Posts Tagged Safety

[Abstract] Efficacy and Safety of High-frequency Repetitive Transcranial Magnetic Stimulation for Post-Stroke Depression:A Systematic Review and Meta-Analysis



To summarize and systematically review the efficacy and safety of high frequency repetitive transcranial magnetic stimulation (HF-rTMS) for depression in stroke patients.

Data Sources

Six databases (Wanfang, CNKI, PubMed, Embase, Cochrane Library, and Web of Science) were searched from inception until November 15, 2018.

Study Selection

Seventeen randomized controlled trials were included for meta-analysis.

Data Extraction

Two independent reviewers selected potentially relevant studies based on the inclusion criteria, extracted data, and evaluated the methodological quality of the eligible trials using the Physiotherapy Evidence Database (PEDro).

Data Synthesis

We calculated the combined effect size (standardized mean difference [SMD] and odds ratio [OR]) for the corresponding effects models. Physiotherapy Evidence Database scores ranged from 7 to 8 points (mean = 7.35). The study results indicated that HF-rTMS had significantly positive effects on depression in stroke patients. The effect sizes of the SMD ranged from small to large (SMD = −1.01; 95% confidence interval [95% CI], −1.36 to −0.66; P < .001; I2 = 85%; n = 1053), and the effect sizes of the OR were large (response rates: 58.43% VS 33.59%; OR = 3.31; 95% CI, 2.25 to 4.88; P < .001; I2 = 0%; n = 529; remission rates: 26.59% VS 12.60%; OR = 2.72; 95% CI, 1.69 to 4.38; P < .001; I2 = 0%; n = 529). In terms of treatment side-effects, the HF-rTMS group was more prone to headache than the control group (OR = 3.53; 95% CI, 1.85 to 8.55; P < .001; I2 = 0%; n = 496).


HF-rTMS is an effective intervention for post-stroke depression, although treatment safety should be further verified via large sample multi-center trials.

via Efficacy and Safety of High-frequency Repetitive Transcranial Magnetic Stimulation for Post-Stroke Depression:A Systematic Review and Meta-Analysis – Archives of Physical Medicine and Rehabilitation

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[Slideshow] Comparing the Safety of Antiepilepsy Drugs in Pregnancy

Comparing the Safety of Antiepilepsy Drugs in Pregnancy

Mar 26, 2018

What are the risks of birth defects and perinatal outcomes for infants exposed to various AEDs in utero?



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[Abstract] Efficacy and safety of NABOTA in post-stroke upper limb spasticity: A phase 3 multicenter, double-blinded, randomized controlled trial


A phase III clinical trial was performed for a novel botulinum toxin A, NABOTA, on post-stroke upper limb spasticity.

NABOTA demonstrated non-inferiority on efficacy and safety compared to onabotulinum toxin A (Botox).

NABOTA may serve as an alternative for treatment of post-stroke upper limb spasticity using botulinum toxin A.


Botulinum toxin A is widely used in the clinics to reduce spasticity and improve upper limb function for post-stroke patients. Efficacy and safety of a new botulinum toxin type A, NABOTA (DWP450) in post-stroke upper limb spasticity was evaluated in comparison with Botox (onabotulinum toxin A). A total of 197 patients with post-stroke upper limb spasticity were included in this study and randomly assigned to NABOTA group (n = 99) or Botox group (n = 98). Wrist flexors with modified Ashworth Scale (MAS) grade 2 or greater, and elbow flexors, thumb flexors and finger flexors with MAS 1 or greater were injected with either drug. The primary outcome was the change of wrist flexor MAS between baseline and 4 weeks post-injection. MAS of each injected muscle, Disability Assessment Scale (DAS), and Caregiver Burden Scale were also assessed at baseline and 4, 8, and 12 weeks after the injection. Global Assessment Scale (GAS) was evaluated on the last visit at 12 weeks. The change of MAS for wrist flexor between baseline and 4 weeks post-injection was − 1.44 ± 0.72 in the NABOTA group and − 1.46 ± 0.77 in the Botox group. The difference of change between both groups was 0.0129 (95% confidence interval − 0.2062–0.2319), within the non-inferiority margin of 0.45. Both groups showed significant improvements regarding MAS of all injected muscles, DAS, and Caregiver Burden Scale at all follow-up periods. There were no significant differences in all secondary outcome measures between the two groups. NABOTA demonstrated non-inferior efficacy and safety for improving upper limb spasticity in stroke patients compared to Botox.


via Efficacy and safety of NABOTA in post-stroke upper limb spasticity: A phase 3 multicenter, double-blinded, randomized controlled trial – ScienceDirect

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[REVIEW] Adverse events of tDCS and tACS: A review – Full Text


  • No serious adverse effects have been reported in experiments using either tDCS or tACS.
  • Persistent adverse effects of tDCS are mainly skin problems; for tACS, none have been reported.
  • Further safety investigations are needed.


Transcranial direct current stimulation (tDCS) and transcranial alternating current stimulation (tACS) have been applied to many research issues because these stimulation techniques can modulate neural activity in the human brain painlessly and non-invasively with weak electrical currents. However, there are no formal safety guidelines for the selection of stimulus parameters in either tDCS or tACS. As a means of gathering the information that is needed to produce safety guidelines, in this article, we summarize the adverse events of tDCS and tACS. In both stimulation techniques, most adverse effects are mild and disappear soon after stimulation. Nevertheless, several papers have reported that, in tDCS, some adverse events persist even after stimulation. The persistent events consist of skin lesions similar to burns, which can arise even in healthy subjects, and mania or hypomania in patients with depression. Recently, one paper reported a pediatric patient presenting with seizure after tDCS, although the causal relationship between stimulation and seizure is not clear. As this seizure is the only serious adverse events yet reported in connection with tDCS, tDCS is considered safe. In tACS, meanwhile, no persistent adverse events have been reported, but considerably fewer reports are available on the safety of tACS than on the safety of tDCS. Therefore, to establish the safety of tDCS and tACS, we need to scan the literature continuously for information on the adverse events of both stimulation techniques. Further safety investigations are also required.

1. Introduction

Since the first reports of transcranial direct current stimulation (tDCS) by Priori et al. (1998)) and Nitsche and Paulus, 2000, Nitsche and Paulus, 2001), tDCS has been applied to many research issues because it can modulate the neural networks in the human brain painlessly and non-invasively (Priori et al., 1998, Nitsche and Paulus, 2000, Nitsche and Paulus, 2001). In other words, tDCS can induce neural plasticity (Ugawa, 2012). Most of its adverse effects are mild and disappear soon after stimulation, but several papers have reported that some adverse effects, most commonly skin problems, can persist even after stimulation. Recently, since the invention of transcranial alternating current stimulation (tACS) by Antal et al. (2008)), tACS has also been applied in research for the modulation of neural activity through the entrainment on brain oscillations (Antal et al., 2008, Antal and Herrmann, 2016). As in tDCS, the adverse effects of tACS are mild and disappear just after stimulation. Yet there have been far fewer papers on safety issues or adverse events of tACS as compared to tDCS. To date, there are no formal safety guidelines for the selection of stimulus parameters in either tDCS or tACS (Fertonani et al., 2015). Therefore, we aim to summarize the adverse events of tDCS and tACS in this review. At present, the safety and ethical issues of both stimulation techniques should be considered by each institution due to the lack of certainty about their risks. This review may provide some useful information for these considerations. In addition, this review is expected to be useful for the establishment of safety guidelines in the near future.

Continue —> Adverse events of tDCS and tACS: A review – Clinical Neurophysiology Practice

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[WEB SITE] Researchers Are Developing a Mobile App to Assist Post-TBI Patients

A decision support mobile app to help facilitate safety and independent living among TBI patients after returning home from a treatment facility is being developed in collaboration between researchers from Alabama-based Shepherd Center and ChartAssist LLC.

To assist with decision-making, the mobile app will be engineered to help improve the assessment of functional mobility, household activities, sleep, and safety risk.

Such decisions include making differential diagnostic assessments, selecting the most appropriate home- and community-based services and supports, measuring progress, and updating healthcare and supervision needs, according to the researchers, in a media release from Shepherd Center.

The app will also feature the ability to provide multidisciplinary treatment recommendations for TBI patients, as well as to set goals and track outcomes.

“I am thankful to have the opportunity to work with Shepherd Center and Dr Ron Seel, director of brain injury research, to help people with TBI and their families,” says Daniel Joye, president of ChartAssist, in the release. “The need for a decision support app is clear, and our company’s work on multidisciplinary rehabilitation in the mental health community is a great fit for helping people with brain injuries, their families and rehabilitation professionals.”

“I was quickly impressed by the innovative software development work that ChartAssist has done in the mental health community, “ states Ron Seel, PhD, the O. Wayne Rollins Director of Brain Injury Research at Shepherd Center, per the release.

“The software that ChartAssist has developed to facilitate person-centered, multidisciplinary rehabilitation assessment and treatment has broad applicability to helping people with brain injuries, who share many of the same chronic cognitive, behavioral, physical and health conditions experienced by people with mental health disabilities. Leveraging this work to develop secure, user-friendly, evidence-based decision support applications is a natural fit and could greatly improve people’s lives.”

Grants from the National Institute on Disability, Independent Living and Rehabilitation Research, as well as the Shepherd Center Foundation, provided the seed money to develop the app.

[Source: Shepherd Center]

Source: Researchers Are Developing a Mobile App to Assist Post-TBI Patients – Rehab Managment

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[ARTICLE] High doses of incobotulinumtoxinA for the treatment of post-stroke spasticity: are they safe and effective? – Full Text 

1. Introduction

Botulinum toxin type A (BoNT-A) represents the gold standard therapy for focal spasticity and related disorders also in acquired brain injury including stroke. Since 1989, the effectiveness of BoNT-A in reducing poststroke spasticity showed reversibility and low prevalence of complications [1], obtaining the approval of U.S. Food and Drug Administration for upper limb spasticity after stroke in 2010. In the following years, many studies have been published demonstrating its safety and effectiveness [2,3]. However, the role of BoNT-A in the management of poststroke spasticity has been modified, changing from muscle chemodenervation (nerve block) to become an useful tool for improving limb posture, applying splint, consenting hygiene, standing, and walking in patients with spastic equino-varus foot deformities with also improvement joint range of motion and muscle extensibility or reduction of spasticity-related pain.
The correct evaluation of the patient to be injected is necessary to increase the efficacy of BoNT-A considering that there is a high response for improving passive function, but controversy also exists about the improvement in motor function relative to the improvement of spasticity. There are proposals on dosages, injection techniques, patient selection, and outcome measures, but a consensus about the employment of adjunctive therapies after the BoNT-A injection, considered necessary to increase the effect on spasticity reduction, has not been reached, considering the time to start, the duration of adjunctive therapies, and the type of rehabilitation procedures [4]. So, at present, the injection sites, the choice of muscles, the dosage, the dilution, and the rehabilitation programs after BoNT-A treatment are often identified by injector’s decision-making without specialized training.
BoNT-A has clearly been recommended as first-line treatment for focal spasticity by several European consensus statements and the American Academy of Neurology [4,5] and current guidelines suggested the employment of a dose up to 600 units (U) of onabotulinumtoxinA (Botox®, Allergan, Inc., Irvine, CA, USA) and incobotulinumtoxinA (Xeomin®, Merz Pharmaceuticals GmbH, Frankfurt, Germany) or up to 1500 U of abobotulinumtoxinA (Dysport®, Ipsen, Slough, UK/Galderma, Paris, France) per injection session to treat spasticity after stroke [5]. However, in recent years, higher doses have been used, especially in case of upper and lower limb severe spasticity considering the low prevalence of complications and the reversibility of the BoNT-A [6,7]. The possibility to employ high doses is strictly related to the precision of the injection. A correct muscle identification with instrumental guide (i.e. electrical stimulation or ultrasonography) may reduce the spread of the toxins to the nearby tissues and the risk of adverse effects.

Continue —> High doses of incobotulinumtoxinA for the treatment of post-stroke spasticity: are they safe and effective? – Expert Opinion on Drug Metabolism & Toxicology –

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[Abstract] Safety of repetitive transcranial magnetic stimulation in patients with epilepsy: A systematic review – Epilepsy & Behavior


We reviewed the crude risk of seizures and other adverse events of rTMS in patients with epilepsy.

A crude per-subject risk of 2.9% (95% CI: 1.3–4.5) was estimated for seizures occurring during or shortly after.

The safety of rTMS applied to patients with epilepsy appears to be the same as in other conditions.


Approximately one-third of patients with epilepsy remain with pharmacologically intractable seizures. An emerging therapeutic modality for seizure suppression is repetitive transcranial magnetic stimulation (rTMS). Despite being considered a safe technique, rTMS carries the risk of inducing seizures, among other milder adverse events, and thus, its safety in the population with epilepsy should be continuously assessed.

We performed an updated systematic review on the safety and tolerability of rTMS in patients with epilepsy, similar to a previous report published in 2007 (Bae EH, Schrader LM, Machii K, Alonso-Alonso M, Riviello JJ, Pascual-Leone A, Rotenberg A. Safety and tolerability of repetitive transcranial magnetic stimulation in patients with epilepsy: a review of the literature. Epilepsy Behav. 2007; 10 (4): 521–8), and estimated the risk of seizures and other adverse events during or shortly after rTMS application.

We searched the literature for reports of rTMS being applied on patients with epilepsy, with no time or language restrictions, and obtained studies published from January 1990 to August 2015. A total of 46 publications were identified, of which 16 were new studies published after the previous safety review of 2007.

We noted the total number of subjects with epilepsy undergoing rTMS, medication usage, incidence of adverse events, and rTMS protocol parameters: frequency, intensity, total number of stimuli, train duration, intertrain intervals, coil type, and stimulation site.

Our main data analysis included separate calculations for crude per subject risk of seizure and other adverse events, as well as risk per 1000 stimuli. We also performed an exploratory, secondary analysis on the risk of seizure and other adverse events according to the type of coil used (figure-of-8 or circular), stimulation frequency (≤1 Hz or >1 Hz), pulse intensity in terms of motor threshold (<100% or ≥100%), and number of stimuli per session (<500 or ≥ 500).

Presence or absence of adverse events was reported in 40 studies (n = 426 subjects). A total of 78 (18.3%) subjects reported adverse events, of which 85% were mild. Headache or dizziness was the most common one, occurring in 8.9%. We found a crude per subject seizure risk of 2.9% (95% CI: 1.3–4.5), given that 12 subjects reported seizures out of 410 subjects included in the analysis after data of patients with epilepsia partialis continua or status epilepticus were excluded from the estimate.

Only one of the reported seizures was considered atypical in terms of the clinical characteristics of the patients’ baseline seizures. The atypical seizure happened during high-frequency rTMS with maximum stimulator output for speech arrest, clinically arising from the region of stimulation. Although we estimated a larger crude per subject seizure risk compared with the previous safety review, the corresponding confidence intervals contained both risks. Furthermore, the exclusive case of atypical seizure was the same as reported in the previous report. We conclude that the risk of seizure induction in patients with epilepsy undergoing rTMS is small and that the risk of other adverse events is similar to that of rTMS applied to other conditions and to healthy subjects.

Our results should be interpreted with caution, given the need for adjusted analysis controlling for potential confounders, such as baseline seizure frequency. The similarity between the safety profiles of rTMS applied to the population with epilepsy and to individuals without epilepsy supports further investigation of rTMS as a therapy for seizure suppression.

Source: Safety of repetitive transcranial magnetic stimulation in patients with epilepsy: A systematic review – Epilepsy & Behavior

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[ARTICLE] Exercise and rehabilitation delivered through exergames in older adults: An integrative review of technologies, safety and efficacy


  • This study focused on technologies, safety and efficacy of exergames for older adults
  • Exergames show good potential as an exercise or rehabilitation tool for older adults
  • Based on the review, recommendations for practice and further research are provided
  • Exergames need to be personalized, safe and address multiple physical functions
  • Future studies should include longer follow-up, social aspects and game adherence


Background: There has been a rapid increase in research on the use of virtual reality (VR) and gaming technology as a complementary tool in exercise and rehabilitation in the elderly population. Although a few recent studies have evaluated their efficacy, there is currently no in-depth description and discussion of different game technologies, physical functions targeted, and safety issues related to older adults playing exergames.

Objectives: This integrative review provides an overview of the technologies and games used, progression, safety measurements and associated adverse events, adherence to exergaming, outcome measures used, and their effect on physical function. Methods: We undertook systematic searches of SCOPUS and PubMed databases. Key search terms included “game”, “exercise”, and “aged”, and were adapted to each database. To be included, studies had to involve older adults aged 65 years or above, have a pre-post training or intervention design, include ICT-implemented games with weight-bearing exercises, and have outcome measures that included physical activity variables and/or clinical tests of physical function.

Results: Sixty studies fulfilled the inclusion criteria. The studies had a broad range of aims and intervention designs and mostly focused on community-dwelling healthy older adults. The majority of the studies used commercially available gaming technologies that targeted a number of different physical functions. Most studies reported that they had used some form of safety measure during intervention. None of the studies reported serious adverse events. However, only 21 studies (35%) reported on whether adverse events occurred. Twenty-four studies reported on adherence, but only seven studies (12%) compared adherence to exergaming with other forms of exercise. Clinical measures of balance were the most frequently used outcome measures. PEDro scores indicated that most studies had several methodological problems, with only 4 studies fulfilling 6 or more criteria out of 10. Several studies found positive effects of exergaming on balance and gait, while none reported negative effects.

Conclusion: Exergames show promise as an intervention to improve physical function in older adults, with few reported adverse events. As there is large variability between studies in terms of intervention protocols and outcome measures, as well as several methodological limitations, recommendations for both practice and further research are provided in order to successfully establish exergames as an exercise and rehabilitation tool for older adults.

Source: Exercise and rehabilitation delivered through exergames in older adults: An integrative review of technologies, safety and efficacy

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[ARTICLE] Transcranial magnetic stimulation: A potential new treatment for depression associated with traumatic brain injury


Background: Each year, more than 1.7 million Americans suffer a traumatic brain injury (TBI) and the lifetime prevalence of major depressive disorder following TBI is between 25–50%. There are no validated established strategies to treat TBI depression. Repetitive transcranial magnetic stimulation (rTMS) is a novel putative treatment option for post-TBI depression, which, compared with standard pharmacological agents, may provide a more targeted treatment with fewer side-effects. However, TBI is associated with an increased risk of both early and late spontaneous seizures, a significant consideration in evaluating rTMS as a potential treatment for TBI depression. Whilst the risk of seizure from rTMS is low, underlying neuropathology may somewhat increase that risk.

Review: This review focuses on the safety aspects of rTMS in TBI patients. The authors review why low frequency rTMS might be less likely to trigger a seizure than high frequency rTMS and propose low frequency rTMS as a safer option in TBI patients. Because there is little data on the safety of rTMS in TBI, the authors also review the safety of rTMS in patients with other brain pathology.

Conclusion: It is concluded that pilot safety and tolerability studies should be first conducted in persons with TBI and neuropsychiatric comorbidities. These results could be used to help design larger randomized controlled trials.

via Transcranial magnetic stimulation: A potential new treatment for depression associated with traumatic brain injury, Brain Injury, Informa Healthcare.

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[ARTICLE] What Do We Really Know About the Safety of Tai Chi?:

…TC is unlikely to result in serious AEs, but it may be associated with minor musculoskeletal aches and pains. However, poor and inconsistent reporting of AEs greatly limits the conclusions that can be drawn regarding the safety of TC…

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