Swallowing impairment (dysphagia) post-stroke results in poorer outcomes. Pharyngeal electrical stimulation (PES) is a potential treatment for post-stroke dysphagia. In a post hoc analysis, we investigated PES using videofluoroscopy swallow studies (VFSS) from the STEPS trial incorporating multiple measures of safety (penetration aspiration scale-PAS), speed and duration (timing), and efficiency (clearance), as opposed to the original trial which only measured PAS scores. 81 randomised participants (PES (
Dysphagia is associated with poorer outcomes [
Data from the STEPS trial was used to carry out the analysis [
Every swallow performed to clear each
The study underpinning the data had national ethics approvals and patients (or surrogates) had given written informed consent. The trial was registered as
Baseline characteristics and baseline VFSS measures of participants were determined using descriptive statistics. The Chi-Square test and Fisher’s Exact Probability Test (binary and ordinal variables) and Welch’s
Details of reliability information for the safety, timing, and clearance measures used in this study have been submitted for publication.
From the original dataset, 126 (of 162) participants received PES or sham and had both a VFSS completed at baseline and 2 weeks. This group comprised the primary outcome population in the STEPS study and was also used for the current study. Further analysis revealed that 42 participants in this group had VFSS data recorded at a frame rate <25 fps, two files were missing, and one file was unanalysable. These files were excluded from this study (the excluded group). This resulted in a final total of 81 files (64.3%) from the 126 participants in the timings and clearance analysis for this study (the included group). In this included group, 71 files (88%) were recorded at a frame rate of 25 fps and 10 files (12%) were recorded at 30 fps. Supplementary figure
Table
Baseline characteristics for participants in STEPS: excluded vs. included (
All | Excluded | Included | PES | Sham | ||||
---|---|---|---|---|---|---|---|---|
Patients | 126 | 45 | 81 | 81 | 43 | 38 | ||
Age, | 126 | 73.4 (11.4) | 73.3 (11.8) | 73.4 (11.2) | 0.98 | 81 | 72.8 (10.0) | 74.1 (12.5) |
Sex, female (%) | 126 | 49 (38.9) | 15 (33.3) | 34 (42.0) | 0.45 | 81 | 21 (48.8) | 13 (34.2) |
Ethnicity, white (%) | 126 | 108 (85.7) | 43 (95.6) | 65 (80.2) | 81 | 39 (90.7) | 36 (94.7) | |
Modified Rankin Scale (/6) | 126 | 4.1 (1.0) | 4.0 (1.1) | 4.1 (1.0) | 0.47 | 81 | 3.9 (1.0) | 4.4 (0.9) |
Barthel Index (/100) | 126 | 28.9 (29.8) | 31.4 (30.8) | 27.4 (29.4) | 0.48 | 81 | 33.8 (32.7) | 20.1 (23.4) |
Stroke | 3 (6.7) | 12 (14.8) | 0.25 | 81 | 43 | 37 | ||
Previous (%) | 126 | 15 (11.9) | 9 (20.9) | 3 (7.9) | ||||
Type, ischaemic (%) | 110 | 96 (87.3) | 32 (86.5) | 64 (87.7) | 1.00 | 73 | 33 (86.8) | 31 (88.6) |
Side of CT lesion (%) | 123 | 0.25 | 80 | 43 | 37 | |||
Left | 55 (44.7) | 20 (46.5) | 35 (43.8) | 19 (44.2) | 16 (43.2) | |||
Right | 50 (40.7) | 14 (32.6) | 36 (45.0) | 18 (41.9) | 18 (48.6) | |||
No lesion | 18 (14.6) | 9 (20.9) | 9 (11.3) | 6 (14.0) | 3 (8.1) | |||
Syndrome (%) | 126 | 0.31 | 81 | |||||
TACS | 35 (27.8) | 13 (28.9) | 22 (27.2) | 11 (25.6) | 11 (28.9) | |||
PACS | 49 (38.9) | 14 (31.1) | 35 (43.2) | 21 (48.8) | 14 (36.8) | |||
Lacunar | 41 (32.5) | 17 (37.8) | 24 (29.6) | 11 (25.6) | 13 (34.2) | |||
POCS | 1 (0.8) | 1 (2.2) | 0 (0) | 0 (0) | 0 (0) | |||
Severity, NIHSS (/42) | 126 | 10.1 (6.5) | 9.5 (7.3) | 10.4 (6.0) | 0.48 | 81 | 10.1 (6.1) | 10.8 (5.9) |
Dysphasia, NIHSS (%) | 126 | 44 (34.9) | 13 (28.9) | 31 (38.3) | 0.33 | 81 | 17 (39.5) | 14 (36.8) |
Onset to randomisation (days) mean (SD) | 126 | 16.2 (9.9) | 15.2 (8.3) | 16.8 (10.7) | 0.33 | 81 | 15.4 (10.3) | 18.4 (11.1) |
Median [IQR] | 14 [11] | 15.0 [12] | 14.0 [16] | 15.5 [15] | 13.0 [13] | |||
DSRS (/12) | 126 | 7.4 (3.7) | 7.8 (3.7) | 7.1 (3.7) | 0.35 | 81 | 7.4 (4.0) | 6.8 (3.2) |
TOR-BSST, failed (%) | 126 | 122 (96.8) | 45 (100) | 77 (95.1) | 0.30 | 81 | 41 (95.3) | 36 (94.7) |
Feeding route (%) | 126 | 0.14 | 81 | 43 | 38 | |||
Oral, normal diet | 7 (5.6) | 5 (11.1) | 2 (2.5) | 2 (4.7) | 0 (0) | |||
Oral, soft diet | 36 (28.6) | 9 (20.0) | 27 (33.3) | 13 (30.2) | 14 (36.8) | |||
Nasogastric | 70 (55.6) | 27 (60.0) | 43 (53.1) | 25 (58.1) | 18 (47.4) | |||
PEG | 2 (1.6) | 0 (0) | 2 (2.5) | 2 (4.7) | 0 (0) | |||
Other | 11 (8.7) | 4 (8.9) | 7 (8.6) | 1 (2.3) | 6 (15.8) | |||
Weight (kg) | 126 | 73.0 (16.1) | 74.1 (16.5) | 72.4 (15.9) | 0.58 | 81 | 71.5 (14.8) | 73.4 (17.2) |
Body mass index (kg/m2) | 122 | 25.6 (4.9) | 25.7 (4.9) | 25.5 (4.9) | 0.88 | 77 | 25.8 (4.3) | 25.3 (5.5) |
Mid-arm circumference (cm) | 125 | 28.5 (3.6) | 28.2 (3.4) | 28.6 (3.7) | 0.61 | 80 | 28.3 (3.4) | 28.9 (4.0) |
Albumin (g/L) | 120 | 3.6 (0.6) | 3.6 (0.6) | 3.7 (0.5) | 0.44 | 77 | 3.7 (0.6) | 3.6 (0.5) |
Chest infection (%) | 126 | 5 (4.0) | 3 (6.7) | 2 (2.5) | 0.35 | 81 | 1 (2.3) | 1 (2.6) |
CT: computed tomography; DSRS: dysphagia severity rating scale; ICH: intracerebral haemorrhage; NIHSS: National Institutes of Health Stroke Scale; PEG: percutaneous endoscopic gastrostomy; TACS: total anterior circulation syndrome; PACS: partial anterior circulating syndrome; POCS: posterior communicating syndrome; TOR-BSST: Toronto Bedside Swallowing Screening Test. PES group associated with lower mRS (
Fifteen hospital sites (supplementary figure
When comparing outcomes between the PES versus sham group, at baseline for the modal bolus (Table
VFSS measures at baseline for 5 ml mode swallow. Data are number (%) or mean (SD); comparison by Chi-Square (Exact) Test/Fisher’s Exact Test or Welch’s
5 ml measures-mode swallow | All | PES | Sham | |
---|---|---|---|---|
PAS, modal bolus | 72 | 4.4 (2.9) | 4.3 (3.1) [38] | 4.5 (2.6) [34] |
PAS, mean all boli | 72 | 4.5 (1.8) | 4.4 (1.9) [38] | 4.7 (1.7) [34] |
OTT (ms) | 40 | 2.14 (3.39) | 2.65 (4.14) [25] | 1.30 (1.16) [15] |
SRT | 62 | 2.07 (6.55) | 2.32 (8.53) [33] | 1.77 (3.20) [29] |
ILC | 56 | 2.55 (6.87) | 2.91 (9.08) [29] | 2.16 (3.29) [27] |
LVC_rt | 57 | 0.38 (0.15) | 0.39 (0.17) [29] | 0.38 (0.12) [28] |
LCD | 56 | 0.44 (0.21) | 0.50 (0.25) [28] | 0.39 (0.13) [28] |
PRT | 36 | 0.86 (0.12) | 0.89 (0.13) [20] | 0.82 (0.10) [16] |
PTT | 37 | 3.73 (8.36) | 4.29 (10.88) [20] | 3.06 (3.96) [17] |
UOSD | 38 | 0.62 (0.16) | 0.65 (0.17) [20] | 0.59 (0.13) [18] |
Initiation of pharyngeal swallow (0-4) | 69 | 37 | 32 | |
Bolus head-ramus | 10 (14.5) | 5 (13.5) | 5 (15.6) | |
Bolus head-valleculae | 12 (17.4) | 10 (27.0) | 2 (6.3) | |
Bolus head-laryngeal surface | 8 (11.6) | 2 (5.4) | 6 (18.8) | |
Bolus head-pyriforms | 39 (56.5) | 20 (54.1) | 19 (59.4) | |
No visible initiation | 0 (0) | 0 (0) | 0 (0) | |
Oral residue (0-4) | 56 | 28 | 28 | |
Complete clearance | 0 (0) | 0 (0) | 0 (0) | |
Trace residue | 12 (21.4) | 9 (32.1) | 3 (10.7) | |
Residue collection | 42 (75.0) | 18 (64.3) | 24 (85.7) | |
Majority bolus remaining | 1 (1.8) | 1 (3.6) | 0 (0) | |
Minimal/no clearance | 1 (1.8) | 0 (0) | 1 (3.6) | |
Pharyngeal residue (0-4) | 63 | 34 | 29 | |
Complete clearance | 4 (6.3) | 3 (8.8) | 1 (3.4) | |
Trace residue | 19 (30.2) | 11 (32.4) | 8 (27.6) | |
Residue collection | 39 (61.9) | 19 (55.9) | 20 (69.0) | |
Majority bolus remaining | 0 (0) | 0 (0) | 0 (0) | |
Minimal/no clearance | 1 (1.6) | 1 (2.9) | 0 (0) | |
No. of swallows to clear 5 ml | 72 | 1.1 (1.1) | 1.3 (1.1) [38] | 0.8 (1.0) [34] |
LCD was shorter in the sham group (
Comparison of PAS, timing, and clearance measures for 5 ml mode swallow, by change score from baseline to two weeks, using Independent Samples
5 ml measures–mode swallow | PES | No PES | Difference (95% CI) | |||
---|---|---|---|---|---|---|
PAS, modal bolus | 38 | -1.45 (3.06) | 33 | -0.85 (2.54) | -0.60 (-1.93, 0.73) | 0.37 |
PAS, mean all boli | 38 | -0.99 (1.66) | 34 | -0.95 (1.58) | -0.04 (-0.80, 0.72) | 0.91 |
OTT | 20 | -0.64 (1.83) | 9 | -0.51 (1.37) | -0.13 (-1.41, 1.14) | 0.83 |
SRT | 28 | -1.98 (8.94) | 27 | -1.05 (3.39) | -0.92 (-4.60, 2.76) | 0.62 |
ILC | 24 | -2.04 (9.73) | 24 | -1.17 (3.55) | -0.87 (-5.19, 3.45) | 0.68 |
LVC_rt | 25 | -0.07 (0.15) | 25 | -0.01 (0.19) | -0.07 (-0.17, 0.03) | 0.18 |
LCD | 22 | 0.04 (0.18)) | 25 | -0.00 (0.19) | 0.04 (-0.07, 0.15) | 0.43 |
PRT | 15 | 0.01 (0.16) | 9 | 0.01 (0.08) | -0.00 (-0.10, 0.10) | 0.97 |
PTT | 15 | -3.66 (12.12) | 10 | -1.49 (5.26) | -2.17 (-9.55, 5.21) | 0.55 |
UOSD | 15 | 0.03 (0.15) | 10 | 0.00 (0.09) | 0.03 (-0.07, 0.13) | 0.58 |
Initiation of pharyngeal swallow (0-4) | 36 | 0 [2] | 32 | 0 [1] | -0.5 (-1,0) | 0.52 |
Ramus | 8 (22.2) | 5 (15.6) | ||||
Valleculae | 6 (16.7) | 2 (6.3) | ||||
Laryngeal surface | 5 (13.9) | 3 (9.4) | ||||
Pyriforms | 17 (47.2) | 22 (68.8) | ||||
No visible initiation | 0 (0.0) | |||||
Oral residue (0-4) | 22 | 0 [0] | 23 | 0 [0] | -0.5 (-1,0) | 0.64 |
Complete clearance | 0 (0.0) | 0 (0.0) | ||||
Trace residue | 7 (31.8) | 5 (21.7) | ||||
Residue collection | 14 (63.6) | 18 (78.3) | ||||
Majority bolus remaining | 1 (4.5) | 0 (0.0) | ||||
Minimal/no clearance | 0 (0.0) | 0.(0.0) | ||||
Pharyngeal residue (0-4) | 31 | 0 [0] | 29 | 0 [1] | 0 (-1,0) | 0.53 |
Complete clearance | 2 (6.5) | 0 (0.0) | ||||
Trace residue | 11 (35.5) | 14 (48.3) | ||||
Residue collection | 18 (58.1) | 15 (51.7) | ||||
Majority bolus remaining | 0 (0.0) | 0.(0.0) | ||||
Minimal/no clearance | 0 (0.0) | 0 (0.0) | ||||
No. of swallows to clear 5 ml | 38 | 0.11 (1.39) | 33 | 0.12 (1.22) | -0.02 (-0.63, 0.60) | 0.96 |
VFSS measures at baseline for 50 ml bolus (comparison by Chi-square/Fisher’s Exact Test or Welch’s
50 ml measures at baseline | N | All | PES | Sham |
---|---|---|---|---|
PAS, 50 ml worst | 49 | 6.7 (1.8) | 6.6 (1.7) [25] | 6.8 (2.0) [24] |
PAS, 50 ml mean | 49 | 3.6 (1.9) | 3.3 (1.8) [25] | 3.9 (1.9) [24] |
No. swallows to clear | 49 | 7.8 (5.0) | 8.0 (5.5) [25] | 7.5 (4.6) [24] |
Initiation of pharyngeal swallow | 45 | 22 | 23 | |
Bolus head-ramus | 3 (6.7) | 3 (13.6) | 0 (0.0) | |
Bolus head-valleculae | 4 (8.9) | 2 (9.1) | 2 (8.7) | |
Bolus head-laryngeal surface | 5 (11.1) | 3 (13.6) | 2 (8.7) | |
Bolus head-pyriforms | 33 (73.3) | 14 (63.6) | 19 (82.6) | |
No visible initiation | 0 (0) | 0 (0.0) | 0 (0.0) | |
Oral residue (0-4) | 40 | 22 | 18 | |
Complete clearance | 0 (0) | 0 (0.0) | 0 (0.0) | |
Trace residue | 1 (2.5) | 1 (4.5) | 0 (0.0) | |
Residue collection | 37 (92.5) | 20 (90.9) | 17 (94.4) | |
Majority bolus remaining | 1 (2.5) | 1 (4.5) | 0 (0.0) | |
Minimal/no clearance | 1 (2.5) | 0 (0.0) | 1 (5.6) | |
Pharyngeal residue (0-4) | 43 | 23 | 20 | |
Complete clearance | 0 (0) | 0 (0.0) | 0 (0.0) | |
Trace residue | 10 (23.3) | 7 (30.4) | 3 (15.0) | |
Residue collection | 31 (72.1) | 14 (60.9) | 17 (85.0) | |
Majority bolus remaining | 1 (2.3) | 1 (4.3) | 0 (0.0) | |
Minimal/no clearance | 1 (2.3) | 1 (4.3) | 0 (0.0) |
Comparison of PAS, timing, and clearance measures for 50 ml worst swallow, by change score from baseline to two weeks, using Independent Samples
50 ml measures at 2 weeks | PES | No PES | Difference/95% (CI) | |||
---|---|---|---|---|---|---|
PAS, 50 ml worst | 24 | -1.04 (2.73) | 22 | -0.95 (3.03) | -0.09 (-1.81, 1.63) | 0.92 |
PAS, 50 ml mean | 24 | -0.42 (1.93) | 22 | -0.64 (1.59) | 0.22 (-0.83, 1.27) | 0.68 |
No. swallows to clear | 24 | -1.17 (4.30) | 22 | -1.27 (4.92) | 0.11 (-2.65, 2.87) | 0.94 |
Initiation of pharyngeal swallow (0-4) | 21 | 20 | 0.58 | |||
Bolus head-ramus | 4 (19.0) | 1 (5.0) | ||||
Bolus head-valleculae | 0 (0.0) | 0 (0.0) | ||||
Bolus head-laryngeal surface | 3 (14.3) | 5 (25.0) | ||||
Bolus head-pyriforms | 14 (66.7) | 14 (70.0) | ||||
No visible initiation | 0 (0.0) | 0 (0.0) | ||||
Oral residue (0-4) | 19 | 15 | 0.26 | |||
Complete clearance | 0 (0.0) | 0 (0.0) | ||||
Trace residue | 0 (0.0) | 2 (13.3) | ||||
Residue collection | 18 (94.7) | 13 (86.7) | ||||
Majority bolus remaining | 0 (0.0) | 0 (0.0) | ||||
Minimal/no clearance | 1 (5.3) | 0 (0.0) | ||||
Pharyngeal residue (0-4) | 21 | 17 | 0.35 | |||
Complete clearance | 0 (0.0) | 0 (0.0) | ||||
Trace residue | 7 (33.3) | 2 (11.8) | ||||
Residue collection | 14 (66.7) | 15 (88.2) | ||||
Majority bolus remaining | 0 (0.0) | 0 (0.0) | ||||
Minimal/no clearance | 0 (0.0) | 0 (0.0) |
When comparing outcomes of both groups (supplementary figure
There were no significant changes for IPS or any clearance measures; (supplementary figure
This current study only included imaging data from the original STEPS trial at ≥25 fps. Our findings with regards to PA scores agree with the overall conclusion from the original STEPS study which also did not show a significant change between groups for safety. Furthermore, this current study which conducted additional temporal and clearance measures on this data has not demonstrated any new or “undetected” significant differences between the groups. In other acute stroke treatment studies using PES, improvements in safety (PAS scores) were seen in smaller studies [
The significant improvement in PAS scores observed in both groups at two weeks could have been due to spontaneous recovery. Longitudinal observational studies at 1-month post-onset [
We chose the mode bolus as the primary method of analysis as it represents the most frequently occurring swallow pattern across a series of swallows. It therefore may be a more instructive way to measure PAS scores, being more representative of a patient’s unique swallow pattern, as opposed to the mean or median [
As with PAS scores, in the acute phase of stroke, one would expect a trend for longitudinal improvements in timings as patients recover [
No significant results were seen between the groups for the worst 50 ml bolus. Few studies have reported on swallowing larger boli (≥50 ml) in acute stroke patients, perhaps due to concerns regarding safety and one study that did evaluate swallowing of 100 ml of thin barium only included milder patients [
The numerous measures performed in this research represent a comprehensive analysis of swallow safety, timings, and clearance. The findings from this study suggest that including timings and clearance measures did not result in the detection of differences in swallow function that may have been missed using the PAS scale alone. Equally, in the numbers studied, it is probable that there was no effect to be detected, and hence, it is premature to conclude that only using the PAS is enough to capture change in swallowing function following an intervention. The main reason for lower numbers was due to reduced imaging quality and suboptimal frame rate in the final analysis. This has highlighted the importance of acquiring images at the correct frame rate and optimising data quality and field of view as much as possible.
This study has several strengths. These include analysis of a large dataset with deep phenotypic information from a high-fidelity phase III trial that followed a published protocol; a comprehensive analysis which encompasses all aspects of the swallow (safety, speed, duration, and efficiency) and is, to our knowledge, the first study to publish results of stroke patients focusing on the PAS scores from the mode swallow.
However, some limitations are present. As this real-life study included VFSS from 18 different hospitals in 5 countries inevitably, some images were of suboptimal quality, resulting in missing data as image quality was not good enough to allow measurements or were out of field of view. VFSS frame rates also varied both within and between sites which also reduced the number of files available for analysis. In addition, one site contributed significantly more data than other sites which may represent a bias within the results.
In summary, including measures of timing and clearance (in addition to safety measures) did not detect any further changes in swallowing function. Adequately powered studies, assessing the effect of PES in the acute stroke where PES is given solely to the PES group and at the optimal dose (preventing “undertreatment”), are required.
Data is not available for sharing due to commercial sensitivity.
P Bath is a consultant to Phagenesis; he is a professor of the Stroke Association Professor of Stroke Medicine and is a NIHR Senior Investigator. S Hamdy is a professor of neurogastroenterology, board director and CSO of Phagenesis, and hold stocks/shares in the company. E Michou, L Everton, and J Benfield have nothing to disclose.
The STEPS trial was sponsored and funded by Phagenesis Ltd. Partial data from this study was presented as a poster presentation in 2019 by Everton LF, Michou E, Benfield JK, Hamdy S, and Bath PM. Title: Effects of pharyngeal electrical stimulation on swallow timings, clearance, and safety: adhoc analysis from the Swallowing Treatment using Electrical Pharyngeal Stimulation (STEPS) Trial. International Journal of Stroke, 14 (4S), 2019. This research was funded by the National Institute for Health Research (NIHR) Senior Investigator’s Award (RC23B7). The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care.
Supplementary Table 1: summary of measures carried out on mode 5 ml bolus and worst 50 ml bolus. Supplementary Table 2: operational definitions of timing measures. Supplementary Figure 1: distribution of frame rates (