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Neuroscience and Biobehavioral Reviews Aug 2015N-acetylcysteine (NAC) is recognized for its role in acetaminophen overdose and as a mucolytic. Over the past decade, there has been growing evidence for the use of NAC... (Review)
Review
N-acetylcysteine (NAC) is recognized for its role in acetaminophen overdose and as a mucolytic. Over the past decade, there has been growing evidence for the use of NAC in treating psychiatric and neurological disorders, considering its role in attenuating pathophysiological processes associated with these disorders, including oxidative stress, apoptosis, mitochondrial dysfunction, neuroinflammation and glutamate and dopamine dysregulation. In this systematic review we find favorable evidence for the use of NAC in several psychiatric and neurological disorders, particularly autism, Alzheimer's disease, cocaine and cannabis addiction, bipolar disorder, depression, trichotillomania, nail biting, skin picking, obsessive-compulsive disorder, schizophrenia, drug-induced neuropathy and progressive myoclonic epilepsy. Disorders such as anxiety, attention deficit hyperactivity disorder and mild traumatic brain injury have preliminary evidence and require larger confirmatory studies while current evidence does not support the use of NAC in gambling, methamphetamine and nicotine addictions and amyotrophic lateral sclerosis. Overall, NAC treatment appears to be safe and tolerable. Further well designed, larger controlled trials are needed for specific psychiatric and neurological disorders where the evidence is favorable.
Topics: Acetylcysteine; Adolescent; Adult; Clinical Trials as Topic; Female; Humans; Male; Mental Disorders; Nervous System Diseases; Neurology; Psychiatry; Randomized Controlled Trials as Topic; Treatment Outcome; Young Adult
PubMed: 25957927
DOI: 10.1016/j.neubiorev.2015.04.015 -
American Journal of Critical Care : An... Mar 2011In most diseases related to pleural effusion, the fluid analysis yields important diagnostic information, and in certain cases, fluid analysis alone is enough for... (Review)
Review
In most diseases related to pleural effusion, the fluid analysis yields important diagnostic information, and in certain cases, fluid analysis alone is enough for diagnosis. The many important characteristics of pleural fluid are described, as are other complementary investigations that can assist with the diagnosis of common and rare pleural effusions. For a systematic review of pleural effusion, a literature search for articles on the practical investigation and diagnosis of pleural effusion was done. Articles included guidelines, expert opinion, experimental and nonexperimental studies, literature reviews, and systematic reviews published from May 2003 through June 2009. The search yielded 1 guideline, 2 meta-analyses, 9 literature reviews, 1 randomized control trial, and 9 clinical studies. On the basis of class IIa or class I evidence from these articles, a step by step approach is recommended for investigating a pleural effusion, beginning with assessment of the medical history, clinical examination, radiology, pleural fluid evaluation, and finally, if no diagnosis is forthcoming, a pleural biopsy under image guidance or thoracoscopy.
Topics: Diagnostic Techniques and Procedures; Education, Medical, Continuing; Guidelines as Topic; Humans; Meta-Analysis as Topic; Pleural Effusion; Radiography; Randomized Controlled Trials as Topic
PubMed: 21362716
DOI: 10.4037/ajcc2011685 -
The International Journal of... 2014This review aimed to evaluate the documented clinical success of zirconia based crowns in clinical trials. (Review)
Review
PURPOSE
This review aimed to evaluate the documented clinical success of zirconia based crowns in clinical trials.
MATERIALS AND METHODS
Electronic databases were searched for original studies reporting on the clinical performance of tooth- or implant-supported zirconia-based crowns, including PubMed, Cochrane Library, and Science Direct. The electronic search was complemented by manual searches of the bibliographies of all retrieved full-text articles and reviews as well as a hand search of the following journals: International Journal of Prosthodontics, Journal of Oral Rehabilitation, International Journal of Oral & Maxillofacial Implants, and Clinical Oral Implants Research.
RESULTS
The search yielded 3,216 titles. Based on preestablished criteria, 42 full-text articles were obtained. While 16 studies fulfilled the inclusion criteria, only 3 randomized controlled trials were reported. Seven studies reported on tooth-supported and 4 on implant-supported crowns, and 5 studies reported on both types of support. Ten studies on tooth-supported and 7 on implant supported crowns provided sufficient material for statistical analysis. Life table analysis revealed cumulative 5-year survival rates of 95.9% for tooth-supported and 97.1% for implant-supported crowns. For implant-supported crowns, the most common reasons for failure were technical (veneering material fractures). For tooth-supported crowns, technical (veneering material fractures, loss of retention) and biologic (endodontic/ periodontic) reasons for failure were equally common. The most common complications for implant-supported crowns were veneering material fractures and bleeding on probing. For tooth-supported crowns, the most common complications were loss of retention, endodontic treatment, veneering material fractures, and bleeding on probing.
CONCLUSION
The results suggest that the success rate of tooth-supported and implant-supported zirconia-based crowns is adequate, similar, and comparable to that of conventional porcelain-fused-to-metal crowns. These results are, however, based on a relatively small number of studies, many that are not controlled clinical trials. Well-designed studies with large patient groups and long follow-up times are needed before general recommendations for the use of zirconia-based restorations can be provided.
Topics: Clinical Trials as Topic; Crowns; Dental Materials; Dental Prosthesis Design; Dental Prosthesis, Implant-Supported; Dental Restoration Failure; Humans; Randomized Controlled Trials as Topic; Treatment Outcome; Zirconium
PubMed: 24392475
DOI: 10.11607/ijp.3647 -
Amyotrophic Lateral Sclerosis :... 2009We have performed a systematic review to summarize current knowledge concerning factors related to survival in ALS and to evaluate the implications of these data for... (Review)
Review
We have performed a systematic review to summarize current knowledge concerning factors related to survival in ALS and to evaluate the implications of these data for clinical trials design. The median survival time from onset to death ranges from 20 to 48 months, but 10-20% of ALS patients have a survival longer than 10 years. Older age and bulbar onset are consistently reported to have a worse outcome. There are conflicting data on gender, diagnostic delay and El Escorial criteria. The rate of symptom progression was revealed to be an independent prognostic factor. Psychosocial factors, FTD, nutritional status, and respiratory function are also related to ALS outcome. The effect of enteral nutrition on survival is still unclear, while NIPPV has been found to improve survival. There are no well established biological markers of progression, although some are likely to emerge in the near future. These findings have relevant implications for the design of future trials. Randomization, besides the type of onset, should take into account age, respiratory status at entry, and a measure of disease progression pre-entry. Alternative trial designs can include the use of natural history controls, the so-called minimization method for treatment allocation, and the futility approach.
Topics: Age of Onset; Amyotrophic Lateral Sclerosis; Biomarkers; Clinical Trials as Topic; Disease Progression; Humans; Nutritional Status; Prognosis; Prospective Studies; Respiration; Retrospective Studies; Severity of Illness Index; Survival Rate
PubMed: 19922118
DOI: 10.3109/17482960802566824 -
BMC Neurology Mar 2014There are a number of instruments that describe severity and progression of multiple sclerosis and they are increasingly used as endpoints to assess the effectiveness of... (Review)
Review
Systematic literature review and validity evaluation of the Expanded Disability Status Scale (EDSS) and the Multiple Sclerosis Functional Composite (MSFC) in patients with multiple sclerosis.
BACKGROUND
There are a number of instruments that describe severity and progression of multiple sclerosis and they are increasingly used as endpoints to assess the effectiveness of therapeutic interventions. We examined to what extent the psychometric properties of two accepted instruments--EDSS and MSFC--meet methodological standards and the value they have in clinical trials.
METHODS
We conducted a systematic literature search in relevant databases [MEDLINE (PubMed), ISI Web of Science, EMBASE, PsycINFO & PSYNDEX, CINAHL] yielding 3,860 results. Relevant full-text publications were identified using abstract and then full-text reviews, and the literature was reviewed.
RESULTS
For evaluation of psychometric properties (validity, reliability, sensitivity of change) of EDSS and MSFC, 120 relevant full-text publications were identified, 54 of them assessed the EDSS, 26 the MSFC and 40 included both instruments. The EDSS has some documented weaknesses in reliability and sensitivity to change. The main limitations of the MSFC are learning effects and the z-scores method used to calculate the total score. However, the methodological criterion of validity applies sufficiently for both instruments.For use in clinical studies, we found the EDSS to be preferred as a primary and secondary outcome measure in recent studies (50 EDSS, 9 MSFC).
CONCLUSIONS
Recognizing their strengths and weaknesses, both EDSS and MSFC are suitable to detect the effectiveness of clinical interventions and to monitor disease progression. Almost all publications identify the EDSS as the most widely used tool to measure disease outcomes in clinical trials. Despite some limitations, both instruments are accepted as endpoints and neither are discussed as surrogate parameters in identified publications. A great advantage of the EDSS is its international acceptance (e.g. by EMA) as a primary endpoint in clinical trials and its broad use in trials, enabling cross-study comparisons.
Topics: Clinical Trials as Topic; Disability Evaluation; Humans; Multiple Sclerosis; Psychometrics
PubMed: 24666846
DOI: 10.1186/1471-2377-14-58 -
Critical Care (London, England) Apr 2015Despite recommendations from professional societies and patient safety organizations, the majority of ICU patients worldwide are not routinely monitored for delirium,... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Despite recommendations from professional societies and patient safety organizations, the majority of ICU patients worldwide are not routinely monitored for delirium, thus preventing timely prevention and management. The purpose of this systematic review is to summarize what types of implementation strategies have been tested to improve ICU clinicians' ability to effectively assess, prevent and treat delirium and to evaluate the effect of these strategies on clinical outcomes.
METHOD
We searched PubMed, Embase, PsychINFO, Cochrane and CINAHL (January 2000 and April 2014) for studies on implementation strategies that included delirium-oriented interventions in adult ICU patients. Studies were suitable for inclusion if implementation strategies' efficacy, in terms of a clinical outcome, or process outcome was described.
RESULTS
We included 21 studies, all including process measures, while 9 reported both process measures and clinical outcomes. Some individual strategies such as "audit and feedback" and "tailored interventions" may be important to establish clinical outcome improvements, but otherwise robust data on effectiveness of specific implementation strategies were scarce. Successful implementation interventions were frequently reported to change process measures, such as improvements in adherence to delirium screening with up to 92%, but relating process measures to outcome changes was generally not possible. In meta-analyses, reduced mortality and ICU length of stay reduction were statistically more likely with implementation programs that employed more (six or more) rather than less implementation strategies and when a framework was used that either integrated current evidence on pain, agitation and delirium management (PAD) or when a strategy of early awakening, breathing, delirium screening and early exercise (ABCDE bundle) was employed. Using implementation strategies aimed at organizational change, next to behavioral change, was also associated with reduced mortality.
CONCLUSION
Our findings may indicate that multi-component implementation programs with a higher number of strategies targeting ICU delirium assessment, prevention and treatment and integrated within PAD or ABCDE bundle have the potential to improve clinical outcomes. However, prospective confirmation of these findings is needed to inform the most effective implementation practice with regard to integrated delirium management and such research should clearly delineate effective practice change from improvements in clinical outcomes.
Topics: Clinical Trials as Topic; Critical Care; Delirium; Disease Management; Humans; Intensive Care Units; Treatment Outcome
PubMed: 25888230
DOI: 10.1186/s13054-015-0886-9 -
British Journal of Sports Medicine Apr 2017To examine the effects of stepping interventions on fall risk factors and fall incidence in older people. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To examine the effects of stepping interventions on fall risk factors and fall incidence in older people.
DATA SOURCE
Electronic databases (PubMed, EMBASE, CINAHL, Cochrane, CENTRAL) and reference lists of included articles from inception to March 2015.
STUDY SELECTION
Randomised (RCT) or clinical controlled trials (CCT) of volitional and reactive stepping interventions that included older (minimum age 60) people providing data on falls or fall risk factors.
RESULTS
Meta-analyses of seven RCTs (n=660) showed that the stepping interventions significantly reduced the rate of falls (rate ratio=0.48, 95% CI 0.36 to 0.65, p<0.0001, I=0%) and the proportion of fallers (risk ratio=0.51, 95% CI 0.38 to 0.68, p<0.0001, I=0%). Subgroup analyses stratified by reactive and volitional stepping interventions revealed a similar efficacy for rate of falls and proportion of fallers. A meta-analysis of two RCTs (n=62) showed that stepping interventions significantly reduced laboratory-induced falls, and meta-analysis findings of up to five RCTs and CCTs (n=36-416) revealed that stepping interventions significantly improved simple and choice stepping reaction time, single leg stance, timed up and go performance (p<0.05), but not measures of strength.
CONCLUSIONS
The findings indicate that both reactive and volitional stepping interventions reduce falls among older adults by approximately 50%. This clinically significant reduction may be due to improvements in reaction time, gait, balance and balance recovery but not in strength. Further high-quality studies aimed at maximising the effectiveness and feasibility of stepping interventions are required.
SYSTEMATIC REVIEWS REGISTRATION NUMBER
CRD42015017357.
Topics: Accidental Falls; Aged; Controlled Clinical Trials as Topic; Gait; Humans; Middle Aged; Physical Therapy Modalities; Postural Balance; Randomized Controlled Trials as Topic; Reaction Time
PubMed: 26746905
DOI: 10.1136/bjsports-2015-095452 -
Orthodontics & Craniofacial Research Nov 2018The aim of this review was to evaluate available evidence on the effect of early orthodontic management and myofunctional treatment in the developing dentition children,... (Meta-Analysis)
Meta-Analysis
Effect of orthodontic management and orofacial muscle training protocols on the correction of myofunctional and myoskeletal problems in developing dentition. A systematic review and meta-analysis.
The aim of this review was to evaluate available evidence on the effect of early orthodontic management and myofunctional treatment in the developing dentition children, on anterior open bite correction, as well as on normalization of patterns of mouth breathing, swallowing and tongue resting position and pressure. Electronic searches in MEDLINE, Cochrane and LILACS, without language restrictions were conducted. Additionally, unpublished literature was identified. Randomized controlled trials, or controlled clinical trials, comparing interventions applied to manage anterior open bite and other muscle functions such as breathing/swallowing pattern and tongue resting position and pressure, were considered. Quality assessment was based on the Cochrane Risk of Bias tool. Random effects meta-analyses were conducted to assess treatment effects. From the 265 initial search results, 15 articles were included in the review. Eight were randomized controlled trials (RCTs) and 7 were controlled clinical trials. Treatment outcomes comprised skeletal and dentoalveolar changes recorded cephalometrically, mouth posture and lip closure normalization, improvement of tongue resting position/pressure and modification of swallowing pattern. Quantitative synthesis was possible for only 2 of the included RCTs. There was no evidence to support bonded lingual spurs over banded fixed appliances for the correction of anterior open bite in mixed dentition children presenting nonnutritive oral habits at the onset of treatment (SMD: -0.03; 95%CI: -.81, 0.74; P = 0.94). Although early orthodontic management and myofunctional treatment in the deciduous and mixed dentition children appears to be a promising approach, the quality of the existing evidence is questionable.
Topics: Humans; Cephalometry; Controlled Clinical Trials as Topic; Databases, Factual; Deglutition; Dentition, Mixed; Facial Muscles; Malocclusion; Mouth Breathing; Myofunctional Therapy; Open Bite; Orthodontic Appliances, Fixed; Orthodontic Appliances, Functional; Randomized Controlled Trials as Topic; Tongue; Tooth, Deciduous; Treatment Outcome
PubMed: 30152171
DOI: 10.1111/ocr.12240 -
Alimentary Pharmacology & Therapeutics Aug 2018Fibrotic stricture is a common complication of Crohn's disease (CD) affecting approximately half of all patients. No specific anti-fibrotic therapies are available;...
BACKGROUND
Fibrotic stricture is a common complication of Crohn's disease (CD) affecting approximately half of all patients. No specific anti-fibrotic therapies are available; however, several therapies are currently under evaluation. Drug development for the indication of stricturing CD is hampered by a lack of standardised definitions, diagnostic modalities, clinical trial eligibility criteria, endpoints and treatment targets in stricturing CD.
AIM
To standardise definitions, diagnosis and treatment targets for anti-fibrotic stricture therapies in Chron's disease.
METHODS
An interdisciplinary expert panel consisting of 15 gastroenterologists and radiologists was assembled. Using modified RAND/University of California Los Angeles appropriateness methodology, 109 candidate items derived from systematic review and expert opinion focusing on small intestinal strictures were anonymously rated as inappropriate, uncertain or appropriate. Survey results were discussed as a group before a second and third round of voting.
RESULTS
Fibrotic strictures are defined by the combination of luminal narrowing, wall thickening and pre-stenotic dilation. Definitions of anastomotic (at site of prior intestinal resection with anastomosis) and naïve small bowel strictures were similar; however, there was uncertainty regarding wall thickness in anastomotic strictures. Magnetic resonance imaging is considered the optimal technique to define fibrotic strictures and assess response to therapy. Symptomatic strictures are defined by abdominal distension, cramping, dietary restrictions, nausea, vomiting, abdominal pain and post-prandial abdominal pain. Need for intervention (endoscopic balloon dilation or surgery) within 24-48 weeks is considered the appropriate endpoint in pharmacological trials.
CONCLUSIONS
Consensus criteria for diagnosis and response to therapy in stricturing Crohn's disease should inform both clinical practice and trial design.
Topics: Catheterization; Clinical Trials as Topic; Colon; Consensus; Constriction, Pathologic; Crohn Disease; Dilatation; Endoscopy; Expert Testimony; Fibrosis; Humans; Intestinal Obstruction; Intestine, Small; Practice Guidelines as Topic; Reference Standards
PubMed: 29920726
DOI: 10.1111/apt.14853 -
The Journal of Pain 2020Fibromyalgia is a debilitating condition characterized by chronic widespread pain. It is believed to be caused by dysfunction of the central nervous system (CNS) but... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Fibromyalgia is a debilitating condition characterized by chronic widespread pain. It is believed to be caused by dysfunction of the central nervous system (CNS) but current treatments are largely ineffective. Transcranial direct current stimulation (tDCS), a neuromodulation technique that targets the CNS, may offer a new line of treatment.
OBJECTIVE
To systematically review the most up-to-date literature and perform a meta-analysis of the effects of tDCS on pain intensity in fibromyalgia.
METHODS
The following databases were searched from inception: Medline (Ovid), PsychInfo, CINAHL, Cochrane Library, and Web of Science. Studies were eligible if they were randomized controlled trials, quasi-randomized trials, and nonrandomized. Crossover and parallel-group design studies were included. Risk of bias was assessed for all included studies. Meta-analysis was conducted on studies investigating pain intensity after tDCS in participants with fibromyalgia and analyzed using standardized mean difference and 95% confidence intervals.
RESULTS
Fourteen clinical studies were included. Ten were controlled trials and 4 were within-subjects crossover studies. Meta-analysis of data from 8 controlled trials provides tentative evidence of pain reduction when active tDCS is delivered compared to sham. However, substantial statistical heterogeneity and high risk of bias of primary studies prevent more conclusive recommendations being made.
CONCLUSIONS
tDCS is a safe intervention with the potential to lower pain intensity in fibromyalgia. However, there is a need for more empirical research of the neural target sites and optimum stimulation parameters to achieve the greatest effects before conducting further clinical studies.
PERSPECTIVE
This systematic review and meta-analysis synthesizes current evidence for the clinical effectiveness of tDCS in the treatment of fibromyalgia pain. There is only tentative evidence of pain reduction when active tDCS is compared to sham. High heterogeneity and risk of bias across studies suggest a need for further empirical research.
Topics: Chronic Pain; Clinical Trials as Topic; Fibromyalgia; Humans; Pain Management; Transcranial Direct Current Stimulation; Treatment Outcome
PubMed: 31982685
DOI: 10.1016/j.jpain.2020.01.003