The Safety and Efficacy of Stem Cell Therapy as an Emerging Therapy for ALS: A Systematic Review of Controlled Clinical Trials

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with a heterogeneous course that ultimately leads to death. Currently, there is no cure, and new treatments that can slow the progression of the disease are needed. Stem cell (SC) transplantation is an emerging therapy that has shown a lot of potential in recent clinical trials. This review is aimed to examine the results of various clinical trials on this topic, thus assessing the safety and efficacy of SC transplantation as a potential treatment for ALS. We identified 748 studies in our search, of which 134 full-text studies were assessed for eligibility. Six studies met the inclusion criteria and were included in this review. Although some of the included studies showed the positive effect of SC transplantation, other studies found that there was no significant difference compared to the control group. We observed more positive effects with bone marrow mesenchymal stem cells (BM-MSC) treatments than Granulocyte colony-stimulating factor (G-CSF) ones. However, other factors, such as route of administration, number of doses, and number of cells per dose, could also play a role in this discrepancy. Based on this information, we conclude that more properly conducted clinical trials are needed to appreciate the benefit of this treatment.

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Breathalyser-Based eHealth Data Suggest That Self-Reporting of Abstinence Is a Poor Outcome Measure for Alcohol Use Disorder Clinical Trials

Alcohol and Alcoholism ◽

10.1093/alcalc/agaa004 ◽

2020 ◽

Vol 55 (3) ◽

pp. 237-245 ◽

Cited By ~ 1

Author(s):

Markku D Hämäläinen ◽

Andreas Zetterström ◽

Maria Winkvist ◽

Marcus Söderquist ◽

Patrik Öhagen ◽

...

Keyword(s):

Clinical Trials ◽

Alcohol Use ◽

Alcohol Use Disorder ◽

Outcome Measure ◽

Heavy Drinking ◽

Control Group ◽

Significant Difference ◽

And Control ◽

Positive Effect

Abstract Aims To evaluate the efficacy and monitoring capabilities of a breathalyser-based eHealth system for patients with alcohol use disorder (AUD) and to investigate the quality and validity of timeline follow-back (TLFB) as outcome measure in clinical trials and treatment. Methods Patients (n = 115) were recruited to clinical trials from a 12-step aftercare programme (12S-ABS) and from hospital care with abstinence (HC-ABS) or controlled drinking (HC-CDR) as goal and randomly divided into an eHealth and a control group. The effect of the eHealth system was analysed with TLFB-derived primary outcomes—change in number of abstinent days (AbsDay) and heavy drinking days (HDDs) compared to baseline—and phosphatidyl ethanol (PEth) measurements. Validity and quality of TLFB were evaluated by comparison with breath alcohol content (BrAC) and eHealth digital biomarkers (DBs): Addiction Monitoring Index (AMI) and Maximum Time Between Tests (MTBT). TLFB reports were compared to eHealth data regarding reported abstinence. Results The primary outcome (TLFB) showed no significant difference between eHealth and control groups, but PEth did show a significant difference especially at months 2 and 3. Self-reported daily abstinence suffered from severe quality issues: of the 28-day TLFB reports showing full abstinence eHealth data falsified 34% (BrAC measurements), 39% (MTBT), 54% (AMI) and 68% (BrAC/MTBT/AMI). 12S-ABS and HC-ABS patients showed severe under-reporting. Conclusions No effect of the eHealth system was measured with TLFB, but a small positive effect was measured with PEth. The eHealth system revealed severe quality problems with TLFB, especially regarding abstinence—should measurement-based eHealth data replace TLFB as outcome measure for AUD?

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Assessing the effects of methodological differences on outcomes in the use of psychedelics in the treatment of anxiety and depressive disorders: A systematic review and meta-analysis

Journal of Psychopharmacology ◽

10.1177/02698811211044688 ◽

2021 ◽

pp. 026988112110446

Author(s):

Robert F Leger ◽

Ellen M Unterwald

Keyword(s):

Clinical Trials ◽

Depressive Disorders ◽

Meta Analysis ◽

Multiple Dosing ◽

Positive Effects ◽

Cohen’S D ◽

Significant Difference ◽

Cohen's D ◽

Serotonin 2A ◽

Positive Effect

Background: Classical psychedelics are a group of drugs which act as agonists on the serotonin-2A (5-HT2A) receptor. Evidence suggests they may have a uniquely rapid and enduring positive effect on mood. However, marked heterogeneity between methodological designs in this emerging field remains a significant concern. Aims: To determine how differences in the type of psychedelic agent used and the number of dosing sessions administered affect subjects’ depression and anxiety outcomes and adverse drug reactions (ADR). Methods: This review collected and screened 1591 records from the MEDLINE and Web of Science databases for clinical trials reporting objective data on mood for subjects with a known anxiety or depression. Results: After screening, nine clinical trials met inclusion criteria. Meta-analysis of these studies showed significant, large positive effect sizes for measures of anxiety (Cohen’s d = 1.26) and depression (Cohen’s d = 1.38) overall. These positive effects were also significant at acute (⩽1 week) and extended (>1 week) time points. No significant differences were observed between trials using different psychedelic agents (psilocybin, ayahuasca or lysergic acid diethylamide (LSD)), however, a significant difference was observed in favour of trials with multiple dosing sessions. No serious ADR were reported. Conclusion: Psilocybin, ayahuasca and LSD all appear to be effective and relatively safe agents capable of producing rapid and sustained improvements in anxiety and depression. Moreover, the findings of the present analysis suggest that they may show a greater efficacy when given to patients over multiple sessions as compared to the more common single session used in many of the existing trials.

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In vitro study of human osteoblast proliferation and morphology on orthodontic mini-implants

The Angle Orthodontist ◽

10.2319/100714-717.1 ◽

2015 ◽

Vol 85 (6) ◽

pp. 920-926 ◽

Cited By ~ 2

Author(s):

Ricardo Carvalho Bueno ◽

Roberta Tarkany Basting

Keyword(s):

Chemical Composition ◽

In Vitro Study ◽

Chemical Components ◽

Control Group ◽

Osteoblast Proliferation ◽

Mini Implants ◽

Significant Difference ◽

Implant Anchorage ◽

Positive Effect

ABSTRACT Objective: To evaluate the proliferation and morphology of human osteoblasts cultured on two brands of mini-implants after 24, 48, and 72 hours, in addition to the chemical composition found on their surface. Materials and Methods: Two brands of mini-implant (Morelli and Neodent) were evaluated; polystyrene was used as a control group (n = 3). Osteoblasts were cultured on the surface of sterilized mini-implants in a CO2 incubator at different time periods (24, 48, and 72 hours). Osteoblast proliferation was quantified by scanning electron microscopy using up to 5000× magnification, and cell morphology was analyzed by a single observer. For the chemical analysis, spectroscopy X-ray fluorescence was used to identify and quantify chemical components on the surface of the mini-implants. Results: Two-way ANOVA showed no significant interaction between the factors studied (P = 0.686). A Tukey test revealed no significant difference in osteoblast proliferation between the mini-implants at all studied periods; however, a difference in cell proliferation was detected between the Neodent and the control group (P = .025). For all groups, time had a direct and positive effect on osteoblast proliferation (P < .001). The significant elements present in both brands of mini-implants were titanium, aluminum, vanadium, and iron. Conclusions: Osteoblast proliferation was present on the mini-implants studied, which increased over time; however, no significant difference between brands was observed. No difference was seen between the mini-implants evaluated in terms of chemical composition. Cell adhesion after 72 hours suggests that areas of bone remodeling can be achieved, thus initiating the process of mini-implant anchorage.

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The effect of the science classesenriched with art activities on academic achievementSanat etkinlikleri ile zenginleştirilmiş bilim uygulamaları dersinin akademik başarıya etkisi

Journal of Human Sciences ◽

10.14687/jhs.v14i2.4466 ◽

2017 ◽

Vol 14 (2) ◽

pp. 1469

Author(s):

Vesile Yıldız Demirtaş ◽

Seda Çerik ◽

Adem Maba

Keyword(s):

Academic Achievement ◽

Achievement Test ◽

Control Group ◽

Positive Effects ◽

Written Examination ◽

Significant Difference ◽

Post Test ◽

Quasi Experimental ◽

Elective Course ◽

Art Activities

The aim of the study is to reveal the effects of the classeswhich enriched with art activitieson academic achievement at the 5th grades. The research group consists of 37 students who determined the science applications course as an elective course in a public school in İzmir during 2015-2016 Education Fall Semester. In this study, from the trial models"Quasi-experimental desing, pre-post test without control group" was used. The data were collected with achievement test and written examination that prepared by researchers in order to measure academic achievement in science applications classes and also interviews that prepared by researchers used in order to determine the opinions of the students on the science applications enriched with art activities. As the results of the research there is a significant difference between the pretest-posttest findings and the pretest-permanency test results of the experimental group. As the results of the achievement test, it is concrete that these activities have positive effects on the students. It can be said that the applications are effective when the students' interview questions are compared with the answers given by the students after the last application. ÖzetAraştırmanın amacı 5. sınıflarda sanat etkinlikleri ile zenginleştirilmiş bilim uygulamaları dersinin akademik başarıya olan etkilerini ortaya çıkarmaktır. Araştırmanın çalışma grubunu 2015-2016 Öğretim Yılı Güz döneminde İzmir’de bir devlet okulunda bilim uygulamaları dersini seçmeli ders olarak belirleyen 37 öğrenci oluşturmaktadır.Bu araştırmada, deneme modellerinden “tek grup öntest-sontest kontrol grupsuz yarı deney deseni” kullanılmıştır. Veriler bilim uygulamaları dersindeki akademik başarıyı ölçmek amacıyla araştırmacılar tarafından hazırlanan bilim uygulamaları başarı testi ve yazılı yoklama ile öğrencilerin sanat etkinlikleri ile zenginleştirilmiş bilim uygulamaları dersine yönelik görüşlerini belirlemek amacıyla hazırlanan görüşme formu ile toplanmıştır.Araştırmada deney grubunun öntest-sontest sonuçlarında ve öntest-kalıcılık testi sonuçlarında anlamlı fark bulunmaktadır. Yapılan başarı testi sonucunda bu etkinliklerin öğrencileri olumlu etkilediği somut olarak ortaya çıkmıştır. Öğrencilerin görüşme sorularına ön uygulama ile son uygulama sonrası verdikleri cevaplar karşılaştırıldığında uygulamaların etkili olduğu söylenebilir.

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Haptic input and balance control: An exploratory study examining normative messaging

Journal of Health Psychology ◽

10.1177/1359105319877446 ◽

2019 ◽

pp. 135910531987744

Author(s):

Kevin S Spink ◽

Colin W Federow ◽

Joel L Lanovaz ◽

Alison R Oates

Keyword(s):

Exploratory Study ◽

Balance Control ◽

Analysis Of Covariance ◽

Control Group ◽

Descriptive Norm ◽

Significant Difference ◽

The Relationship ◽

Positive Effect ◽

Haptic Input

This study examined the effect of descriptive norm messaging information on the relationship between haptic input and balance control. Participants were randomly assigned to either a message group where they balanced with haptic input after receiving a descriptive norm message about the positive effect of haptic input or a control group. Findings from an analysis of covariance revealed a significant difference between the two groups. Those in the descriptive norm message group had better balance control than those in the control group. These findings suggest that efforts designed to improve balance control through haptic input may be enhanced through normative messaging.

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Cardiac Cell Therapies for the Treatment of Acute Myocardial Infarction: A Meta-Analysis from Mouse Studies

Cellular Physiology and Biochemistry ◽

10.1159/000477324 ◽

2017 ◽

Vol 42 (1) ◽

pp. 254-268 ◽

Cited By ~ 17

Author(s):

Cajetan Immanuel Lang ◽

Markus Wolfien ◽

Anne Langenbach ◽

Paula Müller ◽

Olaf Wolkenhauer ◽

...

Keyword(s):

Clinical Trials ◽

Stem Cell ◽

Mouse Model ◽

Left Ventricular ◽

Phase Iii ◽

Left Ventricular Ejection ◽

Ventricular Ejection Fraction ◽

Cell Therapies ◽

Positive Effects ◽

Advanced Therapies

Aims: Stem cell-based regenerative therapies for the treatment of ischemic myocardium are currently a subject of intensive investigation. A variety of cell populations have been demonstrated to be safe and to exert some positive effects in human Phase I and II clinical trials, however conclusive evidence of efficacy is still lacking. While the relevance of animal models for appropriate pre-clinical safety and efficacy testing with regard to application in Phase III studies continues to increase, concerns have been expressed regarding the validity of the mouse model to predict clinical results. Against the background that hundreds of preclinical studies have assessed the efficacy of numerous kinds of cell preparations - including pluripotent stem cells - for cardiac repair, we undertook a systematic re-evaluation of data from the mouse model, which initially paved the way for the first clinical trials in this field. Methods and Results: A systematic literature screen was performed to identify publications reporting results of cardiac stem cell therapies for the treatment of myocardial ischemia in the mouse model. Only peer-reviewed and placebo-controlled studies using magnet resonance imaging (MRI) for left ventricular ejection fraction (LVEF) assessment were included. Experimental data from 21 studies involving 583 animals demonstrate a significant improvement in LVEF of 8.59%+/- 2.36; p=.012 (95% CI, 3.7–13.8) compared with control animals. Conclusion: The mouse is a valid model to evaluate the efficacy of cell-based advanced therapies for the treatment of ischemic myocardial damage. Further studies are required to understand the mechanisms underlying stem cell based improvement of cardiac function after ischemia.

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Effects of Low-Frequency Cranial Electrostimulation on the Rest-Activity Rhythm and Salivary Cortisol in Alzheimer's Disease

Neurorehabilitation and Neural Repair ◽

10.1177/0888439003017002004 ◽

2003 ◽

Vol 17 (2) ◽

pp. 101-108 ◽

Cited By ~ 15

Author(s):

Erik Scherder ◽

Dirk Knol ◽

Eus van Someren ◽

Jan-Berend Deijen ◽

Rob Binnekade ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Activity Rhythm ◽

Low Frequency ◽

Control Group ◽

Positive Effects ◽

Alternative Research ◽

Positive Effect ◽

Experimental Group ◽

Rest Activity

Objective. In previous studies, cranial electrostimulation (CES) had positive effects on sleep in depressed patients and in patients with vascular dementia. The present study examined the effects of low-frequency CES on the rest-activity rhythm and cortisol levels of patients with probable Alzheimer's disease (AD). Method. It was hypothesised that a decreased level of cortisol would parallel a positive effect of low-frequency CES on nocturnal restlessness. Sixteen AD patients were randomly assigned to an experimental group (n = 8) or a control group (n = 8). The experimental group was treated with CES, whereas the control group received sham stimulation, for 30 minutes a day, during 6 weeks. The rest-activity rhythm was assessed by actigraphy. Cortisol was measured repeatedly in the saliva throughout the day by means of salivette tubes. Results. Low-frequency CES did not improve the rest-activity rhythm in AD patients. Moreover, both groups showed an increase instead of a decrease in the level of cortisol. Conclusions: These preliminary results suggest that low-frequency CES has no positive effect on the rest-activity rhythm in AD patients. An alternative research design with high-frequency CES in AD is discussed.

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The Reverse Remodeling Effect of Mesenchymal Stem Cells is Independent from the Site of Epimyocardial Cell Transplantation

Innovations Technology and Techniques in Cardiothoracic and Vascular Surgery ◽

10.1097/imi.0000000000000004 ◽

2013 ◽

Vol 8 (6) ◽

pp. 433-439 ◽

Cited By ~ 4

Author(s):

Mani Arsalan ◽

Stefan Dhein ◽

Heike Aupperle ◽

Ardawan Julian Rastan ◽

Markus Jan Barten ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Sham Group ◽

Heart Function ◽

Capillary Density ◽

Left Ventricular ◽

Reverse Remodeling ◽

Control Group ◽

Positive Effects ◽

Significant Difference

Objective The transplantation of mesenchymal stem cells (MSCs) represents a promising approach for treating the ischemic and the nonischemic diseased heart. The positive effects of transplanting these cells could be shown, but the exact mechanisms remain unknown. We evaluated whether the injection site affects the improvement in left ventricular (LV) ejection fraction (EF) and angiogenesis in doxorubicin (Dox)–induced failing hearts. Methods Heart failure was induced in New Zealand white rabbits by doxorubicin treatment, followed by right ventricular MSC transplantation (RV-MSC, n = 6), LV MSC transplantation (LV-MSC, n = 6), sham treatment (sham group, n = 6), or no therapy (Dox group, n = 5). Healthy rabbits were used as control group (n = 8). Cells were isolated after bone marrow aspiration and transplanted locally into the ventricular myocardium. After 4 weeks, cardiac function and capillary density (CD31 staining) were measured. Results The transplantation of MSCs increased the EF significantly (LV-MSC, 39.0% ± 1.4%, and RV-MSC, 39.2% ± 2.6%, vs sham group, 29.8% ± 3.7%; P < 0.001), without significance between the MSC groups ( P = 0.858). Neither the evidence of a transdifferentiation nor any signs of cell engraftment of transplanted cells could be found. The capillary density (capillaries/high-power field) increased in both MSC groups compared with the sham group (LV-MSC by 8.3% ± 3.4%; and RV-MSC, 8.1% ± 2.2%; P < 0.05), without significance between the two MSC groups ( P = 0.927). Conclusions Injection of autologous MSCs in doxorubicin-induced cardiomyopathic rabbit hearts improves EF and enhances angiogenesis. Despite local application, we observed global effects on heart function and capillary density without significant difference between right and LV injection. The paracrine mechanism might be one possible explanation for these findings.

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The Effect of Using the Care Model of "Sensitization" on Medication Adherence in Asthmatic Patients

Global Journal of Health Science ◽

10.5539/gjhs.v8n11p11 ◽

2016 ◽

Vol 8 (11) ◽

pp. 11 ◽

Cited By ~ 1

Author(s):

Mahbobeh Sajadi ◽

Mozhgan Bagheri ◽

Davood Hekmatpou ◽

Hamid Borsi

Keyword(s):

Medication Adherence ◽

T Test ◽

Control Group ◽

Care Model ◽

Chi Square ◽

Asthmatic Patients ◽

Significant Difference ◽

Prevalent Disease ◽

And Control ◽

Positive Effect

INTRODUCTION: Asthma is a prevalent disease with a multitude of complication. The present research was aimed at investigating the effects of implementing sensitization care model on medication adherence in asthmatic patients.METHODS & MATERIALS: In this interventional study, 74 subjects were selected using accessibility sampling method and were randomly classified into 2 separate groups, intervention (37 subjects) and control group (37 subjects). Data were collected with questionnaire. A month later, the subjects in both groups (control and intervention) completed questionnaire again. The collected data were analyzed using SPSS software, Independent t-test, Paired t-test and Chi-Square.RESULTS: Data analysis showed that the average age of participants was 41 years (range 21-83). The most and lowest frequencies of marital status in both sexes were 66.2% married and 33.8% single, respectively. There was no significant difference before intervention between two groups. However, after the intervention, there was a significant difference between the two groups (P=0.0001).DISCUSSION: The results of the present study showed that implementing sensitization care model had a positive effect on medication adherence among asthmatic patients. Therefore, application of this model is recommended to care and treatment asthmatic patients.

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The Role of Animal Models in Evaluating Reasonable Safety and Efficacy for Human Trials of Cell-Based Interventions for Neurologic Conditions

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.2008.98 ◽

2008 ◽

Vol 29 (1) ◽

pp. 1-9 ◽

Cited By ~ 23

Author(s):

Alan Regenberg ◽

Debra JH Mathews ◽

David M Blass ◽

Hilary Bok ◽

Joseph T Coyle ◽

...

Keyword(s):

Clinical Trials ◽

Animal Models ◽

Regenerative Medicine ◽

Therapeutic Agents ◽

Preclinical Studies ◽

Safety And Efficacy ◽

Proper Role ◽

New Treatments ◽

Gathering Data

Progress in regenerative medicine seems likely to produce new treatments for neurologic conditions that use human cells as therapeutic agents; at least one trial for such an intervention is already under way. The development of cell-based interventions for neurologic conditions (CBI-NCs) will likely include preclinical studies using animals as models for humans with conditions of interest. This paper explores predictive validity challenges and the proper role for animal models in developing CBI-NCs. In spite of limitations, animal models are and will remain an essential tool for gathering data in advance of first-in-human clinical trials. The goal of this paper is to provide a realistic lens for viewing the role of animal models in the context of CBI-NCs and to provide recommendations for moving forward through this challenging terrain.

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