistin (P = 0.033). No CAZ-AVI-resistant strains emerged in treated rabbits, regardless of combination. CONCLUSIONS: CAZ-AVI plus gentamicin was the best effective combination therapy. Combinations with CAZ-AVI appear to be a promising treatment of KPC-producing Klebsiella pneumoniae osteomyelitis.

Comparison of Four Mechanical Insufflation-Exsufflation Devices: Effect of Simulated Airway Collapse on Cough Peak Flow.

BACKGROUND: Mechanical insufflation-exsufflation (MI-E) devices are used to improve airway clearance in individuals with acute respiratory failure. Some MI-E devices measure cough peak flow (CPF) during MI-E to optimize pressure adjustments. The aim was to compare CPF and effective cough volume (ECV: volume expired/coughed > 3 L/s) measurements between 4 MI-E devices under simulated conditions of stable versus collapsed airway. METHODS: Four MI-E devices were tested on the bench. Each device was connected via a standard circuit to a collapsible tube placed in an airtight chamber that was attached to a lung model with adjustable compliance and resistance. Pressure was measured upstream and downstream the collapsing tube; air flow was measured between the chamber and the lung model. Each device was tested in 2 conditions: collapse condition (0 cm H2O) and no-collapse condition (-70 cm H2O). For each condition, 6 combinations of inspiratory/expiratory pressures were applied. CPF was measured at the "mouth level" by the device built-in flow meter and at the "tracheal level" by a dedicated pneumotachograph. Comparisons were performed with non-parametric tests. RESULTS: CPF values measured at the tracheal level and ECV values differed between devices for each inspiratory/expiratory pressure in the collapse and no-collapse conditions (P < .001). CPF values were significantly lower at the tracheal level in the collapse as compared with the no-collapse condition (P < .001 for each device), whereas they were higher at the mouth level (P < .05) for 3 of the 4 devices. CONCLUSIONS: CPF values differed significantly across MI-E devices, highlighting limitation(s) of using only CPF values to determine cough effectiveness. In simulated of airway collapse, CPF increased at the mouth, whereas it decreased at the tracheal level.