Interventional procedure overview of electrical stimulation of the pharynx for neurogenic dysphagia
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Summary of key evidence on electrical stimulation of the pharynx for neurogenic dysphagia
Study 1 Speyer R (2022)
Study type | Systematic review and meta-analysis |
|---|---|
Country | Not reported for individual studies |
Recruitment period | Not reported for individual studies |
Study population and number | n=10 studies, 428 people (252 active treatment), 5 studies were included in the meta-analysis People with neurogenic dysphagia. |
Age and sex | Mean 64.7 years; 56.7% male |
Patient selection criteria | Inclusion criteria:
Exclusion criteria: non-electrical peripheral stimulation (for example air-puff or gustatory stimulation), pharmacological interventions and acupuncture, invasive techniques and/or those that did not specifically target oropharyngeal dysphagia (for example, deep-brain stimulation studies after neurosurgical implementation of a neurostimulator), conference abstracts, doctoral theses, editorials, and reviews were excluded. |
Technique | PES. Typically delivered as 10-minute stimulation over 1 to 5 days (varying between studies). |
Follow up | Not reported for individual studies |
Conflict of interest/source of funding | Conflict of interest: The authors disclose no conflict of interest, however, 1 author is the co-founder of Phagenesis, the manufacturer of a PES device. Source of funding: No external funding was received. |
Analysis
Study design issues: This systematic review and meta-analysis assessed the efficacy of PES for people with oropharyngeal dysphagia. The methods and reporting of the systematic review were based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Study quality was assessed by the Cochrane Risk of Bias 2 (RoB 2) tool. The overall risk of bias for PES studies was assessed as 'low risk' for 6 studies and 'some concerns' for 4 studies. Five studies were included in the meta-analysis for PES, reasons for exclusion were given for 3 studies: overlap in population between studies, insufficient data for meta-analyses, and no confirmation of dysphagia diagnosis prior to treatment. It is not reported for which studies these reasons relate to.
Two meta-analyses were conducted to compare:
pre-post outcome measures of dysphagia.
mean difference between neurostimulation and comparison controls in outcome measures from pre- to post-intervention.
Effect sizes were calculated using a random-effects model were generated using the Hedges' g formula for standardised mean difference with a 95% CI. Effects sizes were interpreted using Cohen's d convention as follows: g ≤ 0.2 as no or negligible effect; 0.2 < g ≤ 0.5 as small effect; 0.5 < g ≤ 0.8 as moderate effect; and g > 0.8 as large effect. Heterogeneity was estimated using the Q statistic. I2-values of less than 50%, 50% to 74%, and higher than 75% denote low, moderate, and high heterogeneity, respectively. Publication bias was also assessed, and the authors concluded that there was no evidence of publication bias.
Study population issues: all studies included in the meta-analyses included people with post-stroke dysphagia.
Key efficacy findings
Pre-post meta-analysis
Number of people analysed: 5 studies
Five studies using PAS to assess dysphagia were included in the meta-analysis.
The pre-post intervention effect sizes for the included studies ranged from 0.265 (small effect) to 0.802 (large effect), with a statistically significant overall moderate effect size of 0.527 (z(4)=3.983, p=0.000, 95% CI 0.268 to 0.786) (Figure below).
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Between group meta-analysis
Number of people analysed: 5 studies
Five studies using PAS to assess dysphagia were included in the meta-analysis.
There was no statistically significant difference in PAS scores between PES and sham groups (z(4)=0.718, p=0.473, Hedges' g=0.099, and 95% CI -0.170 to 0.368), suggesting no improvement in PAS outcomes following PES neurostimulation versus sham (Figure below).
 |
Key safety findings
Safety findings were not reported.
Study 2 Cheng I (2021)
Study details
Study type | Systematic review and meta-analysis |
Country | Not reported for individual studies |
Recruitment period | Not reported for individual studies |
Study population and number | n=8 studies, 334 people (187 active treatment) People with post-stroke neurogenic dysphagia. |
Age and sex | Mean age of people in the studies ranged from 60.3 to 74.4; sex not reported |
Patient selection criteria | Inclusion criteria:
Exclusion criteria: Studies with people whose dysphagia was caused by other aetiologies, case studies, open-label studies, animal studies, observational studies, quasi-experimental studies, studies on healthy volunteers, studies that did not include original data, non-English studies. |
Technique | PES. 5 Hz, 75% tolerated threshold for 10 minutes over 1 or 3 days (varying between studies) |
Follow up | Perioperative to 3 months |
Conflict of interest/source of funding | Conflict of interest: Not reported, however, 1 author is the co-founder of Phagenesis, the manufacturer of a PES device. Source of funding: The authors declare no financial support. |
Analysis
Study design issues: This systematic review and meta-analysis assessed the efficacy of PES for people with post-stroke neurogenic dysphagia. The methods and reporting of the systematic review were based on the PRISMA statement. Study quality was assessed by the Cochrane RoB 2 tool. The authors note that there was insufficient information to determine the risk of selective reporting and other risks so these 2 aspects were not assessed. Most studies had low risk of bias in most aspects. The following studies were assessed as high risk of bias for the following domains: blinding of participants and personnel (Cabib, 2020; Jayasekeran, 2010; Vasant, 2016), incomplete outcome data (Bath, 2016). Three meta-analyses were conducted using PES studies:
Overall treatment effect vs. sham
Early (up to 2 weeks) effects vs. sham
Late (3 months or more) effects vs. sham
A weighted average of standardised mean difference across studies was computed using random effects model analysis. For the interpretation of effect sizes, standardised mean difference of 0.2 represented a small effect, 0.5 a moderate effect, and 0.8 a large effect. p<0.05 was considered statistically significant. Heterogeneity was assessed with Cochrane's Q statistic and I2 test in which heterogeneity was considered substantial with p<0.05 and I2 higher than 50%.
Key efficacy findings
Overall treatment effect meta-analysis
Number of people analysed: 8 studies
There was a statistically significant overall moderate effect size of PES compared to sham with substantial heterogeneity: SMD=0.68 (95% CI 0.22, 1.14; p=0.004; I2=65%) (Figure below).
As a sensitivity analysis, Bath, 2016 was removed from the analysis. This resulted in a statistically significant large effect size without substantial heterogeneity: SMD=0.83 (95% CI 0.43, 1.42; p<0.001; I2=34%).
 |
Early treatment effect meta-analysis
Number of people analysed: 8 studies
There was a statistically significant overall moderate effect size of PES compared to sham with substantial heterogeneity: SMD=0.68 (95% CI 0.22, 1.14; p=0.004; I2=65%) (Figure below).
 |
Late treatment effect meta-analysis
Number of people analysed: 2 studies
There was no statistically significant effect size of PES compared to sham with no heterogeneity: SMD=−0.04 (95% CI −0.46, 0.38; p=0.86; I2=0%) (Figure below).
 |
Key safety findings
Safety findings were not reported.
Study 3 Bath PM (2016)
Study details
Study type | Multicentre, double-blinded (patients, assessors), sham-controlled RCT |
Country | Denmark, France, Germany, Spain, and the UK |
Recruitment period | 2012 to 2014 |
Study population and number | n=162 (87 active treatment) People with recent stroke and videofluoroscopy-confirmed dysphagia |
Age and sex | Mean (all randomised) 74.0 years; 55.2% male |
Patient selection criteria | Inclusion criteria: people who were admitted to hospital with a clinical stroke syndrome because of ischemic or haemorrhagic stroke, were aged ≥18 years, had clinical dysphagia identified using bedside testing, were alert or rousable, had a PAS ≥3 for at least 1 swallow, and could be treated within 42 days of stroke onset. Exclusion criteria: a history of dysphagia, dysphagia from a condition other than stroke, advanced dementia, implanted pacemaker or cardiac defibrillator in situ, unstable cardiopulmonary status or a condition that compromised cardiac or respiratory status, distorted oropharyngeal anatomy, additional diagnosis of a progressive neurological disorder, receiving continuous oxygen treatment, or pregnant or nursing mother. |
Technique | PES with Phagenyx (Phagenesis, Ltd, Manchester, UK). Electric current at 5 Hz was administered for 10 minutes each day for 3 days. The current of the stimulation was calculated as the threshold current (the current at which the patient can first detect stimulation) plus 75% of the difference between threshold and tolerance current (the current at which the patient does not want the current increased further). The mean treatment stimulation level was 14.5 mA in those randomised to PES. |
Follow up | 12 weeks |
Conflict of interest/source of funding | Conflict of interest: The lead author received honoraria for work as the chief investigator and for consultancy. One author is the co-founder of Phagenesis, the manufacturer of a PES device. One author was an employee of Phagenesis. Source of funding: The trial was sponsored and funded by Phagenesis, the manufacturer of a PES device. |
Analysis
Follow up issues: Of 162 people who were randomised, treatment was attempted in 152 (safety population), 141 were treated (with at least 1 session of PES or sham), videofluoroscopy was obtained in 126 at 2 weeks (primary outcome population), and in 95 at 12 weeks.
Study design issues: This RCT assessed the efficacy and safety of PES to treat post-stroke dysphagia. Patients with recent stroke and confirmed dysphagia were randomised 1:1 to PES or sham. The sample size was based on statistical power calculations such that the trial had 90% power to detect a difference of 1.1 points on the PAS at a 2-sided significance level of 5%. Patients and outcome assessors were blinded to treatment allocation, treating researchers were unblinded. Patients randomised to sham therapy had no stimulation after establishment of threshold and tolerated levels of current. This determination of threshold and tolerated levels of current may have inadvertently exposed sham patients to therapeutic stimulation. As patients could feel the effects of treatment, or the absence of treatment with sham, some patients may have become prematurely unblinded to treatment allocation. The authors also reported that there was evidence of suboptimal treatment, with 58% of PES-treated patients had a treatment level less than 10.2 mA (a figure chosen from earlier research), identical treatment and threshold levels, or a treatment level less than threshold.
The outcomes included:
Primary: PAS at 2 weeks
Secondary: PAS at 12 weeks, DSRS, modified Rankin Scale, Barthel Index, NIHSS, HRQoL, and nutritional measures.
The primary outcome was analysed using multiple linear regression. Secondary outcomes were analysed using multiple linear regression (for continuous outcomes), ordinal logistic regression (ordered categorical data), binary logistic regression (dichotomous data), and Kaplan–Meier and Cox regression models (time to event). There was no adjustment for multiple comparisons reported.
Study population issues: No statistical analysis was performed, but the authors reported that the PES and sham groups were 'well balanced at baseline'. Some select baseline characteristics follow. Most people were white (85.8%), with smaller numbers of Asian (9.3%), black (2.5%), and 'other' (2.5%) people. Stroke types were ischaemic/normal (88.8%) and intracerebral haemorrhage (10.6%). The mean time from stroke to randomisation was 13 days.
Key efficacy findings
PAS
Number of people analysed: 126
There were no statistically significant differences in the change from baseline to 2 weeks in PAS scores between the PES and sham groups (mean difference=0.14; 95% CI -0.37 to 0.64; p=0.60).
There was also no statistically significant difference in the proportion of people who had any PAS >3 between the PES and sham groups (85.7% vs. 80.4%, p=0.79).
At 12 weeks, there was no statistically significant difference in the mean PAS scores between the PES and sham groups (mean difference=0.29; 95% CI −0.04 to 0.99; p=0.41).
There were no statistically significant interactions observed in subgroup analysis.
All (N=126) | PES (N=70) | Sham (N=56) | OR/MD (95% CI), Adjusted | p | OR/MD (95% CI), Unadjusted | p | |
Baseline | |||||||
PAS (/8) | 4.8 (2.0) | 4.8 (2.1) | 4.7 (1.9) | - | - | - | - |
2 week primary outcome | |||||||
Mean of all boli (/8) | 3.6 (2.0) | 3.7 (2.0) | 3.6 (1.9) | 0.14 (−0.37 to 0.64) | 0.60 | 0.06 (−0.62 to 0.74) | 0.86 |
Change from baseline | −1.2 (1.8) | −1.2 (1.8) | −1.2 (1.8) | 0.14 (−0.37 to 0.64) | 0.60 | 0.00 (−0.62 to 0.61) | 1.00 |
Any PAS >3 (%) | 105 (83.3) | 60 (85.7) | 45 (80.4) | 1.22 (0.29 to 5.15) | 0.79 | 1.47 (0.57 to 3.75) | 0.42 |
12 week | |||||||
Mean of all boli (/8) | 3.2 (2.1) | 3.3 (2.2) | 3.0 (2.1) | 0.29 (−0.04 to 0.99) | 0.41 | 0.24 (−0.6 to 1.08) | 0.57 |
Any PAS >3 (%) | 69 (72.6) | 36 (70.6) | 33 (75.0) | 0.62 (0.20 to 1.90) | 0.41 | 0.80 (0.32 to 1.99) | 0.63 |
Repeated measures | |||||||
Mean (/8)* | - | 4.1 (2.3) | 3.9 (2.3) | 0.51 (−0.23 to 1.25) | 0.18 | 0.19 (−0.67 to 1.04) | 0.67 |
All patients had diagnostic videofluoroscopy at both baseline and 2 weeks and received at least 1 treatment session. Data are number (%), median (interquartile range), or mean (SD), with comparisons using unadjusted and adjusted multiple linear, ordinal logistic, or binary logistic regression. CI, confidence interval; MD, mean difference; OR, odds ratio; PAS, penetration aspiration score; PES, pharyngeal electric stimulation.
*Includes death: PAS=9.
Secondary outcomes
Number of people analysed: various, see table.
There were no statistically significant differences between the PES and sham groups in any of the secondary outcomes assessed.
N | All | PES | Sham | OR/HR/MD (95% CI), Unadjusted | p | OR/HR/MD (95% CI), Unadjusted | p | |
2 week | ||||||||
DSRS (/12)* | 133 | 5.1 (3.8) | 5.2 (4.1) | 4.9 (3.6) | 0.31 (−0.56 to 1.18) | 0.49 | 0.23 (−1.07 to 1.54) | 0.72 |
NIHSS (/42)* | 134 | 9.6 (7.2) | 9.0 (7.4) | 10.2 (7.1) | −0.05 (−1.42 to 1.32) | 0.94 | −1.19 (−3.64 to 1.26) | 0.34 |
mRS (/6)* | 134 | 3.9 (1.1) | 3.7 (1.2) | 4.1 (1.0) | 0.53 (0.23 to 1.22) | 0.14 | 0.49 (0.26 to 0.92) | 0.028 |
BI (/100)* | 134 | 36.2 (34.9) | 41.3 (37.2) | 29.8 (31.0) | 1.57 (−3.60 to 6.73) | 0.55 | 11.45 (−0.22 to 23.13) | 0.055 |
Death (%) | 141 | 2 (1.4) | 1 (1.3) | 1 (1.6) | … | … | 0.81 (0.05 to 13.13) | 0.88 |
12 week | ||||||||
DSRS (/12)* | 124 | 4.2 (5.1) | 4.4 (5.2) | 3.9 (5.1) | 1.01 (−0.44 to 2.46) | 0.17 | 0.58 (−1.23 to 2.39) | 0.53 |
EQ-5D as HUS (/1)* | 113 | 0.02 (0.40) | 0.08 (0.41) | −0.04 (0.39) | 0.13 (0.00 to 0.27) | 0.054 | 0.12 (−0.03 to 0.27) | 0.11 |
EQ-VAS* | 105 | 50.3 (30.7) | 51.6 (30.1) | 48.6 (31.7) | −4.17 (−15.22 to 6.88) | 0.46 | 3.03 (−8.70 to 14.76) | 0.61 |
Disposition (%) | 141 | 0.66 (0.30 to 1.49) | 0.32 | 0.63 (0.31 to 1.26) | 0.19 | |||
Home | 30 (21.3) | 20 (25.6) | 10 (15.9) | … | … | … | … | |
Institution | 93 (66.0) | 49 (62.8) | 44 (69.8) | … | … | … | … | |
Died | 18 (12.8) | 9 (11.5) | 9 (14.3) | … | … | … | … | |
Time to event | ||||||||
Discharge (days) | 141 | 28.2 (22.8) | 27.7 (22.7) | 28.7 (23.0) | −0.33 (−7.79 to 7.12) | 0.93 | −0.97 (−9.72 to 7.78) | 0.83 |
Death (%) | 141 | 18 (12.8) | 9 (11.5) | 9 (14.3) | 1.11 (0.34 to 3.59) | 0.86 | 0.79 (0.32 to 2.00) | 0.62 |
BI, Barthel Index; DSRS, dysphagia severity rating scale; EQ-5D, European Quality of Life-5 Dimensions; EQ-VAS, European Quality of Life Visual Analogue Scale; HR, hazard ratio; HUS, health utility status; MD, mean difference; mRS, modified Rankin Scale; NIHSS, National Institutes of Health Stroke Scale; OR, odds ratio; and PES, pharyngeal electric stimulation.
*Includes death: NIHSS=43, DSRS=13, mRS=6, BI=−5, and HUS=0.
Key safety findings
Number of people analysed: 152
There was no statistically significant difference in the rate of SAEs at the end of follow up: Total n=40 (26.3%), PES n=22 (25.9%), sham n=18 (26.9%) (p=1.00).
No SADEs occurred in either group.
Any | Fatal | |||||||
All | PES | Sham | p | All | PES | Sham | p | |
Patients | 152 | 85 | 67 | 152 | 85 | 67 | ||
Cardiac | 9 (5.9) | 6 (7.1) | 3 (4.5) | 0.73 | 4 (2.6) | 2 (2.4) | 2 (3.0) | 1.00 |
Gastrointestinal | 2 (1.3) | 2 (2.4) | 0 (0) | 0.50 | 0 (0) | 0 (0) | 0 (0) | - |
General | 3 (2.0) | 0 (0) | 3 (4.5) | 0.083 | 3 (2.0) | 0 (0) | 3 (4.5) | 0.083 |
Hepatobiliary | 1 (0.7) | 1 (1.2) | 0 (0) | 1.00 | 0 (0) | 0 (0) | 0 (0) | - |
Infections | 11 (7.2) | 6 (7.1) | 5 (7.5) | 1.00 | 4 (2.6) | 2 (2.4) | 2 (3.0) | 1.00 |
Investigations | 1 (0.7) | 1 (1.2) | 0 (0) | 1.00 | 0 (0) | 0 (0) | 0 (0) | - |
Neoplasms | 1 (0.7) | 1 (1.2) | 0 (0) | 1.00 | 1 (0.7) | 1 (1.2) | 0 (0) | 1.00 |
Nervous system | 8 (5.3) | 4 (4.7) | 4 (6.0) | 0.73 | 4 (2.6) | 3 (3.5) | 1 (1.5) | 0.63 |
Renal/urinary | 2 (1.3) | 1 (1.2) | 1 (1.5) | 1.00 | 0 (0) | 0 (0) | 0 (0) | - |
Respiratory | 8 (5.3) | 5 (5.9) | 3 (4.5) | 1.00 | 2 (1.3) | 1 (1.2) | 1 (1.5) | 1.00 |
Surgical/medical | 2 (1.3) | 2 (2.4) | 0 (0) | 0.50 | 0 (0) | 0 (0) | 0 (0) | - |
Total SAEs | 40 (26.3) | 22 (25.9) | 18 (26.9) | 1.00 | 18 (11.8) | 9 (10.6) | 9 (13.4) | 0.62 |
Total SADEs | 0 (0) | 0 (0) | 0 (0) | - | 0 (0) | 0 (0) | 0 (0) | - |
PES, pharyngeal electrical stimulation; SADE, serious adverse device-related event; SAE, serious adverse event.
Study details
Study type | Multicentre, double-blinded (patients, assessors), sham-controlled RCT followed by open-label crossover period |
Country | Austria, Germany, Italy |
Recruitment period | 2015 to 2017 |
Study population and number | n=69 (35 active treatment) People with recent stroke and dysphagia who required tracheotomy. |
Age and sex | Mean 64 years; 64% male |
Patient selection criteria | Inclusion criteria: supratentorial stroke (haemorrhagic or ischaemic), mechanically ventilated for at least 48 hours post-stroke, successfully weaned from mechanical ventilation but remained tracheotomised, free of sedation for at least 3 days at the time of first decannulation screening, scored -1 or more points on the Richmond Agitation and Sedation Scale, and could not be decannulated due to severe dysphagia. Exclusion criteria: infratentorial stroke, pre-existing dysphagia, pre-existing disease that typically causes dysphagia (for example Parkinson's disease), participation in any other study potentially influencing the outcome of PES, presence of a cardiac pacemaker or an implantable defibrillator, nasal deformity or previous oesophageal surgery or any other circumstance where placement of a standard nasogastric tube would be deemed unsafe, need for high levels of oxygen supply (more than 2 l/min), required emergency treatment, or had less than 3 months life expectancy. |
Technique | PES with Phagenyx (Phagenesis, Ltd, Manchester, UK). Electric current at 5 Hz was administered for 10 minutes each day for 3 days. The current of the stimulation was calculated as the threshold current (the current at which the patient can first detect stimulation) plus 75% of the difference between threshold and tolerance current (the current at which the patient does not want the current increased further). The mean treatment stimulation level was 33.6 mA in those randomised to PES. |
Follow up | 90 days |
Conflict of interest/source of funding | Conflict of interest: One author is the co-founder of Phagenesis, the manufacturer of a PES device. Other authors report fees from Phagenesis for travel, training, and payments per-patient for the study conduct, amongst others. Source of funding: Funded by Phagenesis, the manufacturer of a PES device. |
Analysis
Follow up issues: Of 69 people randomised, 68 had day 2 data, 65 had day 30 or hospital discharge data, and 52 had day 90 data.
Study design issues: This RCT assessed the efficacy and safety of PES for early decannulation of people who had post-stroke dysphagia. Patients were randomised 1:1 to PES or sham and received 3 days of treatment. Readiness for decannulation was assessed 24 to 72 hours after the final stimulation. Those who remained cannulated could then enter an open-label phase. The maximum sample size was set at 140 people to detect an absolute difference between the groups of 25%, assuming that the control rate would be 20%, significance level of 0.05, and power 0.80. Predetermined interim analyses were performed when recruitment reached 50 patients, 70 patients, and every 10 patients after. At the 70-patient interim analysis, the study was stopped for superiority. Patients and outcome assessors were blinded to treatment allocation, treating researchers were unblinded. As patients could feel the effects of treatment, or the absence of treatment with sham, some patients may have become prematurely unblinded to treatment allocation.
The outcomes included:
Primary: readiness for decannulation 24 to 72 hours after 3 days of PES
The presence of massive pooling of saliva, limited spontaneous swallows (less than 1 per minute), and/or no sensation elicited by endoscope contact with the laryngeal vestibule meant that patients were not ready for decannulation.
Secondary: treatment effect in delayed and retreated patients, necessity of recannulations (at day 2 and during follow-up of 30 days or until discharge, whichever is first), dysphagia scores (DSRS, FOIS), severity of stroke (modified Rankin Scale and National Institutes of Health Stroke Scale scores) (at day 2, during follow-up of 30 days or until discharge, whichever was first), length of stay on different levels of care, Speech and Language Therapy management plan, number and type of AEs, including adverse device-related events.
Outcomes were analysed using Fisher's exact test for binary data, Mann-Whitney-U test for ordinal data, and Student's t-test (pooled) for continuous data. Regressions were performed using binary logistic regression, Cox regression and multiple linear regression. p<0.05 was considered statistically significant. No adjustment was made for multiple comparisons, and all analyses were by intention to treat.
Study population issues: No statistically significant differences in baseline characteristics were reported between the treatment groups. Overall, 49 (71%) patients had an ischemic stroke, and 20 (29%) an intracerebral haemorrhage. The median time from stroke to randomisation was 28 days.
Key efficacy findings
Decannulation
Number of people analysed: 69
In the primary outcome, there was a higher likelihood of readiness for decannulation 24 to 72 hours after treatment with PES compared to sham, OR: 7.00 (95% CI 2.41 to 19.88, p=0.00082).
No patients who had decannulation performed required re-cannulation over the next 48 hours, or during their documented follow-up period up to hospital discharge.
Based on these outcome data, the study was stopped for superiority by an Independent Data and Safety Monitoring Board.
In predefined subgroups, statistically significant treatment-by-subgroup interactions were present, these favouring treatment in patients treated earlier after stroke, or with a shorter duration of mechanical ventilation.
Considering both the randomised and open-label parts of the study, a total of 57% of the patients became ready for decannulation 24 to 72 hours after PES.
Total | PES | Sham | OR (95% CI) | p | |
Randomised part 1 of the study | |||||
Patients | 69 | 35 | 34 | ||
Ready for decannulation after PES/Sham (%) (Primary outcome) | 17 (49) | 3 (9) | 7.00 (2.41-19.88) | 0.00082 | |
Removal of the tracheal tube (%)* | 14 (82) | 1 (33) | 9.33 (0.62-139.57) | 0.1404 | |
Deflation of the tube-cuff (%)* | 3 (18) | 1 (33) | 0.43 (0.03-6.41) | 0.5088 | |
Open-label part 2 of the study | |||||
Patients | 45 | 15 | 30 | ||
Ready for decannulation" after open-label treatment** (%) | 20 (44) | 4 (27) | 16 (53) | 0.32 (0.08-1.23) | 0.1185 |
Removal of the tracheal tube (%)* | 17 (38) | 3 (20) | 14 (47) | 0.29 (0.07-1.22) | 0.1097 |
Deflation of the tube-cuff (%)* | 3 (7) | 1 (7) | 2 (7) | 1.00 (0.08-12.00) | 1.0000 |
Re-cannulation within 48 hrs (%) | 0 (0) | 0 (0) | - | - | |
Re-cannulation within 30 days or hospital discharge (whichever is first) (%) | 0 (0) | 0 (0) | - | - |
OR, odds ratio; PES: pharyngeal electrical stimulation.
*Statistical comparison within the subgroup of patients reaching the primary endpoint.
**These are data related only to the open label part of the study where all non-responders were given PES.
One patient in the PES group had a non-treatment-related adverse event occurring prior to third day of PES which required transfer to another hospital for surgery; as a result, assessment was not possible. Conservatively, the patient was assigned to no decannulation.
Secondary outcomes
Number of people analysed: Various, see table
There were no differences between the groups in secondary outcomes.
Total | PES | Sham | OR/MD (95% CI) | p | |
DSRS, N, mean (SD) | |||||
Baseline | 12 (0) | 12 (0) | |||
Day 2 | 60 | 30, 10.6 (2.4) | 30, 10.4 (2.7) | 0.27 (-1.05, 1.59) | 0.6873 |
Day 30 or Hospital Discharge (whichever is first) | 50 | 25, 8.0 (4.6) | 25, 8.9 (3.3) | -0.88 (-3.17, 1.41) | 0.4437 |
Day 90 | 53 | 27, 4.6 (5.3) | 26, 5.7 (5.1) | -1.10 (-3.97, 1.77) | 0.4449 |
FOIS, N, mean (SD) | |||||
Baseline | 1 (0) | 1 (0) | |||
Day 2 | 61 | 31, 1.7 (1.2) | 30, 1.9 (1.4) | -0.191 (-0.878, 0.495) | 0.5789 |
Day 30 or Hospital Discharge (whichever is first) | 50 | 25, 3.0 (2.4) | 25, 2.5 (1.7) | 0.560 (-0.61, 1.73) | 0.3407 |
Day 90 | 53 | 27, 4.6 (2.6) | 26, 3.9 (2.5) | 0.745 (-0.660, 2.150) | 0.2922 |
NIHSS, N, mean (SD) | |||||
Baseline | 68 | 34, 17.6 (5.0) | 34, 17.5 (4.3) | 0.118 (-2.129, 2.364) | 0.9170 |
Day 2 | 47 | 24, 15.6 (4.5) | 23, 15.7 (6.4) | -0.027 (-3.287, 3.233) | 0.9867 |
Day 30 or Hospital Discharge (whichever is first) | 48 | 24, 14.0 (5.0) | 24, 13.8 (5.9) | 0.292 (-2.865, 3.448) | 0.8533 |
Day 90 | 16 | 8, 10.1 (9.2) | 8, 16.9 (8.6) | -6.750 (-16.281, 2.781) | 0.1510 |
mRS, N, mean (SD) | |||||
Baseline | 68 | 34, 5.0 (0.0) | 34, 5.0 (0.2) | 0.029 (-0.029, 0.088) | 0.3210 |
Day 2 | 61 | 31, 4.6 (1.3) | 30, 4.6 (1.3) | 0.078 (-0.570, 0.727) | 0.8094 |
Day 30 or Hospital Discharge (whichever is first) | 54 | 28, 4.8 (0.5) | 26, 4.7 (0.5) | 0.091 (-0.163, 0.345) | 0.4769 |
Day 90 | 51 | 26, 4.1 (0.8) | 25, 4.3 (1.0) | -0.203 (-0.730, 0.324) | 0.4421 |
Level of care | |||||
Baseline | |||||
Patients | 65 | 32 | 33 | ||
Intensive Care Unit | 8 (25) | 7 (21) | 1.24 (0.39-3.93) | 0.7746 | |
Intermediate Care Unit | 21 (66) | 23 (70) | 0.83 (0.29-2.35) | 0.7944 | |
Normal ward | 3 (10) | 3 (10) | 1.03 (0.19-5.55) | 1.0000 | |
Day 2 | |||||
Patients | 50 | 25 | 25 | ||
Intensive Care Unit | 3 (12) | 1 (4) | 3.27 (0.32-33.84) | 0.6092 | |
Intermediate Care Unit | 15 (60) | 16 (64) | 0.84 (0.27-2.65) | 1.0000 | |
Normal ward | 7 (28) | 8 (32) | 0.83 (0.25-2.78) | 1.0000 | |
Day 10 | |||||
Patients | 24 | 13 | 11 | ||
Intensive Care Unit | 2 (15) | 1 (9) | 1.82 (0.14-23.25) | 1.0000 | |
Intermediate Care Unit | 4 (31) | 5 (46) | 0.53 (0.10-2.84) | 0.6752 | |
Normal ward | 7 (54) | 5 (46) | 1.40 (0.28-7.02) | 1.0000 | |
Day 30 | |||||
Patients | 14 | 7 | 7 | ||
Intensive Care Unit | 0 (0) | 0 (0) | - | - | |
Intermediate Care Unit | 2 (29) | 1 (14) | 2.40 (0.16-34.93) | 1.0000 | |
Normal ward | 5 (71) | 6 (86) | 0.42 (0.03-6.06) | 1.0000 |
DSRS: dysphagia severity rating scale; FOIS: functional oral intake scale; NIHSS: National Institute of Health Stroke Scale; MD, mean difference; mRS: modified Rankin Scale; OR, odds ratio; PES: pharyngeal electrical stimulation.
Key safety findings
Number of people analysed: 69
A total of 7 people in the PES group (20%), 3 people in the sham group (9%) and 1 person prior to randomisation (8%) died during the study.
None of the deaths were judged to be PES-treatment or investigational device- (base station and catheter) related by the Independent Data and Safety Monitoring Board.
There was no statistically significant difference between the number of people with at least 1 SAE in the treatment groups.
A total of 12 non-serious device-related adverse events were observed in 8 different people.
Data are number of events (number of patients [%]) | PES | Sham | Non-randomised** |
SAEs: | |||
Prior randomisation* | 1 (1 [3%]) | 1 (1 [3%]) | 3 (2 [17%]) |
0-1 month after randomisation | 3 (3 [9%]) | 4 (4 [12%]) | |
1-3 months after randomisation | 8 (7 [20%]) | 4 (1 [3%]) | |
Total study | 12 (10 [29%]) | 9 (8 [24%]) | 3 (2 [17%]) |
Most commonly observed SAEs (3 or more events) | |||
Pneumonia | 2 (2 [6%]) | 1 (1 [3%]) | |
Cardiac Arrest | 2 (2 [6%]) | 1 (1 [3%]) | |
Sepsis | 3 (3 [9%]) | 4 (4 [12%]) | |
Hydrocephalus | 2 (2 [6%]) | 0 | 1 (1 [8%]) |
Death | 7 (7 [20%]) | 3 (3 [9%]) | 1 (1 [8%]) |
AEs (non-serious) | 55 (21 [60%]) | 50 (21 [62%]) | 0 |
Most commonly observed AEs (3 or more events) | |||
Diarrhoea | 2 (2 [6%]) | 4 (4 [12%]) | |
Vomiting | 6 (4 [11%]) | 6 (2 [6%]) | |
Pneumonia | 3 (3 [9%]) | 6 (5 [15%]) | |
Urinary Tract Infection | 8 (7 [20%]) | 3 (3 [9%]) | |
Infection (Other) | 6 (6 [17%]) | 4 (3 [9%]) | |
Musculoskeletal Pain | 3 (2 [6%]) | 0 | |
Hypoxia | 2 (2 [6%]) | 1 (1 [3%]) | |
Thrombophlebitis | 2 (2 [6%]) | 1 (1 [3%]) | |
Adverse Device-related Events (ADEs) | 8 (5 [14%]) | 4 (3 [9%]) | |
Most commonly observed ADEs (3 or more events) | |||
Medical Device Complication | 6 (5 [14%]) | 3 (2 [6%]) | |
Serious ADEs (SADEs) | 0 | 0 |
*Prior randomisation is defined as period from date of informed consent to date of randomisation.
**Non-randomised is defined as patients who were never ultimately randomised.
Study details
Study type | Multicentre, prospective registry analysis (the PHAryngeal electrical stimulation for treatment of neurogenic Dysphagia European Registry [PHADER]) |
Country | Austria, Germany, UK |
Recruitment period | 2015 to 2018 |
Study population and number | n=252 People with dysphagia due to stroke, traumatic brain injury, or any other neurological cause. |
Age and sex | Mean 68.2; 70.6% male |
Patient selection criteria | Inclusion criteria: oropharyngeal dysphagia with a DSRS score of 6 or higher, and belonged to one of the following diagnostic groups: dysphagia related to (A) stroke not requiring mechanical ventilation; (B) stroke requiring mechanical ventilation and tracheotomy; (C) mechanical ventilation in non-stroke, non-TBI; (D) TBI with or without the need for mechanical ventilation and tracheotomy; and (E) any other neurological cause not needing mechanical ventilation and tracheotomy. Exclusion criteria: non-neurogenic dysphagia (for example, cancer), presence of an implanted cardiac pacemaker or cardioverter defibrillator, pregnancy or a nursing mother. |
Technique | PES with Phagenyx (Phagenesis, Ltd, Manchester, UK). Electric current at 5 Hz was administered for 10 minutes each day for 3 days. The current of the stimulation was calculated as the threshold current (the current at which the patient can first detect stimulation) plus 75% of the difference between threshold and tolerance current (the current at which the patient does not want the current increased further). The mean treatment stimulation level was approximately 28 mA across the 3 treatment sessions. |
Follow up | 3 months |
Conflict of interest/source of funding | Conflict of interest: One author is the co-founder of Phagenesis, the manufacturer of a PES device. Two further authors are employees of Phagenesis. Other authors report grants from various government, charity, and industry sources. Source of funding: Funded and sponsored by Phagenesis Ltd., the manufacturer of a PES device. Sites were compensated for data collection. |
Analysis
Follow up issues: Of 252 people enrolled, 245 were included in the analysis (7 excluded due to lack or withdrawal of consent, spontaneous recovery or unavailability of a catheter or death), 232 had day 2 follow-up data, 210 had day 30 data, and 190 had day 92 data.
Study design issues: This multicentre, prospective study analysed the efficacy and safety of PES for neurogenic dysphagia in people enrolled in the PHADER registry. This study was reported to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement. Outcomes included:
Primary: DSRS score at 3 months post-treatment
Secondary: dysphagia severity assessed using the FOIS and penetration-aspiration assessed with the PAS measured instrumentally (using videofluoroscopy or fibreoptic endoscopic evaluation of swallowing).
Sample size was set at 60 people per diagnostic group so that the presence of a device deficiency in 5% of the population could be ruled out with confidence of 80% (lower recruitment was expected in groups C, D, and E). Statistical analyses were conducted by intention to treat. A variety of statistical tests were used to analyse the data. No imputation was performed for missing data, and no adjustment was made for multiple comparisons. p<0.05 was considered statistically significant.
Study population issues: By diagnostic group, 84 people had an index stroke not requiring mechanical ventilation (group A); 99 had an index stroke requiring mechanical ventilation and tracheotomy (group B); 35 had dysphagia related to a non-stroke/non-TBI cause (group C) with 15 of these due to critical illness polyneuropathy; 24 had a TBI (group D); and 3 had another cause for their dysphagia (group E). The median time from onset of dysphagia to treatment was 32.0 days. There were statistically significant differences in the median time from onset of dysphagia to treatment in the subgroups (from stroke, not ventilated=16.0 days; to other neurological causes=169.0 days).
Key efficacy findings
Primary outcome
Number of people analysed: various, see table
There was a statistically significant decrease in DSRS score in the overall population from 11.4 at baseline to 5.1 on day 92 after PES (mean difference=-6.3, p<0.001).
All subpopulations saw similar statistically significant decreases in DSRS scores after PES.
All | Stroke, not ventilated | Stroke, ventilated | Ventilator-related | TBI | p | |
DSRS (/12) | ||||||
Baseline | 236, 11.4 (1.7) | 79, 10.9 (2.4) | 98, 11.7 (1.2) | 35, 11.9 (0.5) | 24, 11.3 (1.8) | 0.003 |
Day 5 | 229, 10.5 (2.6) | 74, 9.9 (2.9) | 97, 10.8 (2.4) | 35, 10.8 (2.5) | 23, 11.0 (2.5) | |
Day 9 | 224, 8.6 (3.9) | 70, 7.7 (4.1) | 97, 8.9 (3.8) | 35, 8.5 (4.1) | 22, 10.4 (3.1) | |
Day 92 | 174, 5.1 (4.9) | 46, 4.2 (4.2) | 78, 5.2 (5.0) | 30, 5.3 (5.4) | 20, 6.8 (4.8) | 0.26 |
DIM (unpaired) | ‑6.3 (‑7.0, ‑5.6)* | ‑6.7 (‑7.8, ‑5.5)* | ‑6.5 (‑7.6, ‑5.5)* | ‑6.6 (‑8.4, ‑4.8)* | ‑4.5 (‑6.6, ‑2.4)* | 0.31 |
MD (paired) | 174, ‑6.3 (‑7.0, ‑5.6)* | 46, ‑6.5 (‑7.9, ‑5.2)* | 78, ‑6.5 (‑7.6, ‑5.3)* | 30, ‑6.6 (‑8.5, ‑4.6)* | 20, ‑4.7 (‑6.8, ‑2.5)* | 0.033 |
*p<0.001
Data are number of participants, mean (standard deviation), difference in means and mean difference
(95% confidence interval); comparison of groups by analysis of variance, and day 92 versus baseline by paired and unpaired t-tests.
Secondary outcomes
Number of people analysed: various, see table
There was a statistically significant increase in FOIS score in the overall population from 1.4 at baseline to 4.3 on day 92 after PES (mean difference=2.9, p<0.001).
All subpopulations except TBI saw similar statistically significant increase in FOIS scores after PES.
There was a statistically significant decrease in PAS score in the overall population from 6.7 at baseline to 3.2 on day 92 after PES (mean difference=-4.1, p<0.001).
All subpopulations except TBI saw similar statistically significant decrease in PAS scores after PES.
All | Stroke, not ventilated | Stroke, ventilated | Ventilator-related | TBI | p | |
FOIS (/7) | ||||||
Baseline | 220, 1.4 (0.9) | 65, 1.7 (1.3) | 97, 1.2 (0.6) | 34, 1.1 (0.3) | 24, 1.4 (0.7) | <0.001 |
Day 5 | 214, 1.8 (1.4) | 63, 2.2 (1.5) | 96, 1.8 (1.3) | 32, 1.8 (1.4) | 23, 1.5 (1.0) | |
Day 9 | 213, 2.7 (1.9) | 61, 3.2 (1.9) | 96, 2.5 (1.9) | 34, 3.0 (2.1) | 22, 1.9 (1.5) | |
Day 92 | 172, 4.3 (2.5) | 42, 4.5 (2.3) | 79, 4.3 (2.6) | 31, 4.4 (2.7) | 20, 3.4 (2.4) | 0.38 |
DIM (unpaired) | 2.9 (2.5, 3.3)* | 2.8 (2.1, 3.5)* | 3.1 (2.5, 3.6)* | 3.3 (2.4, 4.3)* | 2.0 (1.0, 3.0) | 0.20 |
MD (paired) | 170, 2.9 (2.5, 3.3)* | 40, 2.8 (2.0, 3.5)* | 79, 3.1 (2.5, 3.7)* | 31, 3.3 (2.3, 4.3)* | 20, 2.0 (0.9, 3.0) | 0.042 |
PAS (/8) | ||||||
Baseline | 144, 6.7 (1.7) | 42, 6.2 (1.7) | 53, 7.2 (1.2) | 27, 6.8 (1.6) | 22, 6.5 (2.4) | 0.031 |
Day 5 | 89, 5.2 (2.5) | 19, 4.3 (2.5) | 39, 5.4 (2.4) | 18, 4.9 (2.8) | 13, 6.1 (2.4) | |
Day 9 | 100, 4.4 (2.7) | 21, 3.8 (2.6) | 44, 4.3 (2.7) | 20, 3.6 (2.7) | 15, 6.7 (1.9) | |
Day 92 | 68, 3.2 (2.6) | 10, 2.8 (2.1) | 31, 3.0 (2.6) | 15, 2.2 (2.0) | 12, 5.3 (2.7) | 0.011 |
DIM (unpaired) | -3.5 (-4.1, -2.9)* | -3.4 (-4.7, -2.1)* | -4.2 (-5.0, -3.3)* | -4.6 (-5.8, -3.5)* | -1.2 (-3.0, 0.6) | 0.003 |
MD (paired) | 68, -4.1 (-4.8, -3.3)* | 10, -3.8 (-6.3, -1.3) | 31, -4.5 (-5.5, -3.4)* | 15, -5.3 (-6.5, -4.1)* | 12, -1.7 (-3.6, 0.3) | |
Discharge disposition | 0.001 | |||||
Acute care | 16 (11.2) | 3 (5.0) | 10 (18.9) | 1 (5.9) | 2 (18.2) | |
Sub-acute care | 40 (28.0) | 9 (15.0) | 26 (49.1) | 4 (23.5) | 1 (9.1) | |
Assisted care | 6 (4.2) | 5 (8.3) | 0 (0.0) | 0 (0.0) | 1 (9.1) | |
Full-nursing care | 11 (7.7) | 6 (10.0) | 3 (5.7) | 1 (5.9) | 1 (9.1) | |
Home care | 44 (30.8) | 22 (36.7) | 7 (13.2) | 9 (52.9) | 4 (36.4) | |
Death | 26 (18.2) | 15 (25.0) | 7 (13.2) | 2 (11.8) | 2 (18.2) | |
*p<0.001
Data are number of participants, mean (standard deviation), difference in means and mean difference
(95% confidence interval); comparison of groups by analysis of variance, and day 92 versus baseline by paired and unpaired t-tests.
Key safety findings
Number of people analysed: 245
SAEs: 74 SAEs in 60 people.
Fatal SAEs: 29
Most common SAEs were pneumonia (n=27, 11.0%), cardiac arrest (n=5, 2.0%), respiratory failure (n=4, 1.6%) and recurrent stroke (n=3, 1.2%).
One SAE (0.4%) was considered possibly related to PES: pneumonia related to catheter insertion leading to sepsis.
There was no difference in the risk of individual SAEs between diagnostic groups.
System | SAE Term | All, n (%) | Time to event, days (SD) |
N | 245 | ||
Participants | |||
SAE | 60 (24.5) | 25 (44) | |
Fatal SAE | 29 (11.8) | 34 (33) | |
Events | |||
SAE | 74 | ||
Fatal SAE | 30 (40.5) | ||
Cardiac | Cardiac Atrial fibrillation | 2 (0.8) | 36 (45) |
Cardiac arrest | 5 (2.0) | 38 (43) | |
Cardiac failure | 1 (0.4) | 74 (0) | |
Gastrointestinal | Gastrointestinal Liver cancer | 1 (0.4) | 51 (0) |
Liver insufficiency | 1 (0.4) | 16 (0) | |
Parotitis | 1 (0.4) | -9 (0)* | |
Peritonitis | 1 (0.4) | 22 (0) | |
Neurological | Neurological Brain Abscess | 1 (0.4) | 4 (0) |
Encephalomyelitis | 1 (0.4) | 93 (0) | |
Hydrocephalus | 1 (0.4) | 64 (0) | |
PRES | 1 (0.4) | 41 (0) | |
Reduced consciousness | 1 (0.4) | 7 (0) | |
Seizures | 2 (0.8) | 103 (39) | |
Stroke | 3 (1.2) | 18 (30) | |
Other | Death, cause unknown | 2 (0.8) | 68 (97) |
Dehydration | 1 (0.4) | 66 (0) | |
Infection/sepsis, other | 3 (1.2) | 21 (11) | |
Multiple organ failure | 1 (0.4) | 60 (0) | |
Wound healing disorder | 1 (0.4) | 51 (0) | |
Renal | Renal Acute kidney injury | 1 (0.4) | 38 (0) |
Haematuria | 1 (0.4) | 78 (0) | |
Urosepsis | 2 (0.8) | 54 (44) | |
Respiratory | Respiratory Lung cancer | 1 (0.4) | 37 (0) |
Pneumonia/RTI | 26 (10.6) | 22 (35) | |
Pneumonia/RTI** | 1 (0.4) | 2 (0) | |
Respiratory failure | 4 (1.6) | 12 (33) | |
Severe bronchitis | 1 (0.4) | 30 (0) | |
Tracheal stenosis | 1 (0.4) | 34 (0) | |
Vascular | Fainting | 1 (0.4) | 87 (0) |
Peripheral vascular disease | 1 (0.4) | 15 (0) | |
Pulmonary embolism | 2 (0.8) | 16 (2) |
PRES: posterior reversible encephalopathy syndrome; RTI: respiratory tract infection/chest infection; SAE:
serious adverse event.
*Started after consent/before treatment
**1 case of chest sepsis "possibly-related" to catheter insertion.
Study 6 Restivo DA (2013)
Study details
Study type | Double-blinded (patient, assessor), sham-controlled pilot RCT |
Country | Italy |
Recruitment period | Not reported |
Study population and number | n=20 (10 active treatment) People with dysphagia related to MS |
Age and sex | Mean 39.7; 65% female |
Patient selection criteria | Inclusion criteria: Expanded Disability Status Scale (EDSS) score of 7.5 or less (scored out of 10, higher numbers indicate worse disability), subjects in a stable phase of the disease, without relapses or a worsening major than 1 point at the EDSS in the previous 3 months; swallowing difficulty for liquids, solids or both, present for at least 2 consecutive months. Exclusion criteria: neurologic disease other than MS, older than 60 (because nonspecific swallowing abnormalities may occur around and especially above the age of 60), concomitant illness or upper gastrointestinal disease, inability to give informed consent because of cognitive impairment. |
Technique | PES. bipolar platinum pharyngeal ring electrodes built into a 3 mm-diameter intraluminal catheter connected to a constant/current electrical simulator Electric current at 5 Hz was administered for 10 minutes each day for 5 days. A stimulation intensity of 75% maximum tolerated was used (calculated as the 75% of the current between sensory threshold and pain threshold). The mean treatment stimulation level was 14.2 mA. |
Follow up | 4 weeks |
Conflict of interest/source of funding | Conflict of interest: Not reported Source of funding: supported by a Grant FISM (Fondazione Italiana Sclerosi Multipla onlus) |
Analysis
Study design issues: This RCT was a pilot study to assess the efficacy and safety of PES for the treatment of dysphagia in people with MS. Patients were randomised 1:1 to PES or sham using a computer-generated list. In people assigned to sham, the same electrode was used, but no current was applied. Patients and outcome assessors were blinded to treatment allocation, treating researchers were unblinded. As patients could feel the effects of treatment, or the absence of treatment with sham, some patients may have become prematurely unblinded to treatment allocation.
The outcomes included:
Primary: PAS
Secondary: variation in the electromyographic (EMG) measures: 1) duration of laryngeal transductor excursion (A-0 interval). 2) duration of the EMG activity of suprahyoid/submental (SHEMG-D) muscles. 3) interval between onset of EMG activity of suprahyoid/submental muscles and the onset of the laryngeal elevation (AeC interval). 4) duration of the inhibition (pause) of the cricopharyngeal (CP) muscle (CPEMG-P). 5) cortical motor thresholds (MT) recorded from the left CP muscle after TMS of the contralateral pharyngeal motor area.
Various statistical tests were used to compare pre-post and between-group outcomes. Wilcoxon signed ranks tests and analysis of variance (ANOVA) were used to evaluate differences in outcomes between PES and sham arms. Post-hoc testing with Bonferroni correction for multiple comparisons was used. p<0.05 was considered statistically significant.
Study population issues: There were no significant differences in baseline outcome measures between the PES and sham groups. Baseline demographic data were not provided.
Key efficacy findings
Primary outcome
Number of people analysed: 20
In the PES group, there was a statistically significant decrease in PAS score from baseline to each post-stimulation period (p<0.001). A similar decrease was not observed in the sham group.
Outcome | PES | Sham | ||||||
Baseline | T1 | T2 | T3 | Baseline | T1 | T2 | T3 | |
PAS | 6.4 ± 0.9 | 3.1 ± 0.8 | 3.3 ± 1.0 | 4.4 ± 1.1 | 6.5 ± 0.8 | 6.2 ± 1.4 | 6.3 ± 1.0 | 6.4 ± 0.9 |
PAS, penetration-aspiration scale; PES, pharyngeal electrical stimulation; T1, immediately after final treatment session; T2, 2 weeks after final treatment session; T3, 4 weeks after final treatment session.
Secondary outcomes
Number of people analysed: 20
In the secondary outcomes, ANOVA showed a statistically significant main effect of groups (p<0.05 for A–0 interval, A–C interval, SHEMG-D; p<0.01 for CPEMG-P; p<0.05 for cortical MT), treatment (p<0.0001) and a statistically significant interaction between group and treatment (p<0.0001). This statistical significance was confirmed by post-hoc testing (p<0.0001).
Outcome | PES | Sham | ||||||
Baseline | T1 | T2 | T3 | Baseline | T1 | T2 | T3 | |
A–0 interval | 767.7 ± 181.4 | 595.6 ± 75.5 | 594.9 ± 67.7 | 631.8 ± 83.8 | 771.5 ± 181.0 | 768.2 ± 169.5 | 767.1 ± 179.0 | 770.4 ± 180.0 |
SHEMG-D | 1085.2 ± 151.4 | 922.4 ± 106.2 | 929.6 ± 106.8 | 952.5 ± 124.8 | 1076.3 ± 154.2 | 1073.3 ± 156.4 | 1075.2 ± 156.0 | 1078.2 ± 153.8 |
A–C interval | 579.0 ± 244.1 | 456.8 ± 164.6 | 315 ± 166.9 | 361.5 ± 216.5 | 584.6 ± 241.1 | 582.8 ± 241.7 | 584 ± 241.4 | 585.6 ± 241.3 |
CPEMG-P | 216.8 ± 113.5 | 456.8 ± 164.6 | 455.1 ± 158.3 | 387.4 ± 120.2 | 215.1 ± 112.7 | 216.6 ± 111.1 | 216.4 ± 111.2 | 216.8 ± 111.3 |
MT (%) | 55.7 ± 5.8 | 48.9 ± 4.5 | 48.8 ± 4.6 | 52 ± 5.0 | 55.4 ± 5.4 | 55.6 ± 4.5 | 55.7 ± 5.5 | 55.7 ± 5.5 |
Key safety findings
Safety findings were not reported.
Study 7 Herrmann C (2022)
Study details
Study type | Single centre, open-label, active comparator controlled pilot RCT |
Country | Germany |
Recruitment period | 2018 to 2020 |
Study population and number | n=20 (10 active treatment) People with dysphagia related to ALS. |
Age and sex | PES group: mean 76.0; 50% female |
Patient selection criteria | Inclusion criteria: Patients with possible, probable or definitive ALS with combined upper motor neurone/lower motor neurone bulbar involvement with moderate to severe dysphagia (as defined as a PAS value of at least 4 in thin liquid as assessed by fibreoptic endoscopic evaluation of swallowing at baseline). Exclusion criteria: atypical diagnoses (including primary lateral sclerosis, progressive muscular atrophy, and progressive bulbar palsy), tracheostomy, severe psychiatric disorders or dementia, implanted pacemaker or cardiac defibrillator and severe cardiopulmonary diseases. |
Technique | PES with Phagenyx (Phagenesis, Ltd, Manchester, UK) in addition to standard logopaedic therapy (SLT). Electric current at 5 Hz was administered for 10 minutes each day for 3 days. The current of the stimulation was calculated as the threshold current (the current at which the patient can first detect stimulation) plus 75% of the difference between threshold and tolerance current (the current at which the patient does not want the current increased further). The median treatment stimulation level was approximately 12.7 mA. SLT was given over 45 minutes each day for 3 days and involved restitutional procedures (for example, passive manual treatment, tactile and thermal stimulation and moderate movement exercises), compensatory procedures (for example, changes in posture or specific swallowing techniques), and adaptive procedures (for example, an adaption of patients' eating and drinking habits). |
Follow up | 3 months |
Conflict of interest/source of funding | Conflict of interest: The authors declared no potential conflicts of interest. Source of funding: Phagenesis, the manufacturer of a PES device, supplied the catheters and stimulation device for free. Data collection, analysis, interpretation and publication were performed by the research team without involvement of Phagenesis. |
Analysis
Follow up issues: In the PES group, 1 patient did not complete treatment after 1 day due to pneumonia and dislocation of the gastric tube. Over the entire duration of the study, there were 6 (60%) dropouts in the PES group compared with 1 (10%) dropouts in the control group. Dropouts in both groups were mainly caused by the patients' request to not perform subsequent study visits at the hospital due to further disease progression and severe disability. Two patients in the PES group died during the study due to disease progression.
Study design issues: This RCT was a pilot study to assess the efficacy and safety of PES for the treatment of dysphagia in people with ALS. The sample size was determined by practicality, not statistical power. People were randomised 1:1 to PES plus SLT or to SLT alone. Treatments were open label, with patients, treatment administrators, and assessors were unblinded to treatment assignment.
The outcomes included:
Primary: PAS
Secondary: Swallowing-specific QoL, DSRS, classification of leaking and residues (Residues are parts of the bolus that remain in the pharynx after swallowing and put the patient at risk of aspiration, while leaking describes that solid or fluid food enter the pharynx before triggering swallowing reflex), Clinical Evaluation of Swallowing (a description of this scale was not provided), and the ALSFRS-R.
All statistical tests were performed at a 2-sided level of alpha of 0.05 and interpreted as exploratory. An adjustment for multiple comparisons was not done.
Study population issues: Patients in the PES group were statistically significantly older than patients in the control group (76.0 versus 57.5 years). There were no other statistically significant differences between the groups.
Key efficacy findings
Primary outcome
Number of people analysed: 20
There were no statistically significant differences in PAS score improvement between the treatment groups at any of the follow up visits.
Outcome | Treatment group | Day 1 | Day 4 | Week 3 | Month 3 |
PAS | PES | −0.8 (−1.5 to −0.3) | −0.2 (−1.9 to 0.5) | −1.1 (−2.0 to 0.5) | −0.02 (−2.0 to 2.2) |
Control | −1.8 (−2.2 to −0.2) | −1.5 (−1.8 to −1.2) | −1.4 (−1.7 to 0.5) | −0.7 (−1.0 to 0.5) | |
p-value | 0.32 | 0.74 | 0.69 | 0.71 |
Data are median (IQR).
IQR, interquartile range; PAS, penetration-aspiration scale; PES, pharyngeal electrical stimulation.
Secondary outcomes
Number of people analysed: 20
There were no statistically significant differences in any of the secondary outcome measures between the treatment groups at any of the follow up visits.
Outcome | Treatment group | Day 1 | Day 4 | Week 3 | Month 3 |
ALSFRS-R | PES | Not analysed | 0.0 (−3.0 to 2.0) | −1.5 (−6.8 to 1.5) | −0.5 (−1.0 to 1.5) |
Control | 0.0 (−1.0 to 2.0) | −1.0 (−4.0 to 0.0) | −1.0 (−7.5 to 0.5) | ||
p-value | 0.37 | 0.99 | 0.54 | ||
SWAL-QOL | PES | 9.5 (−3.8 to 24.0) | 0.5 (−17.0 to 16.0) | −6.0 (−12.0 to 8.5) | 4.0 (4.0 to 9.0) |
Control | −2.0 (−11.0 to 13.0) | 3.0 (−17.0 to 21.0) | 0.0 (−17.0 to 11.0) | −4.0 (−36.0 to 3.3) | |
p-value | 0.29 | 0.52 | 0.93 | 0.07 | |
DSRS | PES | −1.0 (−2.0 to −0.3) | −1.0 (−1.0 to 0.0) | −0.5 (−2.0 to 0.3) | −2.0 (−2.0 to 1.0) |
Control | −1.0 (−1.0 to −1.0) | −1.0 (−2.0 to −1.0) | 0.0 (−1.0 to 0.0) | 0.0 (−1.0 to 0.5) | |
p-value | 0.90 | 0.09 | 0.79 | 0.46 | |
Leaking | PES | −0.2 (−0.32 to 0.06) | −0.1 (−0.18 to −0.03) | −0.09 (−0.31 to 0.09) | −0.05 (−0.4 to 0.21) |
Control | 0.0 (−0.16 to 0.21) | 0.06 (−0.19 to 0.42) | −0.21 (−0.25 to 0.14) | −0.02 (−0.45 to 0.16) | |
p-value | 0.08 | 0.12 | 0.73 | 0.95 | |
Residues | PES | 0.0 (−0.57 to 0.03) | −0.15 (−0.37 to 0.19) | −0.34 (−1.1 to 0.17) | 0.0 (−0.12 to 0.11) |
Control | −0.24 (−0.66 to 0.07) | −0.32 (−0.55 to −0.25) | −0.2 (−0.41 to 0.0) | −0.51 (−0.67 to 0.01) | |
p-value | 0.95 | 0.09 | 0.58 | 0.28 | |
CES | PES | 0.0 (−2.0 to 1.5) | 1.0 (−3.0 to 4.0) | 1.0 (−1.5 to 3.0) | 0.5 (−1.0 to 3.5) |
Control | −1.5 (−2.0 to 0.2) | 0.0 (−4.0 to 1.0) | −1.0 (−1.8 to 0.8) | 1.5 (0.0 to 4.0) | |
p-value | 0.73 | 0.10 | 0.19 | 0.57 |
Data are median (IQR).
ALSFRS-R, Amyotrophic Lateral Sclerosis Functional Rating Scale Revised; CES, Clinical Evaluation of Swallowing; DSRS, Dysphagia Severity Rating Scale; IQR, interquartile range; PAS, Penetration Aspiration Scale; PES, pharyngeal electrical stimulation; SWAL-QOL, Swallowing Quality of Life.
Key safety findings
Number of people analysed: 10
Two minor adverse events were observed:
Uncomfortable feeling in the pharynx while using non-invasive ventilation after PES, n=1
Mild burning pain in the nasopharynx after PES due to an erythema, n=1
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