Treatment-Resistant Late-Life Depression: A Review of Clinical Features, Neuropsychology, Neurobiology, and Treatment.

Major depression is common in older adults (≥ 60 years of age), termed late-life depression (LLD). Up to 30% of these patients will have treatment-resistant late-life depression (TRLLD), defined as depression that persists despite two adequate antidepressant trials. TRLLD is challenging for clinicians, given several etiological factors (eg, neurocognitive conditions, medical comorbidities, anxiety, and sleep disruption). Proper assessment and management is critical, as individuals with TRLLD often present in medical settings and suffer from cognitive decline and other marks of accelerated aging. This article serves as an evidence-based guide for medical practitioners who encounter TRLLD in their practice.

Neuromodulation and Opioid Use Disorder: Ethical Opportunities for Canada.

Despite increased efforts of government and non-government organisations to intervene via harm reduction and education initiatives, the opioid crisis has continued to worsen and has been exacerbated by the COVID-19 pandemic. In British Columbia, Canada, opioid overdose deaths in 2021 are the highest ever recorded. Neuromodulation procedures such as deep brain stimulation and repetitive transcranial magnetic stimulation have gained traction as treatments for opioid use disorder in various countries such as Germany, the Netherlands, the United States and China. However, these treatment options have been met with apprehension from both clinicians and patients, likely owing to fear, stigma and reluctance to label addiction as a brain disorder. Further complicating this landscape are socio-demographic factors, as marginalised communities are disproportionately burdened by addiction, while having poor access to care and a history of distrust in the health system. This multifactorial challenge involving many sociocultural factors requires culturally sensitive, interdisciplinary approaches to ensure direct-to-brain innovations are implemented ethically and equitably. This review summarises the state of the science for using neuromodulation to treat opioid use disorder, as well as the available ethical discourse surrounding the expansion of clinical trials and eventual widespread clinical implementation. Additional ethics discussions highlight opportunities for the engineering and clinical evolution of neuromodulation for opioid use disorder trials.

Sacral neuromodulation remote programming in patients with refractory lower urinary tract dysfunction: China's experience during the COVID-19 pandemic.

Objectives: Sacral neuromodulation is an effective, minimally invasive treatment for refractory lower urinary tract dysfunction. However, regular postoperative programming is crucial for the maintenance of the curative effects of electronic sacral stimulator devices. The outbreak of coronavirus disease 2019 (COVID-19) limited the ability of practitioners to perform traditional face-to-face programming of these stimulators. Therefore, this study aimed to evaluate the application of remote programming technology for sacral neuromodulation during the COVID-19 pandemic in China. Materials and methods: We retrospectively collected data including baseline and programming information of all patients with lower urinary tract dysfunction who underwent sacral neuromodulation remote programming in China after the outbreak of COVID-19 (i.e., December 2019). The patients also completed a self-designed telephone questionnaire on the subject. Results: A total of 51 patients from 16 centers were included. They underwent 180 total remote programming visits, and 118, 2, 25, and 54 voltage, current, pulse width, and frequency adjustments, respectively, were performed. Additionally, remote switching on and off was performed 8 times; impedance test, 54 times; and stimulation contact replacement, 25 times. The demand for remote programming was the highest during the first 6 months of sacral neuromodulation (average, 2.39 times per person). In total, 36 out of the 51 patients completed the questionnaire survey. Of these, all indicated that they chose remote programming to minimize unnecessary travel because they had been affected by COVID-19. The questionnaire also showed that remote programming could reduce the number of patient visits to the hospital, save time, reduce financial costs, and would be easy for patients to master. All surveyed patients indicated that they were satisfied with remote programming and were willing to recommend it to other patients. Conclusion: Remote programming for sacral neuromodulation is feasible, effective, safe, and highly recommended by patients with refractory lower urinary tract dysfunction. Remote programming technology has great development and application potential in the post-pandemic era.

Speaker Gender Representation at the North American Neuromodulation Society Annual Meeting (2017-2021): Have We Made Progress in Closing the Gender Gap?

Background: Speaker gender representation at medical conferences is a significant site of gender disparity. Our primary objective was to quantify the proportion of female speakers and compare plenary session opportunities by gender at the North American Neuromodulation Society (NANS) Annual Conference. Methods: Data from the 2017-2021 NANS Annual Conference presentations were abstracted. Primary outcomes included gender composition of speaker slots, gender composition of individual speakers, and comparison of plenary speaker slots by gender. Secondary outcomes included comparisons of session size, age, professional degree, and number of presentations per speaker based on gender. Results: Gender composition of annual speaker slots was (% slots presented by women): 2017:14.6%; 2018:20.5%; 2019:23.5%; 2020:21.0%; 2021:41.4%. Annual gender composition of individual speakers was (% women): 2017:18.7%; 2018:20.6%; 2019:24.6%; 2020:24.9%; 2021:33.8%. Of all speaker slots, the percentage of plenary slots did not differ based on gender, with 11.4% presented by female speakers versus 11.2% presented by male speakers (OR 1.0, 95% CI 0.7-1.5, P=0.893). Compared to male speaker slots, there was an association of lower age (43.9±5.6 vs 50.8±8.9, P<0.001), lower odds of holding a single doctorate degree (OR 0.3, 95% CI 0.2-0.5, P<0.001), and lower odds of holding a dual MD/PhD or DO/PhD degree (OR 0.3, 95% CI 0.1-0.5, P<0.001) in female speaker slots. Compared to male speakers, there was an association of higher number of presentations per female speaker at the 2021 NANS Annual Meeting (2.48±1.60 vs 1.79±1.30, P=0.008). Conclusion: Although the volume of female speaker slots and individual speakers trailed behind their male counterparts, female speaker representation steadily increased at each subsequent annual NANS meeting. We identified no difference in plenary session slots based on gender.

Sinus node dysfunction and atrial fibrillation-Relationships, clinical phenotypes, new mechanisms, and treatment approaches.

Although the anatomical basis of the pathogenesis of sinus node dysfunction (SND) and atrial fibrillation (AF) is located primarily in the left and right atria, increasing evidence suggests a strong correlation between SND and AF, in terms of both clinical presentation and formation mechanisms. However, the exact mechanisms underlying this association are unclear. The relationship between SND and AF may not be causal, but is likely to involve common factors and mechanisms, including ion channel remodeling, gap junction abnormalities, structural remodeling, genetic mutations, neuromodulation abnormalities, the effects of adenosine on cardiomyocytes, oxidative stress, and viral infections. Ion channel remodeling manifests primarily as alterations in the "funny" current (If) and Ca2+ clock associated with cardiomyocyte autoregulation, and gap junction abnormalities are manifested primarily as decreased expression of connexins (Cxs) mediating electrical impulse propagation in cardiomyocytes. Structural remodeling refers primarily to fibrosis and cardiac amyloidosis (CA). Some genetic mutations can also cause arrhythmias, such as SCN5A, HCN4, EMD, and PITX2. The intrinsic cardiac autonomic nervous system (ICANS), a regulator of the heart's physiological functions, triggers arrhythmias.In addition, we discuss arrhythmias caused by viral infections, notably Coronavirus Disease 2019 (COVID-19). Similarly to upstream treatments for atrial cardiomyopathy such as alleviating CA, ganglionated plexus (GP) ablation acts on the common mechanisms between SND and AF, thus achieving a dual therapeutic effect.

Is the post-COVID-19 syndrome a severe impairment of acetylcholine-orchestrated neuromodulation that responds to nicotine administration?

Following a SARS-CoV-2 infection, many individuals suffer from post-COVID-19 syndrome. It makes them unable to proceed with common everyday activities due to weakness, memory lapses, pain, dyspnea and other unspecific physical complaints. Several investigators could demonstrate that the SARS-CoV-2 related spike glycoprotein (SGP) attaches not only to ACE-2 receptors but also shows DNA sections highly affine to nicotinic acetylcholine receptors (nAChRs). The nAChR is the principal structure of cholinergic neuromodulation and is responsible for coordinated neuronal network interaction. Non-intrinsic viral nAChR attachment compromises integrative interneuronal communication substantially. This explains the cognitive, neuromuscular and mood impairment, as well as the vegetative symptoms, characterizing post-COVID-19 syndrome. The agonist ligand nicotine shows an up to 30-fold higher affinity to nACHRs than acetylcholine (ACh). We therefore hypothesize that this molecule could displace the virus from nAChR attachment and pave the way for unimpaired cholinergic signal transmission. Treating several individuals suffering from post-COVID-19 syndrome with a nicotine patch application, we witnessed improvements ranging from immediate and substantial to complete remission in a matter of days.

Transcutaneous auricular vagus nerve stimulation effects on inflammatory markers and clinical evolution of patients with COVID-19: a pilot randomized clinical trial.

OBJECTIVE: To evaluate the effects of transcutaneous auricular vagus nerve stimulation (taVNS) on inflammatory markers and clinical outcomes in patients with COVID-19. METHODS: A randomized blinded pilot study was carried out with 21 individuals hospitalized with COVID-19 who received 14 sessions of active (a-taVNS) or sham taVNS (s-taVNS). The level of interleukin-6 (IL-6), interleukin-10 (IL-10), cortisol, and C-reactive protein (CRP) in plasma and clinical evolution pre- and post-intervention were evaluated. The memory and attention levels were evaluated 14 days after the end of the treatment. RESULTS: After treatment, significant intragroup differences were found in the CRP (p = 0.01), IL-6 (p = 0.01), and cortisol (p = 0.01) levels; however, in the comparison between the groups, only the CRP level was statistically lower for the a-taVNS (p = 0.04). The impression of improvement in memory and attention was greater in the a-taVNS than in the s-taVNS (p = 0.01, p = 0.04, respectively). There was no difference between the other clinical outcomes. CONCLUSIONS: taVNS is a viable and safe intervention in the acute care of patients with COVID-19, which can modulate their inflammatory profile and improve cognitive symptoms. However, improvements in overall clinical outcomes were not detected. Larger sample sizes and longer follow-ups are needed to confirm the anti-inflammatory and clinical effects of taVNS in patients with COVID-19. TRIALS REGISTRY: The Brazilian Registry of Clinical Trials (RBR-399t4g5).

Female LUTS adaptations to COVID era: Lessons learned from the ICS TURNOVER (Transition of fUnctional uRology to New COVID ERa).

Introduction: The COVID-19 pandemic has dramatically affected the Female and Functional Urology (FFU) practice, leading to massive waiting lists, while patients' quality of life remains severely impaired. The aim of the present study is to develop consensual recommendations to guide clinicians on the management of FFU patients. The present paper focuses on female LUTS. Methods: The authors used the Delphi methodology to develop a robust survey questionnaire, covering the principal topics in FFU, based on literature review and expert opinions. Regarding female LUTS, a 98-question survey was distributed among FFU specialists to obtain optimized recommendations, under the auspicious of the International Continence Society (TURNOVER, ICS project). A quantitative analysis of the data was performed, categorizing the mean value from 0-10. Consensus achievement was defined as attaining ≥ 70% agreement. Results: 98 ICS members completed the F-LUTS survey. Recommendations for the diagnosis and management of female LUTS are summarized. Video-consultation should be used for initial assessment, sending questionnaires and bladder diaries in advance to the patient to be filled out before the consultation. However, face-to-face visits are mandatory if POP or continuous incontinence are suspected, and prior to any surgical procedure, regardless of the health alert. Moreover, prescribing medications such as anticholinergics or ß 3 agonists in a telemedicine setting is not considered a safe practice. Follow-up teleconsultations can be used to assess the efficacy and treatment-related adverse events.Urodynamic testing should be only performed if consequences on F-LUTS treatment are expected. The study should be postponed until the pandemic local behaviour flattens.Invasive procedures should be postponed during a high alert. In case surgery is scheduled, outpatient clinics and local anaesthesia should be prioritized. Every patient should be screened for SARS-CoV-2 infection before invasive tests or procedures, following local authorities' guidance. Conclusions: During a pandemic, telemedicine offers a novel way of communication, maintaining medical care while preventing viral transmission. Non-urgent procedures should be postponed until the pandemic curve flattens. Ambulatory procedures under regional or local anaesthesia should be prioritized, aiming to reduce bed occupancy and risk of transmission.

Tremor evaluation using smartphone accelerometry in standardized settings.

Tremor can be highly incapacitating in everyday life and typically fluctuates depending on motor state, medication status as well as external factors. For tremor patients being treated with deep-brain stimulation (DBS), adapting the intensity and pattern of stimulation according the current needs therefore has the potential to generate better symptomatic relief. We here describe a procedure for how patients independently could perform self-tests in their home to generate sensor data for on-line adjustments of DBS parameters. Importantly, the inertia sensor technology needed exists in any standard smartphone, making the procedure widely accessible. Applying this procedure, we have characterized detailed features of tremor patterns displayed by both Parkinson's disease and essential tremor patients and directly compared measured data against both clinical ratings (Fahn-Tolosa-Marin) and finger-attached inertia sensors. Our results suggest that smartphone accelerometry, when used in a standardized testing procedure, can provide tremor descriptors that are sufficiently detailed and reliable to be used for closed-loop control of DBS.

Closed-Loop Systems in Neuromodulation: Electrophysiology and Wearables.

Most currently available neuromodulation techniques for pain work through an open-loop system. The distance between the epidural space and the target of the stimulation in a dynamic body can change because of physiologic conditions. The closed-loop system in spinal cord neuromodulation consists of an integrated system that records real-time electrophysiological activity in the form of evoked compound action potentials and uses it in a feedback mechanism to adjust stimulus output. Wearables represent newly developed technologies that have gained traction in recent years. Their application in pain management is still developing but promising.