Vagus nerve stimulation for focal seizures.

BACKGROUND: This is an updated version of the Cochrane Review published in 2015. Epilepsy is a chronic neurological disorder, characterised by recurring, unprovoked seizures. Vagus nerve stimulation (VNS) is a neuromodulatory treatment that is used as an adjunctive therapy for treating people with drug-resistant epilepsy. VNS consists of chronic, intermittent electrical stimulation of the vagus nerve, delivered by a programmable pulse generator. OBJECTIVES: To evaluate the efficacy and tolerability of VNS when used as add-on treatment for people with drug-resistant focal epilepsy. SEARCH METHODS: For this update, we searched the Cochrane Register of Studies (CRS), and MEDLINE Ovid on 3 March 2022. We imposed no language restrictions. CRS Web includes randomised or quasi-randomised controlled trials from the Specialised Registers of Cochrane Review Groups, including Epilepsy, CENTRAL, PubMed, Embase, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform. SELECTION CRITERIA: We considered parallel or cross-over, randomised, double-blind, controlled trials of VNS as add-on treatment, which compared high- and low-level stimulation (including three different stimulation paradigms: rapid, mild, and slow duty-cycle), and VNS stimulation versus no stimulation, or a different intervention. We considered adults or children with drug-resistant focal seizures who were either not eligible for surgery, or who had failed surgery. DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methods, assessing the following outcomes: 1. 50% or greater reduction in seizure frequency 2. Treatment withdrawal (any reason) 3. Adverse effects 4. Quality of life (QoL) 5. Cognition 6. Mood MAIN RESULTS: We did not identify any new studies for this update, therefore, the conclusions are unchanged. We included the five randomised controlled trials (RCT) from the last update, with a total of 439 participants. The baseline phase ranged from 4 to 12 weeks, and double-blind treatment phases from 12 to 20 weeks. We rated two studies at an overall low risk of bias, and three at an overall unclear risk of bias, due to lack of reported information about study design. Effective blinding of studies of VNS is difficult, due to the frequency of stimulation-related side effects, such as voice alteration. The risk ratio (RR) for 50% or greater reduction in seizure frequency was 1.73 (95% confidence interval (CI) 1.13 to 2.64; 4 RCTs, 373 participants; moderate-certainty evidence), showing that high frequency VNS was over one and a half times more effective than low frequency VNS. The RR for treatment withdrawal was 2.56 (95% CI 0.51 to 12.71; 4 RCTs, 375 participants; low-certainty evidence). Results for the top five reported adverse events were: hoarseness RR 2.17 (99% CI 1.49 to 3.17; 3 RCTs, 330 participants; moderate-certainty evidence); cough RR 1.09 (99% CI 0.74 to 1.62; 3 RCTs, 334 participants; moderate-certainty evidence); dyspnoea RR 2.45 (99% CI 1.07 to 5.60; 3 RCTs, 312 participants; low-certainty evidence); pain RR 1.01 (99% CI 0.60 to 1.68; 2 RCTs; 312 participants; moderate-certainty evidence); paraesthesia 0.78 (99% CI 0.39 to 1.53; 2 RCTs, 312 participants; moderate-certainty evidence). Results from two studies (312 participants) showed that a small number of favourable QOL effects were associated with VNS stimulation, but results were inconclusive between high- and low-level stimulation groups. One study (198 participants) found inconclusive results between high- and low-level stimulation for cognition on all measures used. One study (114 participants) found the majority of participants showed an improvement in mood on the Montgomery-Åsberg Depression Rating Scale compared to baseline, but results between high- and low-level stimulation were inconclusive. We found no important heterogeneity between studies for any of the outcomes. AUTHORS' CONCLUSIONS: VNS for focal seizures appears to be an effective and well-tolerated treatment. Results of the overall efficacy analysis show that high-level stimulation reduced the frequency of seizures better than low-level stimulation. There were very few withdrawals, which suggests that VNS is well tolerated. Adverse effects associated with implantation and stimulation were primarily hoarseness, cough, dyspnoea, pain, paraesthesia, nausea, and headache, with hoarseness and dyspnoea more likely to occur with high-level stimulation than low-level stimulation. However, the evidence for these outcomes is limited, and of moderate to low certainty. Further high-quality research is needed to fully evaluate the efficacy and tolerability of VNS for drug-resistant focal seizures.

A new medication, a new toxidrome - A case report of anticholinergic wipe toxicity due to improper medication use.

We describe a case of a young female who presented to the emergency department with 4 days of progressive myopia, dry mouth, anhidrosis and urinary hesitancy due to overuse of a new topical anticholinergic wipes, glycopyrronium tosylate (GT). In the United States medication misuse accounts for nearly 10% of pediatric emergency visits with 65% of these visits considered to be preventable [1]. Being familiar with new medications and their side effect profiles can prevent unnecessary or harmful interventions.

Transient vocal fold lesion and hoarseness associated with the use of ramucirumab: Case report.

INTRODUCTION: Gastric cancer (GC) is among the leading neoplasms with highest morbidity and mortality in the world. Tumor angiogenesis represents one of important targets of antineoplastic treatment, as it has an important role in cell development and growth. CASE REPORT: Ramucirumab, an IgG1 monoclonal antibody (MoAb), inhibits the angiogenesis pathway by blocking the VEGFR-2 activation. The most common adverse events associated with angiogenic inhibitors are cardiovascular and healing disorders, such as systemic arterial hypertension (HTN), thromboembolism, bleeding, wound healing delay and fistulas. We report a case of vocal fold lesion associated with ramucirumab in a patient with metastatic gastric cancer. The patient presented with transient hoarseness that was related to the exposure to ramucirumab. DISCUSSION: Laryngeal toxicity due to anti-angiogenic agents is rare. Despite the fact that this adverse event is not a life-threatening complication, it can significantly impair quality of life and should be promptly recognized.

Aripiprazole-Induced Hoarseness: A Case Report.

OBJECTIVES: Aripiprazole is an atypical antipsychotic drug that is commonly used in children and adolescents. METHODS: The most common adverse effects of aripiprazole include fatigue, nausea, increased appetite, headache, sedation, and somnolence. RESULTS: To our knowledge, there are no data regarding aripiprazole-induced hoarseness in the existing literature. CONCLUSIONS: We present a case of a preschool boy with attention-deficit/hyperactivity disorder and oppositional defiant disorder who displayed hoarseness after aripiprazole therapy.

[Spacer, Aerosol Therapy through Space and Time]. / Spacer, Aerosoltherapie durch Raum und Zeit.

Aim of the literature review Within this review, results of a literature analysis on the application of spacers with pressurized metered dose inhalers (pMDI) are described and evaluated. Methods Next to an extensive revision on effects of spacers, the impacts of current guidelines and the conditions for product authorisations on the use of spacers are described which result from the interplay of characteristics from dose inhalers with a spacer. Results Spacers are generally useful to avoid coordination problems concerning the actuation of a pMDI at the beginning of an inhalation. Furthermore, in comparison to the pMDI application without a spacer a reduced mouth-throat deposition is applicable to all pMDI spacer combinations. However, some new pMDI release the aerosol in a quality that may not necessarily require a spacer to avoid a high drug deposition in the mouth-throat area as the aerosol quality will not be greatly improved with a spacer. The delivered mass of the active ingredient as well as the aerosol quality released from a spacer vary substantially with the use of different spacers. A change of spacer while using the same dose inhaler can maximally result in a doubling or halving of the quantity of the active ingredient applied. These facts are nowadays considered by the European regulatory agency. Conclusion If a spacer application is intended for pMDIs that were developed and approved after 2009, the correspondent SMP (Summary of Product Characteristics) should at least make one specific recommendation for a spacer that should be based upon relevant in vitro data or additional in vivo data. If a different spacer than the recommended one is used, the effectively applied dose cannot be correctly anticipated. This should be considered when choosing a spacer.

Inhaled Corticosteroids and Voice Problems. What Is New?

BACKGROUND: Voice problems are the most common and most annoying local side effect of inhaled corticosteroids (ICS), affecting not only patients' treatment compliance but also their quality of life. The literature is very poor regarding prevalence, mechanism, prevention, and management of voice problems attributed to ICS use and especially for the new ICS, ciclesonide. Prevalence of dysphonia seems to be less common with the use of ciclesonide and beclomethasone dipropionate. METHOD: We conducted a bibliography review based on recently published data, including data from the recently introduced ICS, ciclesonide, which are lacking in previous reviews. RESULTS: Very little improvement, based on limited number of new papers published during previous years without any direct comparison between available ICS, has been made in our understanding of ICS local side effects. CONCLUSION: Our understanding concerning basic information of ICS effects on voice still remains poor, and further investigation is needed to have a better understanding on epidemiology, predisposing factors, mechanisms, prevention, and treatment of voice problems attributed to ICS.

Laryngeal Side Effects of Tyrosine Kinase Inhibitors.

OBJECTIVES: Tyrosine kinase inhibitors (TKIs) are common targeted drugs, used in the treatment of hematological and solid malignancies. These drugs present a multitude of potential adverse effects. Laryngeal manifestations, including laryngeal edema, secondary to TKIs treatment have not been well studied, despite their potential lethality. METHODS: This cross-sectional study included adult patients (>18 years) treated with TKIs who were followed in a secondary medical center and underwent a voluntary otolaryngological examination, which included laryngeal fiber-optic laryngoscopy (FOL). FOL was independently performed by two senior otolaryngologists, and results were recorded and evaluated by two grading systems, to assess the degree of laryngeal edema. In addition, medical files were reviewed, and data collected included past medical history, signs and symptoms, physical examination, laboratory results, treatment type, and duration. RESULTS: Sixteen patients, aged 68.2 ± 13.6 years, were examined during October 2014 to December 2014. Of them, three (19%) were males. Eleven (68%) patients presented with varying degrees of laryngeal edema. A significant correlation was found between gastroesophageal reflux symptoms and laryngeal edema (P = 0.02). TKI treatment was stopped in one patient, because of symptomatic laryngeal edema, which completely resolved within 2 weeks. CONCLUSIONS: Laryngeal edema was common in our study group. This edema was most often not life threatening. Yet, because of the potential severity of this side effect, we propose a routine FOL examination of patients before commencing TKI treatment and a reevaluation performed during treatment.

Dry mouth as a novel indicator of hoarseness caused by inhalation therapy.

OBJECTIVE: To investigate the influence of dry mouth on the incidence and severity of inhalation therapy-induced hoarseness. METHODS: The volume of saliva secreted without stimulation was measured in patients with asthma or chronic obstructive pulmonary disease (COPD) who also answered a questionnaire on subjective ratings for hoarseness. The relationship between salivary secretion and hoarseness was analyzed by the Pearson correlation and multiple linear regression. The prediction accuracy of salivary secretion for the grade of hoarseness was evaluated using a receiver-operating characteristic (ROC) analysis. RESULTS: A total of 232 patients participated in this study. The subjective rating score of hoarseness was negatively correlated with the volume of saliva secreted (r = -0.273, p < 0.001). A stepwise multiple linear regression analysis revealed that salivary secretion (p < 0.001) and the dose of fluticasone administered (p < 0.05) were significant variables for predicting hoarseness. The ROC analysis for predicting severe hoarseness by salivary secretion showed significant prediction accuracy (AUC = 0.690, 95% CI: 0.614-0.766, p < 0.001) and was higher in patients administered fluticasone (AUC = 0.732, 95% CI: 0.644-0.821, p < 0.001). CONCLUSIONS: Hyposalivation is a significant prediction factor of hoarseness induced by inhaled corticosteroids (ICS). The prediction accuracy was higher in patients administered fluticasone than in those administered another inhalation drug. Although the pharmaceutical efficacy of fluticasone is high, patients with hyposalivation should be prescribed other inhalation drugs.

Absence of gargling affects topical adverse symptoms caused by inhaled corticosteroids in females.

OBJECTIVE: Topical adverse events caused by inhaled corticosteroids (ICS) are suspected to be more common in females. Although gargling or mouth washing after inhalation is recommended as the gold standard for preventing adverse events due to ICS, the preventive effects of this method have not been confirmed in real-world studies. This study aimed to examine the association between gargling or mouth washing and the incidence of topical adverse symptoms in males and females in daily practice. METHODS: We analyzed a subpopulation of participants in the Drug Event Monitoring (DEM) project of the Japan Pharmaceutical Association. An anonymous survey was performed in February 2010, to assess the self-perception of topical adverse symptoms during ICS use by conducting interviews of pharmacists using structured questionnaires. RESULTS: A total of 412 males and 480 females were included. The patients used a dry-powder inhaler (DPI) (71.2%), pressurized meter-dose inhaler (pMDI) with (7.5%) or without (16.6%) a spacer or inhalation solution (4.7%) as the delivery device. Topical adverse symptoms occurring after previous prescriptions were reported by 41 (4.6%) subjects. The common symptoms were hoarseness, stomatitis and dry mouth (1.3%, 1.1% and 1.1%, respectively). In the multiple regression model, the presence of symptoms was found to be significantly associated with the absence of gargling or mouth washing after inhalation [adjusted odds ratio (OR): 3.75, 95% confidence interval (95%CI): 1.33-10.59, p = 0.012]. When stratified by gender, the absence of gargling or mouth washing was identified to be a risk factor in females only (OR: 4.32, 95%CI: 1.11-16.87, p = 0.035) and not in males (OR: 3.26, 95%CI: 0.65-16.33, p = 0.151). Furthermore, the association between the absence of gargling or mouth washing and the incidence of topical adverse symptoms was significant in the patients using DPI (OR: 4.85, 95%CI: 1.66-14.14, p = 0.004), but not in those using the other devices. CONCLUSIONS: In this study, the absence of gargling or mouth washing after ICS use was associated with topical adverse symptoms, especially in females. To achieve good adherence to treatment and improve the quality of life, female patients with asthma should strictly practice the gargling or mouth washing method.

Local adverse effects associated with the use of inhaled corticosteroids in patients with moderate or severe asthma.

OBJECTIVE: To describe and characterize local adverse effects (in the oral cavity, pharynx, and larynx) associated with the use of inhaled corticosteroids (ICSs) in patients with moderate or severe asthma. METHODS: This was a cross-sectional study involving a convenience sample of 200 asthma patients followed in the Department of Pharmaceutical Care of the Bahia State Asthma and Allergic Rhinitis Control Program Referral Center, located in the city of Salvador, Brazil. The patients were ≥ 18 years of age and had been using ICSs regularly for at least 6 months. Local adverse effects (irritation, pain, dry throat, throat clearing, hoarseness, reduced vocal intensity, loss of voice, sensation of thirst, cough during ICS use, altered sense of taste, and presence of oral candidiasis) were assessed using a 30-day recall questionnaire. RESULTS: Of the 200 patients studied, 159 (79.5%) were women. The mean age was 50.7 ± 14.4 years. In this sample, 55 patients (27.5%) were using high doses of ICS, with a median treatment duration of 38 months. Regarding the symptoms, 163 patients (81.5%) reported at least one adverse effect, and 131 (65.5%) had a daily perception of at least one symptom. Vocal and pharyngeal symptoms were identified in 57 (28.5%) and 154 (77.0%) of the patients, respectively. The most commonly reported adverse effects were dry throat, throat clearing, sensation of thirst, and hoarseness. CONCLUSIONS: Self-reported adverse effects related to ICS use were common among the asthma patients evaluated here.

Local adverse effects associated with the use of inhaled corticosteroids in patients with moderate or severe asthma / Eventos adversos locais associados ao uso de corticosteroides inalatorios em pacientes com asma moderada ou grave

OBJECTIVE: To describe and characterize local adverse effects (in the oral cavity, pharynx, and larynx) associated with the use of inhaled corticosteroids (ICSs) in patients with moderate or severe asthma. METHODS: This was a cross-sectional study involving a convenience sample of 200 asthma patients followed in the Department of Pharmaceutical Care of the Bahia State Asthma and Allergic Rhinitis Control Program Referral Center, located in the city of Salvador, Brazil. The patients were ≥ 18 years of age and had been using ICSs regularly for at least 6 months. Local adverse effects (irritation, pain, dry throat, throat clearing, hoarseness, reduced vocal intensity, loss of voice, sensation of thirst, cough during ICS use, altered sense of taste, and presence of oral candidiasis) were assessed using a 30-day recall questionnaire. RESULTS: Of the 200 patients studied, 159 (79.5%) were women. The mean age was 50.7 ± 14.4 years. In this sample, 55 patients (27.5%) were using high doses of ICS, with a median treatment duration of 38 months. Regarding the symptoms, 163 patients (81.5%) reported at least one adverse effect, and 131 (65.5%) had a daily perception of at least one symptom. Vocal and pharyngeal symptoms were identified in 57 (28.5%) and 154 (77.0%) of the patients, respectively. The most commonly reported adverse effects were dry throat, throat clearing, sensation of thirst, and hoarseness. CONCLUSIONS: Self-reported adverse effects ...

OBJETIVO: Descrever e caracterizar os eventos adversos locais na orofaringe e laringe associados ao uso de corticosteroide inalatório (CI) em pacientes com asma moderada ou grave. MÉTODOS: Estudo de corte transversal, com amostra de conveniência composta por 200 pacientes acompanhados no Serviço de Assistência Farmacêutica da Central de Referência do Programa para Controle da Asma na Bahia, em Salvador (BA). Os pacientes tinham ≥ 18 anos e estavam em uso regular de CI por período ≥ 6 meses. Os eventos adversos locais (irritação, dor, garganta seca, pigarro, rouquidão, redução da potência da voz, perda de voz; sensação de sede, tosse durante inalação, alteração do paladar e presença de monilíase oral) foram avaliados por meio de um questionário com período recordatório de 30 dias. RESULTADOS: Dos 200 pacientes estudados, 159 (79,5%) eram mulheres. A média de idade foi de 50,7 ± 14,4 anos. Nesta amostra, 55 pacientes (27,5%) utilizavam altas doses de CI, com mediana de duração de tratamento de 38 meses. Em relação aos sintomas, 163 pacientes (81,5%) reportaram ao menos um evento adverso, e 131 (65,5%) tinham a percepção diária de pelo menos um sintoma. Os sintomas de voz e de faringe foram identificados em 57 (28,5%) e 154 (77,0%) pacientes, respectivamente. Os eventos adversos mais frequentemente relatados foram garganta seca, ...

Regional anesthesia for carotid endarterectomy: a comparison between ropivacaine and levobupivacaine.

BACKGROUND: This study compares ropivacaine and levobupivacaine when administered for cervical plexus block. The authors therefore compared the arterial pressure profile and the incidence of hypotension between drugs. METHODS: Forty-eight patients scheduled for carotid artery surgery (American Society of Anesthesiologists [ASA] 2-3) were randomly assigned to receive levobupivacaine or ropivacaine (24 patients each). Neurological status, arterial pressure profile and control of postoperative pain were the main observed parameters. All patients had severe carotid stenosis (>80%) and/or had suffered transient ischemic attacks (TIAs) or preoperative strokes. The same team performed anesthesia and surgery for carotid endarterectomy; the cervical block was performed according to Moore's technique.Arterial pressure, heart rate and S(a)O(2p) were monitored continuously with particular regard to T0 (baseline), T1 (immediately before carotid clamping), T2 (immediately before declamping) and T3 (at the end of the procedure). Hypotension was defined as the fall of arterial systolic pressure 30% below baseline or less than 100 mmHg. RESULTS: Arterial pressure fell significantly in both groups at T1 with respect to T0 (P<0.0001). Levobupivacaine patients showed higher mean arterial pressure on T0 (112+/-12 mmHg versus 103+/-7 mmHg; P<0.05), thus suggesting a more pronounced vasodilator effect, as confirmed by the larger drop of arterial diastolic pressure (P=0.007). An absolute 6% difference of hypotension-related drug was recorded with levobupivacaine (19%) as compared with ropivacaine (13%) (P=0.28). CONCLUSIONS: Levobupivacaine has a greater vasodilatory effect than ropivacaine. Its higher incidence of hypotension, although not statistically significant, suggests ropivacaine as the drug of choice for cervical plexus block.

Late laryngeal findings in sulfur mustard poisoning.

INTRODUCTION: Sulfur mustard is an alkylating warfare agent and its inhalation results in early and late toxic effects. This agent was used widely against both military and civilian population by Iraqi forces in the Iran-Iraq war (1983-88). The purpose of the study was to describe abnormal laryngeal findings in a group of chemical war injury patients (soldiers) 20 years after an acute exposure to sulfur mustard. METHODS: In this observational case series study, 50 male patients who were suffering from chronic respiratory symptoms and because of exacerbation of these problems, were consecutively selected and clinically examined for dysphonia by a speech-language pathologist, and then underwent fiberoptic laryngobronchoscopy to describe anatomical and functional pathologic findings of the larynx. RESULTS: In objective speech evaluation, different degrees of dysphonia including harshness and hoarseness were observed in 46% of patients. Inflammation was present in supraglottic and subglottic regions of 9 (18%) and 3 (6%) patients, respectively. Hyperfunction of the false vocal cords was observed in 24 (48%) patients. CONCLUSION: Chronic laryngitis was seen in a considerable number of exposed victims nearly 20 years after exposure, in spite of different treatments received.

Ziprasidone-induced tardive laryngeal dystonia: a case report.

Tardive laryngeal dystonia, a rare form of dystonic syndrome, was only reported to be induced by typical antipsychotics. Here, we report one case of ziprasidone-induced tardive laryngeal dystonia in a schizophrenic female patient, who showed dysphonia, hoarseness and dyspnea after taking ziprasidone 120 mg/day for 8 months. These symptoms were significantly improved after discontinuing ziprasidone and increasing the dose of trihexyphenidyl for 1 week. Although atypical antipsychotics are associated with a lower risk of extrapyramidal symptoms, caution should be taken for any tardive dystonic movement when using these medications.

The properties of inhaled corticosteroids: similarities and differences.

Inhaled corticosteroids remain the most important therapy for chronic asthma in both adults and children. As all inhaled corticosteroids act by binding to a common glucocorticoid receptor there is little evidence of any real difference in clinical efficacy between the different inhaled corticosteroids. The main potential differences are in their propensity to cause side effects. Local side effects such as a hoarse voice do occur in a proportion of adults and there is some limited evidence that ciclesonide may cause less local side effects. In adults there is little evidence for clinically important systemic side effects from doses of inhaled steroids below 800 mcg/day (beclomethasone equivalent). Above this dose a proportion of patients may show some adrenocortical suppression, though it is unlikely to be of clinical importance. Data on bone mineral density and fracture rates is discrepant, but an overview would suggest that below 800 mcg/day there is no increase in fracture risk whereas above this dose there might be an increased fracture risk. The properties of ciclesonide would suggest that it has less propensity for systemic side effects, but large long term studies are needed to confirm this. In children using inhaled steroids at above-licensed doses reductions in short-term growth can occur, but there is little evidence for reductions in long-term growth at normal doses. At above-licensed doses, biochemical adrenocortical suppression can occur with some unusual but documented cases of clinical Addisonian crisis. Limited evidence in paediatric age groups would suggest that ciclesonide may have some advantage although it is not as yet licensed in all countries for paediatric use. Data on differences in side effects between normal and asthmatic patients, and between asthmatic patients with near-normal lung function compared to those with impaired lung function, indicate that inhaled corticosteroids (particularly fluticasone) are absorbed more in those with normal lung function; this strongly supports stepping down the inhaled steroid dose when asthma is controlled - as is recommended in asthma guidelines.