Stimulation Therapy In Patients Research Articles

Longitudinal EpiTrack assessment of executive functions following vagus nerve stimulation therapy in patients with drug-resistant epilepsy.

To investigate executive functions and attention with repeated EpiTrack evaluations in a group of DR patients with drug-resistant epilepsy (DRE) receiving vagus nerve stimulation (VNS) during a follow-up duration of up to 5 years. The study involved 33 patients with DRE who were assessed with EpiTrack as a part of the clinical VNS protocol. Evaluations were scheduled prior to VNS implantation and then at 6 months, 12 months, and yearly thereafter. However, the COVID-19 pandemic disrupted follow-up. Therefore, changes in EpiTrack total scores over time were analyzed using a linear mixed-effects (LMEs) model to compensate for the variation in follow-up duration when predicting EpiTrack total score changes over 5 years. The median follow-up time was 29 months. During each month, the EpiTrack total score was predicted to increase by 0.07 units (95% confidence interval [CI]: 0.01-0.12, P = 0.02), corresponding to a change from a baseline score of 27.3 (severe impairment) to a score of 28.9 (mild impairment) at 2 years and a score of 31.5 (almost normal) at 5 years. In the group of patients with psychiatric comorbidities, the EpiTrack total score increased by 0.14 units per month (P = 0.003), which was 3.5-fold higher than the increase of patients without psychiatric comorbidities. For the patients taking 1-2 antiseizure medications (ASMs), the EpiTrack total score increased by 0.11 units per month (P = 0.005), which was almost quadruple the rate of patients taking 3-4 ASMs. Based on EpiTrack total scores, the LME model predicted a four-point improvement in executive functions among patients with DRE at 5 years after the initiation of VNS, representing a clinically meaningful change. DRE patients with comorbid depression seemed to experience the most cognitive benefits. In addition, better cognitive outcomes were achieved if the patient took less than three ASMs. Executive functions and attention may improve during vagus nerve stimulation therapy in patients with drug-resistant epilepsy. Epilepsy patients who have depression or use fewer than three antiseizure medications are likely to benefit cognitively more from the treatment.

Reduced usage of upper airway stimulation therapy in patients with comorbid insomnia and obstructive sleep apnea.

Upper airway stimulation (UAS) is a hybrid surgical-medical device used to treat moderate-to-severe obstructive sleep apnea (OSA). Comorbid insomnia and OSA (COMISA) is present in ∼50% of these patients. Our aim was to study UAS outcomes and adherence in patients with COMISA. A retrospective review of 379 patients with OSA who underwent UAS implantation at a single institution between 2014 and 2021. Demographics, OSA severity metrics, and insomnia data were collected. Patients were categorized into OSA alone (OSAa) or COMISA. Objective adherence data were collected from device downloads during follow-up. Data were analyzed with using R Studio (R Foundation for Statistical Computing, Vienna, Austria) and Prism (Boston, MA, USA). Of the 274 patients included, 148 had COMISA (54.0%) and 126 OSAa (46.0%). Average follow-up time was 2.5 years and OSAa had more males than COMISA (P < .001). Patients with COMISA had higher insomnia severity index scores than OSAa preoperatively (16 vs 8.7; P = .003). All groups showed significant decreases in objective and self-reported OSA outcomes postoperatively, but there was no difference between COMISA and OSAa. Patient with COMISA had decreased device usage (4.9 vs 5.8 h/night; P = .015) and paused therapy more often than patients with OSAa (1.4 vs 0.4 pauses/night; P < .001). Multivariate linear regression, when controlling for sex as a covariate, showed insomnia to be an independent predictor of lower UAS hours/night and more pauses/night (P < .01). Patients with COMISA use UAS therapy for shorter durations and require more breaks from therapy when compared with those with OSAa. Future research is needed to explore the underlying mechanism and improve UAS treatment adherence in patients with COMISA. Kaffenberger TM, Chandna M, Kaki P, etal. Reduced usage of upper airway stimulation therapy in patients with comorbid insomnia and obstructive sleep apnea. J Clin Sleep Med. 2023;19(12):1997-2004.

Somatosensory Stimulation Therapy in Patients with Somatosensory Tinnitus: A Pilot Study.

To explore the efficacy and safety of EMS (Exercise to improve muscle strength, Motion of joints, and Stretch training) in somatosensory tinnitus symptoms. A randomized delayed-start controlled trial. At the Department of Otorhinolaryngology, Eye and Ear, Nose, and Throat Hospital between February 2019 and May 2019. Patients with somatosensory tinnitus. In the immediate-start group, the participants received EMS somatosensory stimulation therapy for 3 weeks and were followed up for 3 weeks. In the delayed-start group, the participants first waited for 3 weeks and were treated with EMS somatosensory stimulation therapy for 3 weeks. The primary endpoint was the changes in Tinnitus Handicap Inventory (THI) and the visual analog scale (VAS) scores after 3 weeks of treatment. The secondary endpoint was the proportion of patients achieving improvements in VAS and THI scores. THI and VAS were collected at baseline and at 3, 6, 9, and 12 weeks. Sixty-four patients were randomized to the immediate-start group and delayed-start treatment with each 32. After the 3-week treatment, the immediate-start group showed significant lower in VAS (25.7 ± 3.3 versus 38.9 ± 5.8, p < 0.001) and THI (29.1 ± 5.1 versus 42.8 ± 6.6, p < 0.001). There were no differences in VAS and THI between the two groups after treatment (i.e., at weeks 6, 9, and 12). All patients were followed up for 6, 9, and 12 weeks, and the therapeutic effect was stable. The EMS somatosensory stimulation therapy might be an effective and safe treatment for improving symptoms, and the therapeutic effect was still stable in 3, 6, 9, and 12 weeks. ChiCTR1900020746.

Anti-Inflammatory Effects of Two-Week Sacral Nerve Stimulation Therapy in Patients With Ulcerative Colitis

Background and AimsSacral nerve stimulation (SNS) showed anti-inflammatory properties in animal models of inflammatory bowel disease. We aimed to evaluate the effectiveness and safety of SNS in patients with ulcerative colitis (UC). Materials and MethodsTwenty-six patients with mild and moderate disease were randomized into two groups: SNS (delivered at S3 and S4 sacral foramina) and sham-SNS (delivered 8–10 mm away from sacral foramina), with the therapy applied once daily for one hour, for two weeks. We evaluated the Mayo score and several exploratory biomarkers, including C-reactive protein in the plasma, pro-inflammatory cytokines and norepinephrine in the serum, assessment of autonomic activity, and diversity and abundance of fecal microbiota species. ResultsAfter two weeks, 73% of the subjects in the SNS group achieved clinical response, compared with 27% in the sham-SNS group. Levels of C-reactive protein, pro-inflammatory cytokines in the serum, and autonomic activity were significantly improved toward a healthy profile in the SNS group but not in the sham-SNS group. Absolute abundance of fecal microbiota species and one of the metabolic pathways were changed in the SNS group but not in the sham-SNS group. Significant correlations were observed between pro-inflammatory cytokines and norepinephrine in the serum on the one side and fecal microbiota phyla on the other side. ConclusionsPatients with mild and moderate UC were responsive to a two-week SNS therapy. After performing further studies to evaluate its efficacy and safety, temporary SNS delivered through acupuncture needles may become a useful screening tool for identifying SNS therapy responders before considering long-term implantation of the implantable pulse generator and SNS leads for performing long-term SNS therapy.

Activation of healing and reduction of pain by single-use automated microcurrent electrical stimulation therapy in patients with hard-to-heal wounds.

Evidence shows that Electrical Stimulation Therapy (EST) accelerates healing and reduces pain, but EST has yet to become widely used. One reason is the historical use of complex, clinic-based EST devices. This evaluation assessed the early response of different hard-to-heal wounds to a simple, wearable, single-use, automated microcurrent EST device (Accel-Heal, Accel-Heal Technologies Limited - Hever, UK). Forty wounds (39 patients: 18 female - 21 male), mean age 68.9 ± 14.0 years comprised of: seven post-surgical, three trauma, 12 diabetic foot (DFU), 10 venous (VLU), four pressure injuries (PI), four mixed venous or arterial ulcers (VLU/arterial) received automated microcurrent EST for 12 days. Early clinical responses were scored on a 0-5 scale (5-excellent-0-no response). Pain was assessed at 48 h, seven days, and 14 days on a 0-10 visual analogue scale (VAS). Overall, 78% of wounds showed a marked positive clinical response (scores of 5 and 4). Sixty eight percent of wounds were painful with a mean VAS score of 5.5. Almost every patient (96%) with pain experienced reduction within 48 h. All patients with painful wounds experienced pain reduction after seven days: 2.50 VAS (45% reduction) and further pain reduction after 14 days: 1.83 VAS (33%).

Behavioral Change Prediction from Physiological Signals Using Deep Learned Features.

Predicting change from multivariate time series has relevant applications ranging from the medical to engineering fields. Multisensory stimulation therapy in patients with dementia aims to change the patient’s behavioral state. For example, patients who exhibit a baseline of agitation may be paced to change their behavioral state to relaxed. This study aimed to predict changes in one’s behavioral state from the analysis of the physiological and neurovegetative parameters to support the therapist during the stimulation session. In order to extract valuable indicators for predicting changes, both handcrafted and learned features were evaluated and compared. The handcrafted features were defined starting from the CATCH22 feature collection, while the learned ones were extracted using a temporal convolutional network, and the behavioral state was predicted through bidirectional long short-term memory auto-encoder, operating jointly. From the comparison with the state of the art, the learned features-based approach exhibits superior performance with accuracy rates of up to 99.42% with a time window of 70 seconds and up to 98.44% with a time window of 10 seconds.

Biomarkers for Chronic Neuropathic Pain and Their Potential Application in Spinal Cord Stimulation (SCS) Therapy

Chronic neuropathic pain disorders represent a common long-term disability globally. Its treatment has limited success because of its poorly understood mechanisms. Moreover, the effectiveness of neuropathic pain management regimens and procedures have been difficult to determine to date, due to the subjectivity related to pain perception, and a lack of standardized assessment of neuropathic pain. However, one of the most effective and popular management strategies of chronic neuropathic pain in recent times is spinal cord stimulation (SCS), a form of neuromodulation. This review aims to understand which substances inside the human body increase and decrease with increasing neuropathic pain. Through identifying those biomarkers and finding correlations between neuropathic pain and those components, we would like to apply our knowledge to develop a biomarker profile which will ultimately help to see prognosis or predict success of spinal cord stimulation therapy in patients suffering from chronic neuropathic pain.&#x0D; CBMJ 2021 January: vol. 10 no. 02 P: 118-122

Research on the application effect of cognitive stimulation therapy in patients with Alzheimer's disease based on expert consultation and semistructured interviews.

The awareness and utilization of psychological therapies for Alzheimer's disease have increased significantly in recent years. Limitations on the utilization of pharmacological therapy for Alzheimer's disease in China have corresponded with this surge in greater studies in the field. For individuals who have Alzheimer's disease, cognitive stimulation therapy (CST) is a quick self-help that is founded on the theories of quality and cognitive functioning. People with Alzheimer's disease often participate in cognitive behavioral programs; however, their expense has never been studied. Being part of a meta-analysis, we analyze the application effectiveness of a CST program that is based on recent research for Alzheimer's disease patients. A CST group therapy was given to 91 Alzheimer's patients, who resided in healthcare settings or the general public, multiple times per week for 8 weeks; the other 70 people with Alzheimer's disease got a medical therapy. Costs were computed, and resource utilization was tracked for 8 weeks both before and after the therapy. It was determined by a value study. In the value study, cognition and quality of life were the major and tertiary outcomes, respectively. Contours of cost-effectiveness and acceptance were drawn. It was driven based on expert consultation and semistructured interviews. In Alzheimer's disease, CST improves intelligence and standard of living, and there was no difference in implementation expenditures between the categories. Regarding both outcome metrics, there is a significant chance that CST seems to be more expensive than conventional therapy within realistic expectations. The efficacy of CST for Alzheimer's patients is superior to conventional treatment, and it could be the greater value. The outcomes contrast well with pharmacological studies for Alzheimer's. Many people with Alzheimer's disease may benefit significantly from CST groups.

Effects of gamma sensory stimulation on cognitive function in Alzheimer’s disease patients

AbstractBackgroundAlzheimer’s disease (AD) patients exhibit distorted excitatory‐inhibitory balance of neuronal activity, leading to accelerated worsening of functional and cognitive abilities. Improving abnormal neuronal synchrony by long‐term non‐invasive, gamma sensory stimulation at 40 Hz in transgenic mice carrying pathological AD human genes has been shown to beneficially affect neural activity and improve learning and memory. In the present translational clinical trial, the effects of gamma sensory stimulation on cognition and global function were evaluated in AD patients using an at‐home therapy device (Cognito Therapeutics, Cambridge, MA).MethodThe phase I/II randomized, controlled, single‐blinded multi‐center clinical trial (Overture study; NCT03556280) evaluated safety, adherence rates and efficacy of gamma sensory stimulation therapy in patients with mild to moderate Alzheimer’s disease (MMSE 14‐26, inclusive). The 6‐month trial included treatment and sham groups receiving daily, one‐hour sensory stimulation but only participants in the treatment group were exposed to 40Hz auditory and visual stimulations. During the trial, cognitive functions were measured by Alzheimer's Disease Assessment Scale (ADAS‐Cog), Mini‐Mental State Examination (MMSE), and Clinical Dementia Rating Sum of Boxes (CDR‐SB). In order to align assessment data in time to study events (therapy start and end) and account for variable study visit intervals at start and end of therapy period, cognitive measures were calculated on a per‐patient basis by a model of AD‐related cognitive decline derived from a large‐scale dataset. Finally, adjusted cognitive scores were compared between the two groups.ResultThe trial has been completed by 33 and 19 patients in the treatment and sham groups, respectively. Daily therapy of gamma sensory stimulation was well tolerated, confirming safety and high adherence. The three independent cognitive tests demonstrated a diminished cognitive decline in the treatment group compared to the sham group. Final analysis results from MMSE, ADAS‐Cog, CDR‐SB and Integrated Alzheimer's Disease Rating Scale (iADRS) will be presented at the meeting.ConclusionThe present findings, together with the established safety profile, functional benefit, and improvement in sleep justify further evaluation of gamma sensory stimulation in AD patients.

Comparison of the Efficiency of High-Intensity Laser Therapy and Transcutaneous Electrical Nerve Stimulation Therapy in Patients With Symptomatic Temporomandibular Joint Disc Displacement With Reduction

Many different treatment modalities have been tried in the treatment of temporomandibular joint (TMJ) disorders and different results have been reported. The aim of the study was to investigate and compare the effects of high-intensity laser therapy (HILT) and transcutaneous electrical nerve stimulation (TENS) therapy on the treatment of patients with TMJ disc displacement with reduction(DDWR). Researchers conducted a prospective, single-blind, controlled clinical trial on patients with TMJ disc disease at a university's oral and maxillofacial surgery clinic. One hundred two patients were randomized into 3 groups (HILT, TENS and control group). The patients were evaluated in terms of maximum mouth opening (MMO), assisted MMO, Visual Analog Scale (VAS) (pain), and VAS (function). In addition, the disability status of the patients with the Jaw Functional Limitation Scale-20 (JFLS-20) and the quality-of-life with the Oral Health Impact Profile (OHIP-14) was evaluated. At the start of the trial, in terms of socio-demographic characteristics, no significant differences existed between the groups. Significant improvements were seen in pain (VAS), MMO, total JFLS-20 and total OHIP-14 scores in the HILT and TENS groups compared to the control group. At week 4, the VAS pain score decreased significantly in the HILT group compared to the TENS group (48 and 25%, respectively), while the MMO was significantly increased (24 and 10%, respectively). In addition, there was a significant improvement in both the total JFLS-20 score and the total OHIP-14 score at weeks 4 and 12 in the HILT group compared to the TENS group (P < .05). It was observed that the healing effect of pulsed Nd: YAG laser therapy was significantly higher than TENS in patients with DDWR. Therefore, HILT should be a priority option over TENS therapy in patients with disc displacement.

"Brain Stimulation Therapy in Patients with Parkinson’s Disease"

"Brain Stimulation Therapy in Patients with Parkinson’s Disease"

Socioeconomic Disparities in the Utilization of Spinal Cord Stimulation Therapy in Patients with Chronic Pain.

Spinal cord stimulation (SCS) therapies are used in the management of patients with complex regional pain syndrome I (CRPS I) and failed back surgery syndrome (FBSS). The purpose of this study was to investigate the racial and health insurance inequalities with SCS therapy in patients with chronic pain who had CRPS I and FBSS. Patients with chronic pain who had a discharge diagnosis of FBSS and CRPS I were identified using the National Inpatient Sample database. Our primary outcome was defined as the history of SCS utilization by race/ethnicity, income quartile, and insurance status. Multivariable logistic regression was used to determine the variables associated with utilization of SCS therapy. Between 2011 and 2015, 40,858 patients who were hospitalized with a primary diagnosis of FBSS and/or CRPS I were identified. Of these patients, 1,082 (2.7%) had a history of SCS therapy. Multivariable regression analysis revealed that compared to White patients, Black and Hispanic patients had higher odds of having SCS therapy (Black patients: odds ratio [OR]=1.41; 95% confidence interval [CI], 1.12 to 1.77; P=0.003; Hispanic patients: OR=1.41; 95% CI, 1.10 to 1.81; P=0.007). Patients with private insurance had significantly higher odds of having SCS therapy compared with those with Medicare (OR=1.24; 95% CI, 1.08 to 1.43; P=0.003). Compared to patients with Medicare, Medicaid patients had lower odds of having SCS therapy (OR=0.50; 95% CI, 0.36 to 0.70; P<0.001). Our study suggests that socioeconomic disparities may exist in the utilization of SCS among hospitalized patients with CRPS I and FBSS the United States. However, confirming these data from other administrative databases, in the outpatient setting, may shed more insight.

Application of intracranial lead reconstruction in deep brain stimulation therapy in patients with Parkinson's disease

To evaluate the feasibility of applying intracranial lead reconstruction in deep brain stimulation (DBS) therapy for Parkinsonism. We retrospectively collected the clinical data from 27 patients with Parkinson's disease (PD), who received bilateral subthalamic nucleus (STN) DBS therapy between January, 2016 and December, 2017. According to the position of the selected optimal stimulating contact of the implanted leads, the patients were divided into group A with the stimulating contacts of the bilateral leads in the STN, group B with unilateral stimulating contacts in the STN, and group C with bilateral stimulating contacts outside the STN. All the patients were assessed for improvement using Hoehn-Yahr stage, the third part of United Parkinson's Disease Rating Scale (UPDRS Ⅲ), Schwab and England Activities of Daily Living (SE-ADL), and L-dopa equivalent daily dose (LEDD). The consistency between the optimal stimulating contact selected by lead reconstruction and that by standard postoperative programming procedure was also evaluated. The patients in all the 3 groups showed postoperative improvements in Hoehn-Yahr stage, UPDRS Ⅲ score, SE-ADL score, and LEDD in the medication-off state. But at 12 months of the follow-up, such improvements were maintained only in the patients of group A. The optimal stimulating contacts selected by lead reconstruction and standard postoperative programming procedure had a matching rate of up to 77.78% (42/54), and the coordinates of the optimal contacts selected by the two methods showed no significant difference. Intracranial lead reconstruction facilitates the study of the association between the implant site of the leads and the clinical outcome of DBS therapy for PD and allows the precise selection of the optimal contact of the implanted leads in postoperative programming of DBS.

Low Pulvinar Intensity in Susceptibility-Weighted Imaging May Suggest Cognitive Worsening After Deep Brain Stimulation Therapy in Patients With Parkinson's Disease.

Purpose: Deep brain stimulation (DBS) is an established therapy for Parkinson's disease (PD). However, deteriorating cognitive function after DBS is a considerable problem for affected patients. This study was undertaken to assess whether pulvinar findings in susceptibility-weighted imaging (SWI) can suggest cognitive worsening.Methods: We examined 21 patients with PD who underwent DBS along with SWI and neuromelanin-sensitive MR imaging (NMI). We further assessed pulvinar hypointensity based on the SWI findings and also the area of the substantia nigra (SN) pars compacta in NMI. We then examined associations among cognitive changes, pulvinar hypointensity, and SN area. The cognitive function of the patient immediately before surgery was compared with function at 1 year postoperatively.Results: Pulvinar hypointensity in SWI was found in 11 of 21 patients with PD at baseline. One year postoperatively, six of the 21 patients demonstrated a Mini-Mental State Examination score that was ≥3 points lower than the baseline score. We observed pulvinar hypointensity in SWI before DBS surgery in five of these six patients (p = 0.072). During the first postoperative year, six of 21 patients reported both transient or permanent hallucinations; we observed pulvinar hypointensity in these six patients, while 10 patients without pulvinar hypointensity had no hallucinations.Conclusion: Pulvinar hypointensity in SWI in patients with PD may provide information that is useful for suggesting cognitive deterioration after DBS treatment.

Effectiveness of neuromuscular electrical stimulation therapy in patients with urinary incontinence after stroke: A randomized sham controlled trial.

Background:This study aimed to evaluate the effectiveness of neuromuscular electrical stimulation (NMES) therapy in patients with urinary incontinence after stroke (UIAS).Methods:A total of 82 patients with UIAS were randomly assigned to 2 groups that received NMES therapy (NMES group) or sham NMES (sham group) for 10 weeks. The primary efficacy endpoints were measured by urodynamic values, and Overactive Bladder Symptom Score (OABSS). The secondary efficacy endpoints were assessed by International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) score, Barthel Index (BI) scale, and adverse events. All outcomes were evaluated at baseline and at the end of 10 weeks treatment.Results:After 10-week treatment, the patients received NMES therapy showed better efficacy in primary endpoints of urodynamic values (P <.01) and OABSS (P <.01), and secondary endpoints of ICIQ-SF (P <.01) and BI (P <.01), compared with patients who underwent sham NMES. No adverse events were recorded in both groups.Conclusions:In summary, we demonstrated that 10 weeks of NMES therapy was efficacious in patients with UIAS.

Comparing the efficacy of targeted spinal cord stimulation (SCS) of the dorsal root ganglion with conventional medical management (CMM) in patients with chronic post-surgical inguinal pain: the SMASHING trial

BackgroundA significant number of patients who undergo a standard inguinal hernia repair or a Pfannenstiel incision develop chronic (> 3 months) post-surgical inguinal pain (PSIP) due to nerve entrapment. If medication or peripheral nerve blocks fail, surgery including neurectomies may offer relief. However, some patients do not respond to any of the currently available remedial treatment modalities.Targeted spinal cord stimulation (SCS) of the dorsal root ganglion (DRG) is a relatively new type of therapy that has a potential to significantly reduce chronic PSIP. The Axium® SCS System (Spinal Modulation Inc., NY, USA) has been shown to be safe and successful in small cohorts of PSIP patients.Aim of this study is to evaluate targeted spinal cord stimulation therapy in patients with PSIP.MethodsA prospective, multicentre, randomized controlled trial with optional one-way crossover will assess the efficacy of the Axium® SCS system for the treatment of PSIP. Seventy-eight patients with intractable PSIP following open hernia repair or Pfannenstiel incision who did not respond favorably to previous pain treatment regimens including a neurectomy will be randomized to either an Axium® SCS arm or a control arm receiving only conventional medical management (CMM).Primary outcome is the difference in percentage of subjects with ≥50% pain relief after 6 months using a Numerical Pain Rating Scale (NPRS). Data are collected using a daily pain/sleep diary and a number needed to treat (NNT) analysis is performed. Various secondary outcomes will be collected.DiscussionTargeted SCS stimulation of the DRG using the Axium® SCS system will possibly offer significant pain reduction in patients with PSIP who are refractory to other treatment modalities.Trial registrationThe study protocol is registered at the NIH Clinical Trials Registry (http://clinicaltrials.gov, ClinicalTrials.gov identifier: NCT02349659) on January 29, 2015.

Anatomic predictors of response and mechanism of action of upper airway stimulation therapy in patients with obstructive sleep apnea.

Upper airway stimulation has been shown to be an effective treatment for some patients with obstructive sleep apnea. However, the mechanism by which hypoglossal nerve stimulation increases upper airway caliber is not clear. Therefore, the objective of this study was to identify the mechanism of action of upper airway stimulation. We hypothesized that, with upper airway stimulation, responders would show greater airway opening in the retroglossal (base of the tongue) region, greater hyoid movement toward the mandible, and greater anterior motion in the posterior, inferior region of the tongue compared with nonresponders. Seven participants with obstructive sleep apnea who had been successfully treated with upper airway stimulation (responders) and six participants who were not successfully treated (nonresponders) underwent computed tomography imaging during wakefulness with and without hypoglossal nerve stimulation. Responders reduced their apnea-hypopnea index (AHI) by 22.63 ± 6.54 events per hour, whereas nonresponders had no change in their AHI (0.17 ± 14.04 events per hour). We examined differences in upper airway caliber, the volume of the upper airway soft tissue structures, craniofacial relationships, and centroid tongue and soft palate movement between responders and nonresponders with and without hypoglossal nerve stimulation. Our data indicate that compared with nonresponders, responders had a smaller baseline soft palate volume and, with stimulation, had (1) a greater increase in retroglossal airway size; (2) increased shortening of the mandible-hyoid distance; and (3) greater anterior displacement of the tongue. These results suggest that smaller soft palate volumes at baseline and greater tongue movement anteriorly with stimulation improve the response to upper airway stimulation.

PMD76 - A Preliminary Cost-Utility Analysis of Non-Invasive Vagus Nerve Stimulation Therapy in Patients Suffering with Headache and Functional Disorder Multi-Morbidity

Headache is a highly prevalent disorder that is often associated with a wide range of functional multi-morbidities (Errico, 2014). In primary care it is typical for each condition to be treated in isolation, and as a result multi-morbid patients place a huge burden on the health system. The aim of this project was to develop a de novo early economic model to assess the cost-utilty of using a non-invasive vagus nerve stimulation (nVNS) therapy in primary care, for patients suffering with headache and multi-morbidity. The cost-utility analysis was conducted from the perspective of the English National Health Service, utilising EQ-5D-5L and healthcare resource data collected from nVNS primary care clinics designed to treat multi-morbid patients (n=233). Resource utilisation data were combined with unit cost data to determine the cost implications of multi-morbid patients either with, or without, the use of nVNS. The primary output of the model was an estimated incremental cost-effectiveness ratio (ICER) comparing nVNS + standard care, to standard care alone over a 12 month period. Net monetary and net health benefit were also calculated. Due to uncertainty in input parameters, extensive deterministic sensitivity analyses were conducted. The preliminary analysis estimated an ICER of £8,310 per quality-adjusted life year (QALY) gained when comparing nVNS + standard of care, to standard of care alone. Furthermore, a net monetary benefit of £1,112 and a net health benefit of 0.10 QALYs gained were calculated based upon a £20,000 per QALY threshold. Improvement in utility score with nVNS was the key driver of the analysis. The preliminary results of the economic evaluation of nVNS compared with standard care suggest that gammaCore is a cost-effective treatment for patients with multi-morbidity from the perspective of the NHS.

Inhibition and Excitation of Bladder Function by Tibial Nerve Stimulation Using a Wirelessly Powered Implant: An Acute Study in Anesthetized Cats

Tibial nerve stimulation is a minimally invasive neuromodulation treatment of overactive bladder. However, in addition to our limited understanding of the underlying mechanisms, there are also questions regarding the long-term delivery of tibial nerve stimulation therapy in patients. We aimed to characterize the effects of stimulation frequency using a wirelessly powered implantable stimulation device. Six α-chloralose anesthetized adult male cats were used in this study. A multicontact lead was surgically implanted subcutaneously in the hind limb and used to stimulate the tibial nerve. Using an isovolumetric bladder a short duration of electrical pulses was applied at amplitudes 3 times the motor threshold and at frequencies from 2 to 20 Hz. Implant driven stimulation of the tibial nerve resulted in frequency dependent activation of bladder reflexes. Low frequency tibial nerve stimulation (2 Hz) consistently evoked excitatory responses (mean ± SE 32.9% ± 3.8%). In contrast, higher frequency tibial nerve stimulation (6 to 20 Hz) inhibited bladder function (overall mean 14.9% ± 2.4%). Although low foot motor thresholds were achieved at initial implantation (mean 0.83 ± 0.05 mA), a notable elevation in threshold amplitude was observed 5 hours after implantation. To our knowledge this study provides the first evidence of frequency dependent modulation of bladder function in anesthetized cats. The inhibitory influence of tibial nerve stimulation at frequencies above 6 Hz transitioned to an excitatory effect at 2 Hz. Taken together these preclinical data support the feasibility of using a wirelessly powered implantable device to potentially modulate bladder function in patients.

The effectiveness of transcutaneous electrical neural stimulation therapy in patients with urinary incontinence resistant to initial medical treatment or biofeedback

While there are many options for children with treatment refractory urinary incontinence, there is no single accepted method. This study's aim was to prospectively evaluate the effect of transcutaneous electrical nerve stimulation in children with urinary incontinence resistant to standard medical, urological therapy and/or biofeedback. This study was performed at a university hospital. For inclusion, patients >5 years of age first underwent evaluation with urinary ultrasonography, uroflow-electromyogram and voiding diaries. Treatment with biofeedback, alpha adrenergic blockers, anticholinergics and/or urotherapy was commenced according to uroflow-EMG and voiding diary findings. Patients with partial or no response to this standard therapy were then included in this study, performed between April 2012 and February 2014. Patients with anatomical or neurological causes for urinary incontinence were excluded. TENS was performed on S3 dermatome, every day for 3 months. Each session lasted 20 min with a frequency of 10 Hz and generated pulse of 350 μs. Intensity was determined by the child's sensitivity threshold. Medical treatment and urological therapy was continued during TENS. Uroflow parameters (voiding volume as percentage of expected bladder capacity, Qmax, Qave, flow and voiding time, postvoiding residual urine) and urinary system symptoms (presence of urinary tract infection, frequency, urge incontinence, fractionated voiding and constipation) were compared immediately before commencement and immediately after the completion of 3 months of TENS. Twenty-seven patients were included in this study (4 males, 23 females). Patients' average age was 7.2 years, 11 had overactive bladder and 16 had dysfunctional voiding. Comparison of urinary system symptoms and uroflow parameters before and after TENS are shown in Table. After 3 months of TENS; a statistically significant decrease was observed in the number of patients with frequency, urge incontinence, urinary tract infections and constipation. There was a decrease in the number of patients with fractionated voiding, although this change was not statistically significant. Similarly, for uroflow-EMG parameters; bladder capacity, Qmax, Qave and flow time increased while voiding time and PVR decreased. Changes seen in bladder capacity, Qmax and PVR were statically significant, while other changes were not. Patients' response rates after 3 months of TENS were; complete response in 70.4%, partial response in 22.2% and no response in 7.4%. This study has shown that transcutaneous electrical nerve stimulation is a promising treatment option for standard-treatment refractory children with urinary incontinence.