Serial electrophysiology has been suggested as essential for accurate diagnosis in Guillain-Barré syndrome (GBS). However, whether more adapted electrophysiological criteria may allow a single study ...to be sufficient is unknown.
We retrospectively reviewed records of 365 consecutive patients with GBS from Birmingham, U.K., and Garches, France, admitted between 1998 and 2013. Electrophysiology was analysed using existing criteria as well as a set of modified criteria, developed using sensitive and specific cut-off values for demyelination and incorporating new knowledge on electrophysiology of axonal GBS. We compared diagnostic rates and classification changes using modified criteria with published literature relating to serial studies.
With existing criteria, we found similar proportions of acute inflammatory demyelinating polyradiculoneuropathy (AIDP) (71.5% vs. 72%; p=1), axonal GBS (17.5% vs. 14.7%; p=0.62) and equivocal forms (9.9% vs. 13.3%; p=0.41) to the previous studies considered. With modified criteria, we identified comparable rates of AIDP (56.2% vs. 58.7%; p=0.70), axonal GBS (35.1% vs. 36%; p=0.89) and equivocal forms (7.7% vs. 5.3%; p=0.63) with a single nerve conduction study as compared with when serial electrophysiology was used in previous analyses. We observed an identical diagnostic shift from AIDP to axonal GBS with modified criteria as that described with serial studies (21.5% vs. 18.5%; p=0.72). Classification changes with modified criteria correlated significantly with performing of electrophysiology ≤7 days after symptom onset (p=0.045), indicating their greater usefulness in earlier disease stages.
A single electrophysiological study may suffice to establish the ultimate electrodiagnosis of GBS subtype if the proposed modified electrodiagnostic criteria are used.
In patients with neuromuscular disorders, assessment of respiratory function relies on forced vital capacity (FVC) measurements. Providing complementary respiratory outcomes may be useful for ...clinical trials. Diaphragm sniff ultrasound (US) is a noninvasive technique that can assess diaphragm function that may be affected in patients with neuromuscular disorders.
We aimed to provide normal values of sniff diaphragm ultrasound, to assess the relationship between sniff diaphragm US, vital capacity (VC) and sniff nasal pressure. Additionally, we aimed to evaluate the diagnostic accuracy of sniff diaphragm US for predicting restrictive pulmonary insufficiency.
We included patients with neuromuscular disorders that had been tested with a sniff diaphragm US and functional respiratory tests. Healthy subjects were also included to obtain normal diaphragm sniff ultrasound. We performed diaphragm tissue Doppler imaging (TDI) and time movement (TM) diaphragm echography combined with sniff maneuver.
A total of 89 patients with neuromuscular diseases and 27 healthy subjects were included in our study. In patients, the median age was 32 years 25; 50 and the median FVC was 34% of predicted 18; 55. Sniff diaphragm motion using TM ultrasound was significantly associated with sniff nasal pressure, both for the right hemidiaphragm (r = 0.6 p <0.0001) and the left hemidiaphragm (r = 0.63 p = 0.0008). Right sniff peak TDI velocity was also significantly associated with FVC (r = 0.72, p<0.0001) and with sniff nasal pressure (r = 0.66 p<0.0001). Sniff diaphragm ultrasound using either TM mode or TDI displayed significant accuracy for predicting FVC<60% with an area under curve (AUC) reaching 0.93 (p<0.0001) for the right sniff diaphragm ultrasound in TM mode and 0.86 (p<0.001) for right peak diaphragm TDI velocity.
Sniff diaphragm TM and TDI measures were significantly associated with sniff nasal pressure. Sniff diaphragm TM and TDI had a high level of accuracy to reveal respiratory involvement in patients with neuromuscular disorders. This technique is useful to assess and follow up diaphragm function in patients with neuromuscular disorders. It may be used as a respiratory outcome for clinical trials.
Respiratory muscle strength is a proven predictor of long-term outcome of neuromuscular disease (NMD), including amyotrophic lateral sclerosis, Duchenne muscular dystrophy, and spinal muscular ...atrophy. Maximal inspiratory pressure (MIP), a sensitive measure of respiratory muscle strength, one of several useful tests of respiratory muscle strength, is gaining interest as a therapeutic clinical trial endpoint for NMD. In this comprehensive review we investigate the use of MIP as a measure of respiratory muscle strength in clinical trials of therapeutics targeting respiratory muscle, examine the correlation of MIP with survival, quality of life, and other measures of pulmonary function, and outline the role of MIP as a clinically significantly meaningful outcome measure. Our analysis supports the utility of MIP for the early evaluation of respiratory muscle strength, especially of the diaphragm, in patients with NMD and as a surrogate endpoint in clinical trials of therapies for NMD.
Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder caused by the absence of dystrophin, a sarcolemmal protein which links the cytoskeleton to the extracellular matrix by interacting ...with a large number of proteins. Heart failure is a classic complication of this disease. The authors review the pathogenesis and therapeutics of cardiac involvement in DMD.
Few studies have assessed the impact of home ventilation in patients with myotonic dystrophy type 1 (DM1) and no specific recommendations are available. We assessed the survival associated with ...category of home ventilation adherence of patients with DM1 followed up at a home ventilation unit using a Cox proportional hazards model. 218 patients were included; those who refused or delayed their acceptance of non-invasive ventilation were at higher risk for severe events (invasive ventilation or death) (P=0.03). Risk of death was associated with orthopnoea (HR 2.37; 95% CI 1.17 to 4.80; P<0.02) and adherence category (100 to 90% vs >75%: HR 3.26; 95% CI 1.32 to 8.04; P<0.03). Failure to use home ventilation as prescribed may be associated with increased mortality in patients with DM1.
Type 2C and 2D limb girdle muscular dystrophies (LGMD) are a group of autosomal recessive limb girdle muscular dystrophies manifested by proximal myopathy, impaired respiratory muscle function and ...cardiomyopathy. The correlation and the prognostic impact of respiratory and heart impairment are poorly described. We aimed to describe the long-term cardiac and respiratory follow-up of these patients and to determine predictive factors of cardio-respiratory events and mortality in LGMD 2C and 2D.
We reviewed the charts of 34 LGMD patients, followed from 2005 to 2015, to obtain echocardiographic, respiratory function and sleep recording data. We considered respiratory events (acute respiratory failure, pulmonary sepsis, atelectasis or pneumothorax), cardiac events (acute heart failure, significant cardiac arrhythmia or conduction block, ischemic stroke) and mortality as outcomes of interest for the present analysis.
A total of 21 patients had type 2C LGMD and 13 patients had type 2D. Median age was 30 years IQR 24-38. At baseline, median pulmonary vital capacity (VC) was 31% of predicted value 20-40. Median maximal inspiratory pressure (MIP) was 31 cmH2O IQR 20.25-39.75. Median maximal expiratory pressure (MEP) was 30 cm H2O 20-36. Median left ventricular ejection fraction (LVEF) was 55% 45-64 with 38% of patients with LVEF <50%. Over a median follow-up of 6 years, we observed 38% respiratory events, 14% cardiac events and 20% mortality. Among baseline characteristics, LVEF and left ventricular end diastolic diameter (LVEDD) were associated with mortality, whilst respiratory parameters (VC, MIP, MEP) and the need for home mechanical ventilation (HMV) were associated with respiratory events.
In our cohort of severely respiratory impaired type 2C and 2D LGMD, respiratory morbidity was high. Cardiac dysfunction was frequent in particular in LGMD 2C and had an impact on long-term mortality.
ClinicalTrials.gov NCT02501083.
Objective
Although several advantages are attributed to tracheotomy in ICU patients requiring mechanical ventilation (MV), true benefits and the optimal timing of tracheotomy remain controversial. In ...this study, we compared early tracheotomy (ET) with prolonged intubation (PI) in severely ill patients requiring prolonged MV.
Design
Prospective, randomized study.
Setting
Twenty-five medical and surgical ICUs in France.
Patients
Patients expected to require MV > 7 days.
Measurements and results
Patients were randomised to either (open or percutaneous) ET within 4 days or PI. The primary end-point was 28-day mortality. Secondary end-points were: the incidence of ICU-acquired pneumonia, number of d1-d28 ventilator-free days, time spent in the ICU, 60-day mortality, number of septic episodes, amount of sedation, comfort and laryngeal and tracheal complications. A sample size of 470 patients was considered necessary to obtain a reduction from 45 to 32% in 28-day mortality. After 30 months, 123 patients had been included (ET = 61, PI = 62) in 25 centres and the study was prematurely closed. All group characteristics were similar upon admission to ICU. No difference was found between the two groups for any of the primary or secondary end-points. Greater comfort was the sole benefit afforded by tracheotomy after subjective self-assessment by patients.
Conclusions
The trial did not demonstrate any major benefit of tracheotomy in a general population of ICU patients, as suggested in a previous meta-analysis, but was underpowered to draw any firm conclusions. The potential advantage of ET may be restricted to selected groups of patients.
Objective
To develop a population pharmacokinetic model for lopinavir boosted by ritonavir in coronavirus disease 2019 (Covid-19) patients.
Methods
Concentrations of lopinavir/ritonavir were assayed ...by an accredited LC-MS/MS method. The population pharmacokinetics of lopinavir was described using non-linear mixed-effects modeling (NONMEM version 7.4). After determination of the base model that better described the data set, the influence of covariates (age, body weight, height, body mass index (BMI), gender, creatinine, aspartate aminotransferase (AST), alanine aminotransferase (ALT), C reactive protein (CRP), and trough ritonavir concentrations) was tested on the model.
Results
From 13 hospitalized patients (4 females, 9 males, age = 64 ± 16 years), 70 lopinavir/ritonavir plasma concentrations were available for analysis. The data were best described by a one-compartment model with a first-order input (KA). Among the covariates tested on the PK parameters, only the ritonavir trough concentrations had a significant effect on CL/F and improved the fit. Model-based simulations with the final parameter estimates under a regimen lopinavir/ritonavir 400/100 mg b.i.d. showed a high variability with median concentration between 20 and 30 mg/L (
C
min
/
C
max
) and the 90% prediction intervals within the range 1–100 mg/L.
Conclusion
According to the estimated 50% effective concentration of lopinavir against SARS-CoV-2 virus in Vero E6 cells (16.7 mg/L), our model showed that at steady state, a dose of 400 mg b.i.d. led to 40% of patients below the minimum effective concentration while a dose of 1200 mg b.i.d. will reduce this proportion to 22%.
Respiratory involvement in neuromuscular disorders may contribute to impaired breathing-swallowing interactions, swallowing disorders and malnutrition. We investigated whether the use of non-invasive ...ventilation (NIV) controlled by the patient could improve swallowing performances in a population of neuromuscular patients requiring daytime NIV.
Ten neuromuscular patients with severe respiratory failure requiring extensive NIV use were studied while swallowing without and with NIV (while ventilated with a modified ventilator allowing the patient to withhold ventilation as desired). Breathing-swallowing interactions were investigated by chin electromyography, cervical piezoelectric sensor, nasal flow recording and inductive plethysmography. Two water-bolus sizes (5 and 10ml) and a textured yogurt bolus were tested in a random order.
NIV use significantly improved swallowing fragmentation (defined as the number of respiratory interruption of the swallowing of a single bolus) (p = 0.003) and breathing-swallowing synchronization (with a significant increase of swallows followed by an expiration) (p <0.0001). Patient exhibited piecemeal swallowing which was not influenced by NIV use (p = 0.07). NIV use also significantly reduced dyspnea during swallowing (p = 0.04) while preserving swallowing comfort, regardless of bolus type.
The use of patient controlled NIV improves swallowing parameters in patients with severe neuromuscular respiratory failure requiring daytime NIV, without impairing swallowing comfort.
ClinicalTrials.gov NCT01519388.
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