Post-stroke spasticity: follow-up and functional implications of chronic long-term treatment with botulinum toxin.

BACKGROUND: Around 40% of stroke survivor develop spasticity. Plantar flexors (PF) muscles are often affected, with severe functional impairment. The treatment of choice is botulinum toxin type A (BoNT-A) combined with adjuvant treatments. The temporary pharmacological effect implies periodic reassessment and reinjection. These long-term chronic programs require monitoring the functional impact of each cycle and the clinical evolution in relation to aging and repeated interventions. AIM: Evaluating changes of functional level in patients with post-stroke spasticity treated with BoNT-A by assessing the long-term maintenance of the therapeutic efficacy. DESIGN: Retrospective longitudinal observational study. SETTING: Outpatients. POPULATION: Chronic stroke survivors undergoing BoNT-A treatment and subsequent intensive rehabilitation (10 sessions in a day-hospital regime). METHODS: Medical records of the enrolled patients were consulted. The primary endpoint was the change in PF spasticity by at least 1 point on the Modified Ashworth Scale (MAS) at each cycle. Secondary endpoints were the assessment of possible trends in gait parameters (Six Minute Walking Test [6MWT]; Timed Up and Go [TUG], and 10 Meters Walking Test [10mWT]) pre- and post-injection and at each cycle. RESULTS: Thirty-six patients were enrolled. A reduction of at least one MAS point for PF was recorded after each cycle in all subjects. A time-dependent reduction in the proportion of patients reporting an improvement higher than the minimal clinically important difference (MCID) in 6MWT and 10mWT was observed. In the case of TUG, this data kept stable at all cycles. A one-point increase in the basal functional ambulation classification (FAC) score resulted in a reduction in the probability of having a TUG improvement greater than the MCID. The opposite correlation was found for 6MWT and 10mWT. CONCLUSIONS: With the proposed treatment, the clinical significance TUG improvement remains constant throughout repeated cycles and the proportion of patients with improvement in 6MWT and 10mWT tends to decline over time. The predictive value of basal FAC on the functional variables expected improvement may provide a potential treatment targeting tool. CLINICAL REHABILITATION IMPACT: These results may deliver prognostic indication allowing an optimized integration of different post-BoNT-A rehabilitation approaches, agreeing with current evidence. Adequate monitoring and treatment protocols are crucial for the stability of functional level and may prevent excessive fluctuations.

The Role of Botulinum Toxin Type-A in Spasticity: Research Trends from a Bibliometric Analysis.

Botulinum toxin type-A (BoNT-A) has emerged as a key therapeutic agent for the management of spasticity. This paper presents a comprehensive bibliometric and visual analysis of research concerning BoNT-A treatment of spasticity to elucidate current trends and future directions in this research area. A search was conducted in the Web of Science database for articles focused on the use of BoNT-A in spasticity published between 2000 and 2022. We extracted various metrics, including counts of publications and contributions from different countries, institutions, authors, and journals. Analytical methods in CiteSpace were employed for the examination of co-citations, collaborations, and the co-occurrence of keywords. Our search yielded 1489 publications. Analysis revealed a consistent annual increase in research output. The United States, United Kingdom, and Italy were the leading contributors. The top institution in this research was Assistance Publique Hopitaux, Paris. The journal containing the highest number of relevant publications was Toxins. Key frequently occurring keywords were 'stroke', 'cerebral palsy', 'adult spasticity', and 'upper extremity'. This study identified 12 clusters of keywords and 15 clusters of co-cited references, indicating the main focus areas and emerging themes in this field. This study comprehensively analyzed and summarized trends in BoNT-A research in the field of spasticity over the past 22 years.

May Spasticity-Related Unpleasant Sensations Interfere with Daily Activities in People with Stroke and Traumatic Brain Injury? Secondary Analysis from the CORTOX Study.

Background/Objectives: This study examined the impact of spasticity-related unpleasant sensations (pain, heaviness, stiffness) on various domains of the International Classification of Functioning, Disability, and Health (ICF) and psychosocial well-being in individuals affected by stroke or traumatic brain injury (TBI). The primary aim is to explore how these sensations affect daily activities, participation, and overall quality of life, guided by the comprehensive framework of the ICF. Methods: Utilizing a secondary analysis of data from a cohort undergoing Botulinum toxin type-A treatment for spasticity post-stroke or TBI, we developed and administered an ad-hoc questionnaire focusing on ICF domains such as body function, activities and participation, and psychosocial aspects such as mood, relationship, social life, motivation, and sleep quality. Spearman rho correlation was applied to assess the relationship between unpleasant sensations and functional as well as psychosocial outcomes among 151 participants. Results: This study identified significant correlations between the severity of unpleasant sensations and limitations in daily functioning, particularly in activities of daily living and mobility. Furthermore, an impactful association was identified between increased unpleasant sensations and deterioration in psychosocial well-being, notably in mood and sleep quality. Conclusions: These findings advocate for a person-centered approach in spasticity management, emphasizing the integration of sensory impairment strategies into rehabilitation to enhance functional outcomes and quality of life. Such an approach aims to improve functional outcomes and enhance the quality of life for individuals experiencing spasticity post-stroke or TBI. Future directions include targeted interventions to alleviate these sensations, support better rehabilitation results and improve patient experiences.

Anatomical landmarks for ultrasound-guided rectus femoris diagnostic nerve block in post-stroke spasticity.

Introduction/Purpose: To determine the location of the rectus femoris (RF) motor branch nerve, as well as its coordinates with reference to anatomical and ultrasound landmarks. Methods: Thirty chronic stroke patients with stiff knee gait (SKG) and RF hyperactivity were included. The motor nerve branch to the RF muscle was identified medially to the vertical line from anterior superior iliac spine and the midpoint of the superior margin of the patella (line AP) and vertically to the horizontal line from the femoral pulse and its intersection point with the line AP (line F). The point of the motor branch (M) was located with ultrasound, and nerve depth and subcutaneous tissue thickness (ST) were calculated. Results: The coordinates of the motor branch to the RF were 2.82 (0.47) cm medially to the line AP and 4.61 (0.83) cm vertically to the line F. Nerve depth and subcutaneous tissue thickness were 2.71 (0.62) cm and 1.12 (0.75) cm, respectively. Conclusion: The use of specific coordinates may increase clinicians' confidence when performing RF motor nerve block. This could lead to better decision-making when assessing SKG in chronic stroke patients.

Integrated Thermal Rehabilitation Care: An Intervention Study.

BACKGROUND: The aim of this study was to evaluate the effects of integrated thermal rehabilitation care (ITRC) on postural balance and health-related quality of life in subjects with basic autonomy. MATERIALS AND METHODS: From June to December 2021, a total of 50 individuals with six points on the Katz Index of Independence in Activities of Daily Living (ADL) and a mean age of 66 (DS ± 12), comprising 27 (54%) males and 23 (46%) females, were selected. This study was carried out at the Thermal Medical Center of Castelnuovo della Daunia (Foggia, Italy), which operates within the National Health Service. The outcome measures were baropodometry (static exam, dynamic exam, and stabilometric exam), a biometric evaluation system, and the EuroQol 5-Dimension (EQ-5D-5L). RESULTS: Statistical analysis of the data showed how balance affected postural control and how ITRC was able to reduce the body's imbalance and improve quality of life. The vertical angles in frontal projection displayed an increment in the values (head/shoulder, p = 0.009; head/pelvis, p = 0.001; right hip/knee, p = 0.01; right hip/ankle, p = 0.008). In a dynamic analysis, the podalic weight percentage was shown to have a reduction in imbalance on both sides (left side, p = 0.01; right side, p = 0. 01). EQ-5D-5L showed a statistically significant improvement in quality of life and perception of quality of life. Indeed, the health status score improved in all items and in the total rate of the EQ index. In all subjects, walking motility (p = 0.005), self-care (p = 0.002), and habitual activity (p = 0.002) showed statistically significant increments in their values. Pain/discomfort (p = 0.001) and anxiety (p = 0.006) were also reduced. In addition, there was a statistically significant increment in the Visual Analogue Scale (VAS) score (p = 0.001) for life perception. CONCLUSIONS: The ITRC approach showed how small adjustments and postural rebalancing led to a significant improvement in quality of life. ITRC can be considered an effective treatment with good tolerability for a variety of musculoskeletal disorders.

Rehabilitation interventions for glioma patients: a mini-review.

Glioma is a group of tumors that originate from glial cells within the central nervous system and comprise 27% of all tumors and 80% of malignant tumors. With remarkable progress in surgical practices, chemotherapy, and radiation therapy, patients with glioma are experiencing greater survival times, which means they need more rehabilitative care. In fact, people with this condition may experience a variety of symptoms that can affect their functions and drastically reduce their quality of life. In fact, patients suffering from glioma has a distinctive symptom complex highlighting the requirement for customized care. Growing evidence shows that rehabilitation therapy can improve the functional prognosis and quality of life of glioma patients. However, there is limited evidence of the success of rehabilitation protocols designed specifically for individuals with glioma. It is essential to determine the most comprehensive rehabilitation programs as well as the sufficient resources, dosage, and duration. The goal of this mini-review was to classify and map rehabilitation interventions used to treat multiple disabling sequalae in individuals affected by glioma. We aim to provide a comprehensive overview of the rehabilitation protocols used for this population, so that clinicians have a guide to support treatment and an inspiration for further research. This document is intended to be a reference point for professionals involved in the management of adult patients with gliomas. Further exploration is needed to form improved care models for recognizing and addressing functional restrictions in this population.

Sensor-Based Rehabilitation in Neurological Diseases: A Bibliometric Analysis of Research Trends.

BACKGROUND: As the field of sensor-based rehabilitation continues to expand, it is important to gain a comprehensive understanding of its current research landscape. This study aimed to conduct a bibliometric analysis to identify the most influential authors, institutions, journals, and research areas in this field. METHODS: A search of the Web of Science Core Collection was performed using keywords related to sensor-based rehabilitation in neurological diseases. The search results were analyzed with CiteSpace software using bibliometric techniques, including co-authorship analysis, citation analysis, and keyword co-occurrence analysis. RESULTS: Between 2002 and 2022, 1103 papers were published on the topic, with slow growth from 2002 to 2017, followed by a rapid increase from 2018 to 2022. The United States was the most active country, while the Swiss Federal Institute of Technology had the highest number of publications among institutions. Sensors published the most papers. The top keywords included rehabilitation, stroke, and recovery. The clusters of keywords comprised machine learning, specific neurological conditions, and sensor-based rehabilitation technologies. CONCLUSIONS: This study provides a comprehensive overview of the current state of sensor-based rehabilitation research in neurological diseases, highlighting the most influential authors, journals, and research themes. The findings can help researchers and practitioners to identify emerging trends and opportunities for collaboration and can inform the development of future research directions in this field.

Clinical efficacy of botulinum toxin type A in patients with traumatic brain injury, spinal cord injury, or multiple sclerosis: An observational longitudinal study.

Botulinum toxin type A (BoNT-A) is the treatment of choice for focal spasticity, with a concomitant effect on pain reduction and improvement of quality of life (QoL). Current evidence of its efficacy is based mainly on post stroke spasticity. This study aims to clarify the role of BoNT-A in the context of non-stroke spasticity (NSS). We enrolled 86 patients affected by multiple sclerosis, spinal cord injury, and traumatic brain injury with clinical indication to perform BoNT-A treatment. Subjects were evaluated before injection and after 1, 3, and 6 months. At every visit, spasticity severity using the modified Ashworth scale, pain using the numeric rating scale, QoL using the Euro Qol Group EQ-5D-5L, and the perceived treatment effect using the Global Assessment of Efficacy scale were recorded. In our population BoNT-A demonstrated to have a significant effect in improving all the outcome variables, with different effect persistence over time in relation to the diagnosis and the number of treated sites. Our results support BoNT-A as a modifier of the disability condition and suggest its implementation in the treatment of NSS, delivering a possible starting point to generate diagnosis-specific follow-up programs. Clinical trial identifier: NCT04673240.

Balance Rehabilitation through Robot-Assisted Gait Training in Post-Stroke Patients: A Systematic Review and Meta-Analysis.

BACKGROUND: Balance impairment is a common disability in post-stroke survivors, leading to reduced mobility and increased fall risk. Robotic gait training (RAGT) is largely used, along with traditional training. There is, however, no strong evidence about RAGT superiority, especially on balance. This study aims to determine RAGT efficacy on balance of post-stroke survivors. METHODS: PubMed, Cochrane Library, and PeDRO databases were investigated. Randomized clinical trials evaluating RAGT efficacy on post-stroke survivor balance with Berg Balance Scale (BBS) or Timed Up and Go test (TUG) were searched. Meta-regression analyses were performed, considering weekly sessions, single-session duration, and robotic device used. RESULTS: A total of 18 trials have been included. BBS pre-post treatment mean difference is higher in RAGT-treated patients, with a pMD of 2.17 (95% CI 0.79; 3.55). TUG pre-post mean difference is in favor of RAGT, but not statistically, with a pMD of -0.62 (95%CI - 3.66; 2.43). Meta-regression analyses showed no relevant association, except for TUG and treatment duration (ß = -1.019, 95% CI - 1.827; -0.210, p-value = 0.0135). CONCLUSIONS: RAGT efficacy is equal to traditional therapy, while the combination of the two seems to lead to better outcomes than each individually performed. Robot-assisted balance training should be the focus of experimentation in the following years, given the great results in the first available trials. Given the massive heterogeneity of included patients, trials with more strict inclusion criteria (especially time from stroke) must be performed to finally define if and when RAGT is superior to traditional therapy.

Sensor based assessment of turning during instrumented Timed Up and Go Test for quantifying mobility in chronic stroke patients.

BACKGROUND: Turning may be particularly challenging for stroke patients leading to decreased mobility and increased functional restriction. Timed up and go instrumentation using a simple technology in the clinical context could allow for the collection of both traditional and potentially more discriminatory variables in turning ability. AIM: Determine whether the speed turning metrics obtained by a single inertial sensor are suitable for differentiating between stroke patients with varying levels of mobility and disability. DESIGN: Cross-sectional study. SETTING: Outpatients setting. POPULATION: Chronic stroke patients. METHODS: A total of 48 chronic stroke patients and 23 healthy controls were included. Stroke patients were divided in two groups based on the total iTUG score: an impaired mobility (> 20 seconds) and an available mobility (<20 seconds) group. All subjects performed an instrumented Timed Up and Go (iTUG) wearing a single IMU sensor on the lower back. Time of subcomponents of the timed up and go test and kinematic parameters of turning were quantified. Other clinical outcomes were: 10 meters walk test, Functional Ambulation Categories Scale (FAC), the Rivermead Mobility Index (RMI), Modified Rankin Scale and the Saltin-Grimby Physical Activity Level Scale (SGPALS). RESULTS: There were significant differences (P<0.01) in iTUG phases and turning speeds among groups. Low to strong significant correlations were found between measures derived from the turning speeds and clinical measures. The area under the curve (AUC) of Receiver Operating Characteristic (ROC) turning speeds was demonstrated to be able to discriminate (AUC: 0.742-0.912) from available to impaired stroke patients. CONCLUSIONS: This study provides evidence that turning speeds during timed up and go test are accurate measures of mobility and capable of discriminating stroke patients with impaired mobility from those with normal mobility. CLINICAL REHABILITATION IMPACT: The turning metrics are related to impairment and mobility in chronic stroke patients; hence they are important to include during clinical evaluation and may assist in creating a customized strategy, assess potential treatments, and effectively organize recovery.

Nicotine-Free E-Cigarettes Might Promote Tobacco Smoking Reduction Better Than Nicotine Delivery Devices: Results of a Double-Blind Randomized Controlled Trial at 1 Year.

The purpose of the present study was to determine whether the use of e-cigarettes to aid in quitting contributed to the increase in the pulmonary health of chronic smokers. The efficacy of e-cigarettes to support a successful smoking cessation attempt was also investigated. A total of 210 smokers (78 women) were enrolled in a screening program for the early detection of lung cancer and distributed in three arms: nicotine e-cigarette plus support, nicotine-free e-cigarette plus support, and support. Results showed that participants in the nicotine e-cigarette arm had a significant and fast decrease in daily cigarettes, but that later they resume smoking more than the other two groups. Conversely, participants in the other two arms showed similar daily consumption at the two evaluation points. Among abstinent participants, only 12.5% reported cough, while 48% of current smokers had pulmonary symptoms. Our study suggests that, in the long run, the use of a nicotine-free liquid may favor reducing smoking and could be considered a good option in a clinical setting.

Reasons and Determinants of BoNT-A Treatment Discontinuation in Patients Living with Spasticity: A 10-Year Retrospective Analysis.

BACKGROUND: The present study aimed to evaluate the reasons and determinants of BoNT-A discontinuation in patients with stroke, multiple sclerosis, spinal cord injury, and traumatic brain injury. METHODS: It is a retrospective study of 56 discontinuer patients treated with botulinum toxin between January 2011 and December 2021. Discontinuation rates and their predictors were estimated using Kaplan-Meier, Log rank test, and Cox's regression method of analyses. RESULTS: The mean age was 56.54 years, 53.57% were affected by post-stroke spasticity, 17.86% by spinal cord injury, 12.5% and 16.07% by traumatic brain injury and multiple sclerosis, respectively. The median discontinuation time was 5 months. The main reason for discontinuation were logistic problems (37%) and orthopedic surgeries or intrathecal baclofen (27%). Discontinuers were more likely to have severe spasticity (R = 1.785), have no pain (HR = 1.320), no access to rehabilitation services (HR = 1.402), and have cognitive impairment (HR = 1.403). CONCLUSIONS: The main reasons for discontinuation are related to logistic issues (due to distance or the absence of an adequate caregiver) and surgical interventions for spasticity, including intrathecal baclofen. It is crucial to identify possible predictors of discontinuation to improve the effectiveness of a multidisciplinary management. The study confirms the crucial role of rehabilitation and caregivers in achieving better long-term outcomes.

Ultrasonographic Evaluation of Three Approaches for Botulinum Toxin Injection into Tibialis Posterior Muscle in Chronic Stroke Patients with Equinovarus Foot: An Observational Study.

Spastic equinovarus (SEV) foot deformity is commonly observed in patients with post-stroke spasticity. Tibialis posterior (TP) is a common target for botulinum toxin type-A (BoNT-A) injection, as a first-line treatment in non-fixed SEV deformity. For this deep muscle, ultrasonographic guidance is crucial to achieving maximum accuracy for the BoNT-A injection. In current clinical practice, there are three approaches to target the TP: an anterior, a posteromedial, and a posterior. To date, previous studies have failed to identify the best approach for needle insertion into TP. To explore the ultrasonographic characteristics of these approaches, we investigated affected and unaffected legs of 25 stroke patients with SEV treated with BoNT-A. We evaluated the qualitative (echo intensity) and quantitative (muscle depth, muscle thickness, overlying muscle, subcutaneous tissue, cross-sectional area) ultrasound characteristics of the three approaches for TP injection. In our sample, we observed significant differences among almost all the parameters of the three approaches, except for the safety window. Moreover, our analysis showed significant differences in cross-sectional area between treated and untreated. Advantages and disadvantages of each approach were investigated. Our findings can thus provide a suitable reference for clinical settings, especially for novice operators.

Transcranial Direct Current Stimulation Combined with Botulinum Neurotoxin Type A Injections for Treatment of Upper Limb Intention Tremor in Multiple Sclerosis: A Case Report.

Upper limb intention tremor is a common cause of disability in multiple sclerosis (MS). Transcranial direct current stimulation (tDCS) is an emerging form of brain stimulation used to improve sensorimotor impairments in many neurological disorders. Here, we describe a combined therapeutic approach with botulinum neurotoxin type A (BoNT-A) and tDCS for the treatment of upper limb tremor in a patient with MS. We administered a cathodal tDCS 15 days after the injections of BoNT-A. Both post-injection and post-stimulation evaluation revealed a considerable improvement of the tremor. This approach positively affected the patient's activities of daily living. Our case report shows a safe and beneficial effect of tDCS in the treatment of action tremor in MS especially as a possible adjunctive synergic treatment with BoNT-A injections.

Effectiveness of robotic balance training on postural instability in patients with mild Parkinson's disease: A pilot, single blind, randomized controlled trial.

OBJECTIVE: To examine whether tailored robotic platform training could improve postural stability compared with conventional balance treatment in patients with mild Parkinson's disease.  Design: Randomized single-blind pilot study. SUBJECTS: Twenty-two patients with mild Parkinson's disease (Hoehn and Yahr scale; HandY 1-2). METHODS: Patients were randomly assigned to an experimental group for robotic balance training and to a control group for conventional balance training. Each patient received 20 treatments (45 min/session, 5 times/week). Blinded evaluations were conducted before and after the treatment and 1 month post-treatment. Primary outcome measures were Mini BESTest, and Berg Balance Scale; secondary outcome measures were 10-Meter Walk Test, Five Times Sit to Stand Test, and Parkinson's Disease Questionnaire 39. RESULTS: Primary outcome measures in patients in both the experimental and control groups improved significantly after the balance treatment. Similar results were found for all the secondary outcome measures. The experimental group performed significantly better than the control group at both post-intervention and follow-up evaluation in the primary outcomes (p < 0.05). No significant differences be-tween groups were found in secondary outcomes. CONCLUSION: Robot-assisted balance training may be a promising tool to improve postural stability in patients with mild Parkinson's disease.

Discontinuation of botulinum neurotoxin type-A treatment during COVID-19 pandemic: an Italian survey in post stroke and traumatic brain injury patients living with spasticity.

BACKGROUND: The COVID-19 pandemic has affected health-care systems worldwide, including the outpatient spasticity care with botulinum neurotoxin toxin type A (BoNT-A). AIM: The aim of this study was to investigate the impact of discontinuation of BoNT-A treatment on patients living with spasticity during the COVID-19 quarantine. DESIGN: A multicentric cross-sectional study. SETTING: Outpatients setting. POPULATION: Patients with spasticity after stroke and traumatic brain injury treated with BoNT-A. METHODS: A phone-based survey was conducted from March to May, 2020. Based on the International Classification of Functioning, Disability and Health (ICF), an ad hoc questionnaire CORTOX (CORonavirus TOXin survey) was developed to investigate patients' experiences following the discontinuation of their usual treatment for spasticity due to the lockdown and its implication on their health perception. It assessed patients' condition and explored different ICF domains related to spasticity: unpleasant sensations, mobility, self-care, facilitators and psychosocial factors. The sum of those represented the CORTOX score (Max 142). The questionnaire also collected data about the impact of COVID-19 on patients' wellbeing (mood, sleep, relationships, community life, motivation). RESULTS: A total of 151 participants completed the survey. Most participants (72.2%) experienced a worsening in perceived spasticity, 53% got worse in independence and 70.9% had a negative impact on quality of life. The mean CORTOX score was 52.85±27.25, reflecting a perceived worsening in all ICF domains investigated. Moderate to strong correlations were found between different sub-scores of the questionnaire and severity of spasticity (P<0.001). COVID-19 psychosocial related factors were associated with loss of independence (P<0.05) but only mood was associated with worsening of spasticity (P<0.001). The lack of rehabilitation therapy was significantly associated with the worsening of independence but not with the worsening of spasticity. Finally, respondents reported that BoNT-A was useful to their condition and should not be discontinued. CONCLUSIONS: The discontinuation of BoNT-A treatment was associated with worsening of activities and participation and perceived spasticity. COVID-19 related problems and rehabilitation showed an association with loss of independence. CLINICAL REHABILITATION IMPACT: This study will provide useful information in the field of spasticity management using a patient's centred approach, with consistent quantitative and qualitative information.

Benefits of e-cigarettes in smoking reduction and in pulmonary health among chronic smokers undergoing a lung cancer screening program at 6 months.

INTRODUCTION: Electronic cigarettes (e-cigarettes) might be a valid and safe device to support smoking cessation. However, the available evidence is divergent. The aim of the present work was to assess the effects of an e-cigarette program on pulmonary health (cough, breath shortness, catarrh) and to evaluate the effectiveness of e-cigarettes in reducing tobacco consumption. METHODS: The study is a double-blind randomized controlled trial. Two hundred and ten smokers were randomized into three groups: nicotine e-cigarette (8 mg/mL nicotine concentration), nicotine-free e-cigarettes (placebo), and control with 1:1:1 ratio. All participants received a 3 months cessation program that included a cognitive-behavioral intervention aimed at supporting people in changing their behavior and improving motivation to quit. RESULTS: Pulmonary health, assessed with self-reported measures, clinical evaluations and the Leicester Cough Questionnaire, improved in participants who stopped smoking compared to their own baseline. No differences in pulmonary health were found between groups. Statistical tests showed a significant effect of Group (F (2, 118) = 4.005, p < .020) on daily cigarette consumption: after 6 months participants in the nicotine e-cigarette group smoked fewer cigarettes than any other group. Moreover, participants in this group showed the lowest level of exhaled carbon monoxide (CO) (M = 12.012, S.D. = 8.130), and the lowest level of dependence (M = 3.12, S.D. = 2.29) compared to the nicotine-free e-cigarette and control conditions. CONCLUSIONS: After 6 months about 20% of the entire sample stopped smoking. Participants who used e-cigarettes with nicotine smoked fewer tobacco cigarettes than any other group after 6 months (p < .020). Our data add to the efficacy and safety of e-cigarettes in helping smokers reducing tobacco consumption and improving pulmonary health status.

E-cigarettes May Support Smokers With High Smoking-Related Risk Awareness to Stop Smoking in the Short Run: Preliminary Results by Randomized Controlled Trial.

Introduction: E-cigarettes may be positively used in tobacco cessation treatments. However, neither the World Health Organization nor the American Food and Drug Administration has recognized them as effective cessation aids. Data about the efficacy and safety of e-cigarettes are still limited and controversial. Methods: This was a double-blind randomized controlled study. The main focus of this article is on a secondary outcome of the study, that is, the assessment of effectiveness and safety of e-cigarettes in achieving smoking cessation in a group of chronic smokers voluntarily involved in long-term lung cancer screening. Participants were randomized into three arms with a 1:1:1 ratio: e-cigarettes (Arm 1), placebo (Arm 2), and control (Arm 3). All subjects also received a low-intensity counseling. Results: Two hundred ten smokers were randomized (70 to nicotine e-cigarettes, 70 nicotine-free placebo e-cigarettes, and 70 to control groups). About 25% of participants who followed a cessation program based on the use of e-cigarettes (Arm 1 and Arm 2) were abstinent after 3 months. Conversely, only about 10% of smokers in Arm 3 stopped. A Kruskal-Wallis test showed significant differences in daily cigarettes smoking across the three arms (K-W = 6.277, p = .043). In particular, participants in Arm 1 reported a higher reduction rate (M = -11.6441, SD = 7.574) than participants in Arm 2 (M = -10.7636, SD = 8.156) and Arm 3 (M = -9.1379, SD = 8.8127). Conclusions: Our findings support the efficacy and safety of e-cigarettes in a short-term period. E-cigarettes use led to a higher cessation rate. Furthermore, although all participants reported a significant reduction of daily cigarette consumption compared to the baseline, the use of e-cigarettes (including those without nicotine) allowed smokers to achieve better results. Implications: E-cigarettes increased the stopping rate as well as the reduction of daily cigarettes in participants who continued smoking. In fact, although all participants reported a significant reduction of tobacco consumption compared to the baseline, the use of e-cigarettes allowed smokers to achieve a better result. It could be worthwhile to associate this device with new ICT-driven models of self-management support in order to enable people to better handle behavioral changes and side effects. This is true for ready-to-quit smokers (such as our participants) but can also be advantageous for less motivated smokers engaged in clinical settings.

Regulatory effects of estetrol on the endothelial plasminogen pathway and endothelial cell migration.

BACKGROUND: Estetrol (E4) is a natural estrogen produced solely during human pregnancy. E4 is suitable for clinical use since it acts as a selective estrogen receptor modulator. In clinical trials E4 has been seen to have little or no effect on coagulation. Hence, it is interesting to investigate whether E4 alters endothelial-dependent fibrinolysis. OBJECTIVES: We studied the effects of E4 on the fibrinolytic system and whether this could influence the ability of endothelial cells to migrate. In addition, we compared the effects of E4 with those of 17ß-estradiol (E2). STUDY DESIGN: Human umbilical vein endothelial cells (HUVEC) were obtained from healthy women. Expression of plasminogen-activator inhibitor-1 (PAI-1), urokinase-type plasminogen activator (u-PA) and tissue plasminogen activator (t-PA) proteins was evaluated by Western blot analysis. Endothelial cell migration was studied by razor-scrape horizontal and multiwell insert systems assays. RESULTS: E4 increased the expression of t-PA, u-PA and PAI-1 in HUVEC, but less so than did equimolar amounts of E2. The effects of E4 on t-PA, u-PA and PAI-1 were mediated by the induction of the early-immediate genes c-Jun and c-Fos. E4 in combination with E2 antagonized the effects induced by pregnancy-like E2 concentrations but did not impair the effects of postmenopausal-like E2 levels. We also found that the increased synthesis of PAI-1, u-PA and t-PA induced by E2 and E4 is important for horizontal and three-dimensional migration of HUVEC. CONCLUSIONS: These results support the hypothesis that E4 acts as an endogenous selective estrogen receptor modulator (SERM), controlling the fibrinolytic system and endothelial cell migration.