NATIONAL INSTITUTE FOR HEALTH AND CARE EXCELLENCE

NATIONAL INSTITUTE FOR HEALTH AND CARE EXCELLENCE INTERVENTIONAL PROCEDURES PROGRAMME Interventional procedure overview of transcutaneous neuromuscular electrical stimulation for oropharyngeal dysphagia Difficulty swallowing (dysphagia) can occur as a result of conditions such as stroke, multiple sclerosis, Parkinson s disease or traumatic brain injuries. Neuromuscular electrical stimulation aims to strengthen the muscles involved in swallowing by electrically stimulating nerves in the throat or neck through electrodes on the skin, to induce muscle contractions, while the patient practises swallowing exercises. Introduction The National Institute for Health and Care Excellence (NICE) has prepared this interventional procedure (IP) overview to help members of the Interventional Procedures Advisory Committee (IPAC) make recommendations about the safety and efficacy of an interventional procedure. It is based on a rapid review of the medical literature and specialist opinion. It should not be regarded as a definitive assessment of the procedure. Date prepared This overview was prepared in August 2013 and updated in December 2013. Procedure name Transcutaneous neuromuscular electrical stimulation for oropharyngeal dysphagia IP overview: Transcutaneous neuromuscular electrical stimulation for oropharyngeal dysphagia 1 of 47

Specialist societies Royal College of Speech and Language Therapists Association of British Neurologists British Society of Gastroenterology British Association of Otorhinolaryngologists, Head and Neck Surgeons (ENT UK) British Society of Rehabilitation Medicine. Description Indications and current treatment Difficulty in swallowing (dysphagia) can result from neurological impairment affecting the muscles of the oropharynx. It can occur as a result of stroke, traumatic brain injury, disorders of cerebral development, neurodegenerative conditions and major head and neck surgery such as removing cancer. Dysphagia may lead to malnutrition, dehydration or aspiration pneumonia. This guidance only applies to adults with oropharyngeal dysphagia. Treatment options depend on the cause and severity of the dysphagia. Conservative treatments (traditional therapy) involve swallowing therapy to help the patient relearn swallowing techniques and strengthen oropharyngeal muscles. In severe cases nasogastric tubes or percutaneous endoscopic gastrostomy tubes may be used to provide nutritional support. What the procedure involves Transcutaneous neuromuscular electrical stimulation (NMES) is usually used as an adjunct to traditional swallowing therapy for treating oropharyngeal dysphagia. Swallowing therapy uses exercises to improve muscle function. The aim of NMES is to increase the effectiveness of swallowing therapy. Its mechanism of action is thought to include accelerating the development of muscle strength and promoting central or cortical recovery NMES is usually administered by a speech and language therapist after appropriate diagnosis and patient selection. Therapists need appropriate IP overview: Transcutaneous neuromuscular electrical stimulation for oropharyngeal dysphagia 2 of 47

training to use the procedure. The speech and language therapist places electrodes in selected positions on the patient s neck, through which small electrical currents are then passed to stimulate the peripheral nerve supply of the pharyngeal and/or laryngeal muscles. Stimulus intensity may be at a low sensory level, or at a higher motor level to trigger muscle contractions. Under the supervision of the therapist, the patient exercises their swallowing muscles while receiving electrical stimulation. Treatment duration recommendations vary by device but can be up to 1 hour. The mild electrical stimulation can produce feelings ranging from tingling and warmth to a grabbing sensation. The position of the electrodes and levels of current used vary from patient to patient. There is a range of NMES devices that use different electrode designs, positions and stimulus intensities. At an initial assessment, videofluoroscopy or clinical observation may be used to optimise the placement of treatment electrodes and to determine an appropriate stimulus intensity. Outcome measures Swallowing-related Quality of Life scale The Swallowing-related Quality of Life (SWAL-QOL) scale is designed to objectively measure a patient s perspective of the impact of dysphagia on their quality of life. The instrument has been validated and has favourable psychometric properties, including high internal consistency, reliability and reproducibility. It consists of 44 questions that evaluate 11 domains: swallowing as a burden, desire to eat, eating duration, frequency of symptoms, food selection, communication, fear of eating, mental health, social function, sleep and fatigue. SWAL-QOL domains are scored from 0 to 100 with higher scores indicating better quality of life. Swallow Function Scoring System The Swallow Function Scoring System (SFSS) is an assessment tool that measures the severity of dysphagia by identifying the consistency of liquid a patient can swallow without aspiration. The outcome measure consists of an ordinal scale ranging from 0 to 6. A score of 0 indicates severe dysphagia IP overview: Transcutaneous neuromuscular electrical stimulation for oropharyngeal dysphagia 3 of 47

where no solid or liquid is safe to swallow. A score of 6 indicates no swallowing deficit so that all liquids are tolerated. Functional Oral Intake Scale The Functional Oral Intake Scale (FOIS) is a 7-point ordinal scale that is used to describe the amount and types of food or liquid that patients can safely ingest on a consistent basis. The scale has been shown to have strong validity and reliability specific to patients with dysphagia caused by strokes. FOIS levels: 1. No oral intake. 2. Tube dependent with minimal or inconsistent oral intake. 3. Tube supplements with consistent oral intake. 4. Total oral intake of a single consistency. 5. Total oral intake of multiple consistencies needing special preparation. 6. Total oral intake with no special preparation, but must avoid specific foods or liquid items. 7. Total oral intake with no feeding restrictions. MD Anderson Dysphagia Inventory The MD Anderson Dysphagia Inventory (MDADI) is an assessment tool that was originally designed to assess the impact of dysphagia on the quality of life of patients with head and neck cancer. It consists of 20 questions that include a global assessment and 3 subscales: emotional, functional and physical. Each question is scored from 1 to 5 resulting in a minimum total score of 20 and a maximum of 100; higher scores indicate better quality of life. IP overview: Transcutaneous neuromuscular electrical stimulation for oropharyngeal dysphagia 4 of 47

Literature review Rapid review of literature The medical literature was searched to identify studies and reviews relevant to transcutaneous neuromuscular electrical stimulation for oropharyngeal dysphagia. Searches were conducted of the following databases, covering the period from their commencement to 22 August 2013: MEDLINE, PREMEDLINE, EMBASE, Cochrane Library and other databases. Trial registries and the Internet were also searched. No language restriction was applied to the searches (see appendix C for details of search strategy). Relevant published studies identified during consultation or resolution that are published after this date may also be considered for inclusion. The following selection criteria (table 1) were applied to the abstracts identified by the literature search. Where selection criteria could not be determined from the abstracts the full paper was retrieved. Table 1 Inclusion criteria for identification of relevant studies Characteristic Publication type Patient Intervention/test Outcome Language Criteria Clinical studies were included. Emphasis was placed on identifying good quality studies. Abstracts were excluded where no clinical outcomes were reported, or where the paper was a review, editorial, or a laboratory or animal study. Conference abstracts were also excluded because of the difficulty of appraising study methodology, unless they reported specific adverse events that were not available in the published literature. Patients with dysphagia. Neuromuscular electrical stimulation. Articles were retrieved if the abstract contained information relevant to the safety and/or efficacy. Non-English-language articles were excluded unless they were thought to add substantively to the English-language evidence base. IP overview: Transcutaneous neuromuscular electrical stimulation for oropharyngeal dysphagia 5 of 47

List of studies included in the IP overview This overview is based on 784 patients from 1 systematic review, 5 randomised controlled trials, 2 non-randomised comparative studies, 1 case series and 1 conference abstract. Other studies that were considered to be relevant to the procedure but were not included in the main extraction table (table 2) have been listed in appendix A. IP overview: Transcutaneous neuromuscular electrical stimulation for oropharyngeal dysphagia 6 of 47

Table 2 Summary of key efficacy and safety findings on transcutaneous neuromuscular electrical stimulation for oropharyngeal dysphagia Abbreviations used: ASHA-NOMS, American speech-language-hearing association national outcome measurement system; CDS, clinical dysphagia scale; DOSS, dysphagia outcome and severity scale; FDS, functional dysphagia scale; FOIS, functional assessment of oral intake; MASA, Mann assessment of swallowing ability; MDADI, MD Anderson dysphagia inventory; NMES, neuromuscular electrical stimulation; PAS, penetration and aspiration scale; PRT, progressive resistance training; SD, standard deviation; SFSS, swallowing function scoring system; SSA, standardised swallowing assessment; SWAL-QOL, swallowingrelated quality of life; TT, traditional therapy; TTS, thermal-tactile stimulation; VAS, visual analogue scale; VFSS, videofluoroscopic swallowing study Study details Key efficacy findings Key safety findings Comments Tan (2013) 1 Systematic Review and Meta-analysis China Literature searches: 1966 to December 2011 Study population: patients with dysphagia due to various aetiologies n=7 studies: 291 patients (175 NMES vs 116 TT) Age: reported for individual studies but not pooled together Sex: 66% male Study/patient selection criteria: clinical trials, including randomised controlled and quasiexperimental trials, comparing NMES with TT for treatment of adults with dysphagia of any Number of patients analysed: 291 (175 NMES vs 116 TT) Meta-analysis of standardised mean differences in swallowing function score change (multiple outcome measures used across studies) Group n (NMES vs TT) Standardised mean difference (95% CI) a P-value Overall effect b 175 vs 116 0.77 (0.13 1.41) 0.02 Overall effect after 112 vs 80 0.50 (0.20 0.80) 0.001 sensitivity analysis c Stroke b 103 vs 72 0.78 (-0.22 1.78) 0.13 Non-stroke 72 vs 44 0.63 (0.24 1.02) 0.002 a Standardised mean difference was obtained by pooling the changes from mean baseline FOIS, SFSS, ASHA-NOMS and MDADI scores of included studies. Standardised mean differences above 0 favour NMES, standardised mean differences below 0 favour TT. b I-squared test for heterogeneity indicated a high degree of heterogeneity between studies in the pooled comparison. c Sensitivity analysis excluded a study that reported outcomes superior to the other included studies. None of the included studies reported any adverse events associated with NMES. Follow-up issues: Heterogeneity in the number of NMES sessions that patients received (10 to 20 sessions). Study design issues: Two reviewers were involved in data extraction and quality assessments. Some included studies compared NMES-alone with TT-alone, while others compared NMES in combination with TT against TTalone. Study population issues: Heterogeneity in study populations: included patients with dysphagia of any aetiology. Other issues: High I-squared test for heterogeneity results (>83%) may affect the relevance of the pooled comparisons. There are some IP overview: Transcutaneous neuromuscular electrical stimulation for oropharyngeal dysphagia 7 of 47

Abbreviations used: ASHA-NOMS, American speech-language-hearing association national outcome measurement system; CDS, clinical dysphagia scale; DOSS, dysphagia outcome and severity scale; FDS, functional dysphagia scale; FOIS, functional assessment of oral intake; MASA, Mann assessment of swallowing ability; MDADI, MD Anderson dysphagia inventory; NMES, neuromuscular electrical stimulation; PAS, penetration and aspiration scale; PRT, progressive resistance training; SD, standard deviation; SFSS, swallowing function scoring system; SSA, standardised swallowing assessment; SWAL-QOL, swallowingrelated quality of life; TT, traditional therapy; TTS, thermal-tactile stimulation; VAS, visual analogue scale; VFSS, videofluoroscopic swallowing study Study details Key efficacy findings Key safety findings Comments Xia (2011) 2 Randomised controlled trial China Recruitment period: 2007 2010 Study population: patients with post-stroke dysphagia. n=120 (40 NMES-alone vs 40 NMES+TT vs TTalone) Age: mean 66 years Sex: 63% male Patient selection criteria: patients 40 80 years with confirmed cerebral infarction or cerebral haemorrhage, swallowing disorder confirmed by water drinking test, no pulmonary disease. Exclusion criteria: not reported Technique: NMES was delivered with an Number of patients analysed: 120 (40 NMES-alone vs 40 NMES+TT vs 40 TT-alone) Changes in outcome measures DOSS scores (higher scores indicate decreasing dysphagia severity) Before treatment (Mean±SD) a After treatment (Mean±SD) P value NMES-alone c 2.7±1.6 5.6±1.6 <0.01 NMES+TT b 2.5±1.6 6.9±1.6 <0.01 TT-alone c 2.7±1.6 5.3±1.4 <0.01 SSA scores (lower scores indicate better outcomes) Before treatment (Mean±SD) a After treatment (Mean±SD) P value NMES-alone c 38.7±6.9 29.6±4.2 <0.01 NMES+ TT b 39.5±7.1 21.4±3.5 <0.01 TT-alone c 40.9±6.4 20.1±3.8 <0.01 a No significant differences in baseline SWAL-QOL, DOSS and SSA scores were observed between study arms (p values>0.05). b NMES+TT group exhibited significantly greater improvements in scores compared with the NMES-alone and TT-alone groups at 4-week follow-up (p values<0.01). c No significant differences in scores were observed between NMES-alone and TT-alone groups at 4-week follow-up (p values>0.05). SWAL-QOL Scores Authors reported (in the text) significant improvements in SWAL-QOL scores in all groups (p values<0.01), with the NMES+TT group exhibiting significantly greater improvements compared with the other groups (p=0.01). The numerical reporting of these improvements was not in No adverse events were reported; however, it is unclear if they were actively monitored. NB: not included in the Tan 1 systematic review. Follow-up issues: No loss to follow-up reported. Study design issues: Method of randomisation not reported. All patients were assessed and treated 48 hours after presence of stable vital signs and absence of neurological signs. Outcome measures are poorly defined: additional information on scales was sought from cited papers. DOSS is a 7-point scale that measures dysphagia severity: 1 indicates no oral intake, 7 indicates no swallowing deficit. SSA is the stepwise implementation of the water swallowing test: lower scores indicate better outcomes. Study population issues: IP overview: Transcutaneous neuromuscular electrical stimulation for oropharyngeal dysphagia 9 of 47

Abbreviations used: ASHA-NOMS, American speech-language-hearing association national outcome measurement system; CDS, clinical dysphagia scale; DOSS, dysphagia outcome and severity scale; FDS, functional dysphagia scale; FOIS, functional assessment of oral intake; MASA, Mann assessment of swallowing ability; MDADI, MD Anderson dysphagia inventory; NMES, neuromuscular electrical stimulation; PAS, penetration and aspiration scale; PRT, progressive resistance training; SD, standard deviation; SFSS, swallowing function scoring system; SSA, standardised swallowing assessment; SWAL-QOL, swallowingrelated quality of life; TT, traditional therapy; TTS, thermal-tactile stimulation; VAS, visual analogue scale; VFSS, videofluoroscopic swallowing study Study details Key efficacy findings Key safety findings Comments Lim (2009) 3 Randomised controlled trial Korea Recruitment period: 2005 2006 Study population: patients with post-stroke dysphagia. n=36 (NMES+TTS vs TTS). Numbers randomised not reported Mean age: NMES+TTS group: 67.8 years, TTS group: 60.8 years Sex: 86% male Patient selection criteria: patients with a primary diagnosis of stroke, dysphagia confirmed by videofluoroscopy and a Mini-mental State Examination score 2. Exclusion criteria: patients unable to receive treatment for 1 hour, Number of patients analysed: 28 (16 NMES+TTS vs 12 TTS-alone) SFSS scores (higher scores indicate decreasing dysphagia severity) Initial score (median) Final score (median) P value NMES+TTS 2 4 <0.05 TTS-alone 3 4 <0.05 Statistically significant differences were observed in the changes in SFSS scores within groups as well as between groups at 4-week follow-up (p<0.05) PAS scores (lower scores indicate decreasing dysphagia severity) Group Bolus type Initial score (median) Final score (median) P value a NMES+TTS Semi-solid 5.5 2.5 <0.05 Liquid 7 5 <0.05 TTS-alone Semi-solid 3.5 4 NS Liquid 7 6.5 NS NS= not significant (p.0.05) a PAS scores improved significantly in the NMES+TTS group (p<0.05) but not in the TTS group. b NMES+TTS group exhibited significantly greater improvements in PAS scores compared with the TTS group (p<0.05). Progression to oral feeding 50% (6/12) NMES+TTS patients progressed to oral feeding 14% (1/7) TTS patients progressed to oral feeding Discomfort and satisfaction scores (higher scores indicate better outcomes) No adverse events were observed. NB: included in the Tan 1 systematic review. Follow-up issues: 22% of patients did not complete the study. Main reason was early transfer to another hospital. Study design issues: Patients randomised according to the order of enrolment. Single-blinded study: outcome assessor was blinded to group allocations. SFSS is a validated 7- point scale assessing the severity of swallowing function: 1 indicates severe dysphagia, 7 indicates no swallowing deficit. PAS score is an 8-point scale used to describe penetration or aspiration events: 1 indicates no penetration or aspiration, 8 indicates severe aspiration with no cough reflex. Discomfort score assessed using a scale IP overview: Transcutaneous neuromuscular electrical stimulation for oropharyngeal dysphagia 11 of 47

Abbreviations used: ASHA-NOMS, American speech-language-hearing association national outcome measurement system; CDS, clinical dysphagia scale; DOSS, dysphagia outcome and severity scale; FDS, functional dysphagia scale; FOIS, functional assessment of oral intake; MASA, Mann assessment of swallowing ability; MDADI, MD Anderson dysphagia inventory; NMES, neuromuscular electrical stimulation; PAS, penetration and aspiration scale; PRT, progressive resistance training; SD, standard deviation; SFSS, swallowing function scoring system; SSA, standardised swallowing assessment; SWAL-QOL, swallowingrelated quality of life; TT, traditional therapy; TTS, thermal-tactile stimulation; VAS, visual analogue scale; VFSS, videofluoroscopic swallowing study Study details Key efficacy findings Key safety findings Comments Ryu (2009) 4 Randomised controlled trial Korea Recruitment period: 2006 2007 Study population: patients with dysphagia following treatment for head and neck cancers. n=46 (21 NMES vs 25 sham stimulation) Mean age: NMES group: 63.4, sham stimulation: 60.8 Gender: 96% male Patient selection criteria: Patients>20 years who had dysphagia following the treatment of head and neck cancers with surgery or radiotherapy, were on a restricted diet and stable vital signs. Exclusion criteria: Number of patients analysed: 26 (14 NMES vs 12 Sham) FDS scores (lower scores indicate a better ability to eat ) Group Baseline (mean±sd) Follow-up (mean±sd) Change (mean±sd) NMES 33.9±13.2 22.4±13.4 11.4±8.1 Sham 38.6±15.9 35.3±17.7 3.3±14.0 P value 0.04 CDS scores (lower scores indicate better outcomes) Group Baseline (mean±sd) Follow-up (mean±sd) Change (mean±sd) NMES 46.1±21.0 44.8±19.6 1.4±2.9 Sham 42.8±16.5 44.3±17.7-1.5±5.0 P value 0.07 ASHA NOMS scores (higher scores indicate decreasing dysphagia severity) Group Baseline (mean±sd) Follow-up (mean±sd) Change (mean±sd) NMES 2.6±1.7 3.9±1.8 1.3±1.2 Sham 2.9±1.9 3.7±2.1 0.8±1.1 P value 0.27 MDADI scores (higher scores indicate a better quality of life) Group Baseline (mean±sd) Follow-up (mean±sd) Change (mean±sd) NMES 48.2±9.8 53.4±11.0 5.2±3.7 Sham 53.1±10.2 55.9±11.2 2.5±7.5 No adverse events were reported; however, it is unclear if they were actively monitored. NB: included in the Tan 1 systematic review. Follow-up issues: 33% (7/21) and 52% (13/25) lost to followup. Reasons included early discharge (10), unwillingness to participate (7), incorrect pathology diagnosed as inflammation (1), orocervical fistula (1 in NMES group), neck infection (1 in sham group). Study design issues: Method of randomisation not described. Double-blinded study: both patients and assessors were blinded to group allocations. FDS categorises 8 parameters of oral feeding: lip sealing, chewing and mastication, tongue protrusion, laryngeal elevation, reflex coughing, lesion location, tracheostomy and history of aspiration. Scores range from 0 to 100 IP overview: Transcutaneous neuromuscular electrical stimulation for oropharyngeal dysphagia 13 of 47

Abbreviations used: ASHA-NOMS, American speech-language-hearing association national outcome measurement system; CDS, clinical dysphagia scale; DOSS, dysphagia outcome and severity scale; FDS, functional dysphagia scale; FOIS, functional assessment of oral intake; MASA, Mann assessment of swallowing ability; MDADI, MD Anderson dysphagia inventory; NMES, neuromuscular electrical stimulation; PAS, penetration and aspiration scale; PRT, progressive resistance training; SD, standard deviation; SFSS, swallowing function scoring system; SSA, standardised swallowing assessment; SWAL-QOL, swallowingrelated quality of life; TT, traditional therapy; TTS, thermal-tactile stimulation; VAS, visual analogue scale; VFSS, videofluoroscopic swallowing study Study details Key efficacy findings Key safety findings Comments Permisirivanich (2009) 5 Randomised controlled trial Thailand Recruitment period: 2007 2008 Study population: patients with dysphagia following a stroke. n=28 (15 NMES vs 13 TT) Mean age: NMES group: 64.5, TT group: 64.7 Sex: 39.1% male Patient selection criteria: patients with VFSSconfirmed pharyngeal dysphagia with safe swallowing to random. Exclusion criteria: not specified Technique: NMES was delivered with an electrical current that had Number of patients analysed: 23 (12 NMES vs 11 TT) FOIS scores (higher scores indicate a better oral intake) Group Baseline score Follow-up score Mean change NMES 2.2±1.1 5.4±1.1 3.2±1.3 TT 2.4±1.2 4.8±1.5 2.5±1.0 P value 0.81 0.28 <0.001 91.7% of patients in the NMES group increased their FOIS oral intake score by at least one unit, while 90.9% of patients in the TT group increased their FOIS score by at least one unit (no p value reported). Adverse events were actively monitored; however, none were reported. NB: included in the Tan 1 systematic review. Follow-up issues: 3 patients in the NMES group and 2 patients in the TT group were lost to follow-up. Study design issues: Patients were randomised using a random numbers table. Authors describe the study as a singleblinded study; it is implied that assessors were blinded. Treatment was provided by one trained physiatrist. FOIS is a 7-item scale that assesses oral intake with 0 indicating no oral intake and 7 indicating oral intake with no feeding restrictions. Study population issues: Small sample sizes may affect significance test levels. IP overview: Transcutaneous neuromuscular electrical stimulation for oropharyngeal dysphagia 15 of 47

Abbreviations used: ASHA-NOMS, American speech-language-hearing association national outcome measurement system; CDS, clinical dysphagia scale; DOSS, dysphagia outcome and severity scale; FDS, functional dysphagia scale; FOIS, functional assessment of oral intake; MASA, Mann assessment of swallowing ability; MDADI, MD Anderson dysphagia inventory; NMES, neuromuscular electrical stimulation; PAS, penetration and aspiration scale; PRT, progressive resistance training; SD, standard deviation; SFSS, swallowing function scoring system; SSA, standardised swallowing assessment; SWAL-QOL, swallowingrelated quality of life; TT, traditional therapy; TTS, thermal-tactile stimulation; VAS, visual analogue scale; VFSS, videofluoroscopic swallowing study Study details Key efficacy findings Key safety findings Comments Heijnen (2012) 6 Randomised controlled trial Netherlands Recruitment period: not reported Study population: patients with Parkinson s disease and oropharyngeal dysphagia. n=109 (NMES at a motor level [NMES-M] vs NMES at a sensory level [NMES-S] vs TT). Numbers randomised not specified. Age: mean 68 Sex: 72.2% male Patient selection criteria: patients between 40 and 80 years with confirmed diagnosis of idiopathic Parkinson s disease who were on an unaltered protocol of antiparkinson s Number of patients analysed: 88 in total; however, numbers varied between outcome measures. Dysphagia severity (measured on a scale from 1 to 100 with higher scores indicating decreasing dysphagia severity) Group Baseline Median (IQR) Increase in score from baseline to posttreatment assessment Median (IQR) P value (for within group change) NMES-M 72 (52-88) 10 (0-31) <0.001 NMES-S 74 (49-87) 6 (-2-24) 0.005 TT 59 (41-88) 19 (3-44) <0.001 No significant differences in the changes in dysphagia severity scores between the three groups (no p values reported). MDADI scores (higher scores indicate a better quality of life) Total Score Baseline Median (IQR) Change in score from baseline to post-treatment assessment Median (IQR) b NMES-M a 69 (63-81) 7 (2-13) -3 (-10-3) NMES-S 74 (65-82) 4 (-1-9) -2 (-11-3) Change in score from post-treatment assessment to 3- month follow-up to Median (IQR) c TT 72 (63-80) 4(-4-8) 1 (-4-6) a The NMES-M group was the only group that exhibited significant changes in total MDADI scores at post-treatment assessment (no p values reported). b No significant differences were observed in the changes in total MDADI scores between groups at post-treatment assessment (no p values reported). C No significant changes in total MDADI scores from post-treatment assessment were observed within groups at 3-month follow-up (no p values reported). No adverse events were reported in the study; however, it is unclear if they were actively monitored. NB: included in the Tan 1 systematic review. Follow-up issues: 21 subjects were excluded: 17 due to changes in antiparkinson s medication; 2 due to dental surgery; 2 due to unspecified reasons. Study design issues: Systematic sampling: method of randomisation was by assigning each consecutive patient to the next treatment group. Potential for information bias: 85 speech therapists were involved in the study. Therapists received training and information on NMES by an experienced laryngologist who was certified to use surface electrical stimulation. Laryngologist and speech language pathologist were present at initial treatment sessions to IP overview: Transcutaneous neuromuscular electrical stimulation for oropharyngeal dysphagia 17 of 47

Abbreviations used: ASHA-NOMS, American speech-language-hearing association national outcome measurement system; CDS, clinical dysphagia scale; DOSS, dysphagia outcome and severity scale; FDS, functional dysphagia scale; FOIS, functional assessment of oral intake; MASA, Mann assessment of swallowing ability; MDADI, MD Anderson dysphagia inventory; NMES, neuromuscular electrical stimulation; PAS, penetration and aspiration scale; PRT, progressive resistance training; SD, standard deviation; SFSS, swallowing function scoring system; SSA, standardised swallowing assessment; SWAL-QOL, swallowingrelated quality of life; TT, traditional therapy; TTS, thermal-tactile stimulation; VAS, visual analogue scale; VFSS, videofluoroscopic swallowing study Study details Key efficacy findings Key safety findings Comments medication for at least 2 months, oropharyngeal dysphagia with preservation of swallowing reflex. Exclusion criteria: other neurological disease, severe cardiopulmonary disease, epilepsy, carotid sinus syndrome, severe mental depression, severe cognitive degeneration, deep brain stimulation or malignancies, received dysphagia treatment within 6 months of enrolment. Technique: NMES groups received TT in conjunction with NMES. The 2 NMES groups differed in the intensity of the electrical current applied. NMES-M group: stimulation occurred at a motor level: NMES was delivered with an electrical current that had a frequency of 80 Hz and pulse width of 700 µs. NMES-S group received stimulation at a sensory level. Groups received 13 15 sessions of half an hour each, for 5 No significant changes in MDADI subscale scores were observed within groups at post-treatment assessment apart from the TT group, which exhibited significant changes in the global assessment subscale (no p values reported). No significant changes in MDADI subscores from post-treatment assessment were observed within groups at 3-month follow-up (no p values reported). SWAL-QOL scores (higher scores indicate a better quality of life) There were no significant changes in any of the SWAL-QOL domains within both NMES groups at post-treatment assessment and at 3-month follow-up. The TT group exhibited a significant improvement in the Symptom domain (median=10, p=0.004) at post-treatment assessment. FOIS scores (higher scores indicate better oral intake) All groups exhibited median scores of 7 (indicating oral intake with no feeding restrictions) at baseline (n=29 patients in all 3 groups). Scores remained unchanged after treatment and at follow-up (no p values reported). ensure the standardised application of NMES. Dysphagia severity: patients were asked to rate the severity of their dysphagia on a scale from 0 to 100: 0 indicated severe dysphagia, 100 indicated normal swallowing. SWAL-QOL assesses the impact of dysphagia on quality of life. Scores range from 0 to 100 with higher scores indicating better quality of life. MDADI evaluates the impact of dysphagia on the quality of life of patients with head and neck cancer. Scores range from 20 to 100, with higher scores indicating better quality of life. FOIS is a 7- item scale that assesses oral intake with 0 indicating no oral intake and 7 indicating oral intake with no feeding restrictions. Other issues: IP overview: Transcutaneous neuromuscular electrical stimulation for oropharyngeal dysphagia 18 of 47

Abbreviations used: ASHA-NOMS, American speech-language-hearing association national outcome measurement system; CDS, clinical dysphagia scale; DOSS, dysphagia outcome and severity scale; FDS, functional dysphagia scale; FOIS, functional assessment of oral intake; MASA, Mann assessment of swallowing ability; MDADI, MD Anderson dysphagia inventory; NMES, neuromuscular electrical stimulation; PAS, penetration and aspiration scale; PRT, progressive resistance training; SD, standard deviation; SFSS, swallowing function scoring system; SSA, standardised swallowing assessment; SWAL-QOL, swallowingrelated quality of life; TT, traditional therapy; TTS, thermal-tactile stimulation; VAS, visual analogue scale; VFSS, videofluoroscopic swallowing study Study details Key efficacy findings Key safety findings Comments Freed (2001) 7 Non-randomised comparative study USA Recruitment period: 1993 5 Study population: patients with dysphagia following a stroke n=110 (NMES vs TTS. Numbers allocated to each group not reported) Mean age: NMES group: 75.7 years, TTS group: 78.1 years. Sex: NMES group: 56% male, TTS group: 52% male Patient selection criteria: in patients or outpatients with primary diagnosis of stroke and confirmed swallowing disorder by Modified Barium Number of patients analysed: 99 (63 NMES vs 36 TTS) SFSS scores (higher scores indicate decreasing dysphagia severity) Baseline (mean±sd) Follow-up (mean±sd) NMES 0.8±1.0 4.5±1.7 TTS 0.8±1.2 1.3±1.1 The Wilcoxon signed rank test revealed that SFSS scores improved significantly in both groups (NNMES group p<0.0001, TTS group p=0.05). The Mann-Whitney U test revealed that the NMES group had significantly greater improvements in SFSS scores compared with the TTS group (p<0.0001). Successful treatment (n patients with swallow scores 0 and 1 at baseline): NMES % (n/n) Achievement of swallow score 2 95 or higher (PEG not needed) a (41/42) TTS % (n/n) 52 (15/29) P value <0.0001 Achievement of complete 35 0 <0.0002 swallow score of 6 b 89% of NMEs patients and 67% of TTS patients retained their posttreatment SFSS score at 2-year follow-up (no p value reported). Study reported that there were no occurrences of laryngospasm or change in heart rhythm. NB: included in the Tan 1 systematic review. Follow-up issues: 11% (11/99) of patients were lost to follow-up. Reasons included drug toxicity from other treatments (6), transfer to other hospitals (2) or not reported (3). Study design issues: Patients were alternately assigned to the treatment groups. 3 radiologists assessed modified barium swallowing videos and assigned patients swallowing scores. SFSS evaluates the severity of dysphagia. A score of 0 indicates severe dysphagia where no solid or liquid is safe to swallow. A score of 6 indicates no swallowing deficit where all liquids are tolerated. Study population issues: Patients in the NMES group had been treated much longer after IP overview: Transcutaneous neuromuscular electrical stimulation for oropharyngeal dysphagia 20 of 47

Abbreviations used: ASHA-NOMS, American speech-language-hearing association national outcome measurement system; CDS, clinical dysphagia scale; DOSS, dysphagia outcome and severity scale; FDS, functional dysphagia scale; FOIS, functional assessment of oral intake; MASA, Mann assessment of swallowing ability; MDADI, MD Anderson dysphagia inventory; NMES, neuromuscular electrical stimulation; PAS, penetration and aspiration scale; PRT, progressive resistance training; SD, standard deviation; SFSS, swallowing function scoring system; SSA, standardised swallowing assessment; SWAL-QOL, swallowingrelated quality of life; TT, traditional therapy; TTS, thermal-tactile stimulation; VAS, visual analogue scale; VFSS, videofluoroscopic swallowing study Study details Key efficacy findings Key safety findings Comments Kushner (2013) 8 Non-randomised comparative study Recruitment period: 2005 2011 Study population: patients with pharyngeal dysphagia following an acute stroke n=92 (65 NMES+TT+PRT vs 27 TT+PRT) Age: range 19 91 years Sex: 58.7% male Patient selection criteria: adults who had new onset haemorrhagic or ischaemic stroke and severe to profound oropharyngeal dysphagia (high risk of aspiration of solids and/or liquids of any consistency, including saliva), an initial FOIS score of 3 or lower, required nutritional support by percutaneous gastrostomy feeding Number of patients analysed: 92 (65 NMES+TT+PRT vs 27 TT+PRT) FOIS scores (higher scores indicate better oral intake) Group Final score Mean increase Proportion of patients with FOIS score 5 7 [minimal or no feeding restrictions] at follow-up NMES+TT+PRT 5.1 4.4 46% (30/65) TT+PRT 3.3 2.4 26% (7/27) P value N/A <0.001 0.01 NB: all participants had FOIS scores below 3; however, mean baseline FOIS scores were not reported Statistically significant differences were observed in initial FOIS scores between groups: NMES+TT+PRT group exhibiting worse initial FOIS scores (mean rank 42.64) in compared with the TT+PRT group (mean rank 55.8) [z=-2.4; p=0.015]. Significant differences were observed in improvements in the swallowing scores in the NMES+TT+PRT group in comparison to the TT+PRT group (z=3.6: p<0.001) At follow-up, 46% (30/65) of patients in the NMES+TT+PRT group had minimal or no swallowing restrictions (FOIS scores 5 7) whereas 26% (7/27) of the TT+PRT group had minimal or no swallowing restrictions (P=0.01) The occurrence of adverse events was actively sought but none were reported in the study. NB: not included in the Tan 1 systematic review. Follow-up issues: No follow-up period reported. Study design issues: FOIS is a 7-item scale that assesses oral intake with 0 indicating no oral intake and 7 indicating oral intake with no feeding restrictions. Study population issues: Other: NMES+TT+PRT group had statistically worse initial FOIS scores in comparison with the TT+PRT group. Poor reporting of outcome measures: authors did not report mean baseline FOIS scores and results were not tabulated. IP overview: Transcutaneous neuromuscular electrical stimulation for oropharyngeal dysphagia 22 of 47