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    Interventional procedure overview of pharyngeal electrical stimulation for neurogenic dysphagia

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    Study 5 Suntrup S (2015)

    Study details

    Study type

    Single centre crossover RCT

    Country

    Germany

    Recruitment period

    June 2013 to August 2014

    Study population and number

    N=30 (20 active treatment)

    People with severe dysphagia and tracheostomy after stroke

    Age and sex

    PES group mean age= 63 (SD=15); 55% female (11/20)

    Sham group mean age= 67 (SD=15); 40% female (4/10)

    Patient selection criteria

    People who were tracheostomised after stroke and suffered from severe persistent dysphagia according to a standardised endoscopic swallowing evaluation for tracheostomy.

    Technique

    PES with Phagenyx (Phagenesis, Ltd, 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).

    Follow up

    Until discharge from hospital.

    Conflict of interest/ source of funding

    R. Dziewas was a member of the clinical advisory board of Phagenesis Ltd. The other authors declared they have no conflict of interest

    Analysis

    Follow up issues: all participants completed follow up.

    Study design issues: This single centre RCT assessed the efficacy and safety of PES to treat post-stroke dysphagia with tracheostomy. People with recent stroke and confirmed severe dysphagia were randomised 2:1 to PES or sham. Based on an assumed effect size of decannulation at 40%, 26 people would have been required to demonstrate statistical power. This was exceeded. A standardised protocol was followed to determine the primary outcome. This was a crossover study so people were unblinded after 24-72 hours meaning some comparative analyses of secondary outcomes (including length of stay) could not be meaningfully interpreted.

    Outcomes included:

    • Primary: Decannulation after 3 days of PES

    • Secondary: FOIS, mRS, length of stay in ICU, length of stay in hospital

    Study population issues: there were mostly no differences between groups on a range of demographic and clinical characteristics at baseline. The authors reported time to treatment was longer in the PES group and that this group showed more severe neurological impairment.

    Key efficacy findings

    Primary outcome: decannulation

    There was a statistically significantly higher likelihood of decannulation within 72 hours of treatment completion in the PES group (75% [15/20]) compared with sham (20% [2/10]; p<0.01). This was also a crossover trial and 71% (5/8) of patients in sham group that had severe persistent dysphagia and went on to receive PES were ready for decannulation 72 hours after treatment.

    Secondary outcomes

    Length of stay

    Mean overall length of stay was 1,028 hours (SD=409) in the PES arm and 1,017 hours (SD=493) in the sham arm (p=0.95). Mean Length of stay in ICU was 917 hours (SD=357) in the PES arm and 931 hours (SD=472) in the sham arm (p=0.92). Time from study treatment to discharge was 390 hours (SD=293) in the PES arm and 450 (SD=154) in the sham arm (p=0.55).

    FOIS at discharge

    PES (n=20)

    Sham (n=10)

    p-value

    Tube-dependent (1–3), n (%)

    8 (40%)

    6 (60%)

    0.30

    Total oral intake (4–7), n (%)

    12 (60%)

    4 (40%)

    mRS at discharge

    mRS score

    PES (n=20)

    Sham (n=10)

    p-value

    3, n (%)

    4 (20%)

    1 (10%)

    0.79

    4, n (%)

    9 (45%)

    5 (50%)

    5, n (%)

    7 (35%)

    4 (40%)

    Key safety findings

    No adverse events related to the procedure or device were recorded during the study. Overall rates of adverse events were not reported.

    Study 6 Bath PM (2020)

    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 tracheostomy; (C) mechanical ventilation in non-stroke, non-TBI; (D) TBI with or without the need for mechanical ventilation and tracheostomy; and (E) any other neurological cause not needing mechanical ventilation and tracheostomy.

    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 tracheostomy (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 below.

    • 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.

    DSRS outcomes

    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 below.

    • 66% (66/99) of people with tracheostomy could be decannulated after receiving PES. The magnitude of improvement at three months was greater (7.5 vs 2.1 points on the DSRS) in the decannulated compared to non-decannulated group.

    • 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.

    Secondary outcomes

    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.

    Summary of SAEs

    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 7 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 8 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-spiration 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