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Medicina (Kaunas, Lithuania) Oct 2021Early osteoarthritis (EOA) still represents a challenge for clinicians. Although there is no consensus on its definition and diagnosis, a prompt therapeutic intervention... (Review)
Review
Early osteoarthritis (EOA) still represents a challenge for clinicians. Although there is no consensus on its definition and diagnosis, a prompt therapeutic intervention in the early stages can have a significant impact on function and quality of life. Exercise remains a core treatment for EOA; however, several physical modalities are commonly used in this population. The purpose of this paper is to investigate the role of physical agents in the treatment of EOA. A technical expert panel (TEP) of 8 medical specialists with expertise in physical agent modalities and musculoskeletal conditions performed the review following the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews) model. The TEP searched for evidence of the following physical modalities in the management of EOA: "Electric Stimulation Therapy", "Pulsed Electromagnetic field", "Low-Level Light Therapy", "Laser Therapy", "Magnetic Field Therapy", "Extracorporeal Shockwave Therapy", "Hyperthermia, Induced", "Cryotherapy", "Vibration therapy", "Whole Body Vibration", "Physical Therapy Modalities". We found preclinical and clinical data on transcutaneous electrical nerve stimulation (TENS), extracorporeal shockwave therapy (ESWT), low-intensity pulsed ultrasound (LIPUS), pulsed electromagnetic fields stimulation (PEMF), and whole-body vibration (WBV) for the treatment of knee EOA. We found two clinical studies about TENS and PEMF and six preclinical studies-three about ESWT, one about WBV, one about PEMF, and one about LIPUS. The preclinical studies demonstrated several biological effects on EOA of physical modalities, suggesting potential disease-modifying effects. However, this role should be better investigated in further clinical studies, considering the limited data on the use of these interventions for EOA patients.
Topics: Electric Stimulation Therapy; Humans; Magnetic Field Therapy; Osteoarthritis, Knee; Physical Therapy Modalities; Quality of Life
PubMed: 34833383
DOI: 10.3390/medicina57111165 -
World Journal of Gastroenterology May 2010This article reviews the evidence for efficacy and safety of Saccharomyces boulardii (S. boulardii) for various disease indications in adults based on the peer-reviewed,... (Meta-Analysis)
Meta-Analysis Review
This article reviews the evidence for efficacy and safety of Saccharomyces boulardii (S. boulardii) for various disease indications in adults based on the peer-reviewed, randomized clinical trials and pre-clinical studies from the published medical literature (Medline, Clinical Trial websites and meeting abstracts) between 1976 and 2009. For meta-analysis, only randomized, blinded controlled trials unrestricted by language were included. Pre-clinical studies, volunteer studies and uncontrolled studies were excluded from the review of efficacy and meta-analysis, but included in the systematic review. Of 31 randomized, placebo-controlled treatment arms in 27 trials (encompassing 5029 study patients), S. boulardii was found to be significantly efficacious and safe in 84% of those treatment arms. A meta-analysis found a significant therapeutic efficacy for S. boulardii in the prevention of antibiotic-associated diarrhea (AAD) (RR = 0.47, 95% CI: 0.35-0.63, P < 0.001). In adults, S. boulardii can be strongly recommended for the prevention of AAD and the traveler's diarrhea. Randomized trials also support the use of this yeast probiotic for prevention of enteral nutrition-related diarrhea and reduction of Helicobacter pylori treatment-related symptoms. S. boulardii shows promise for the prevention of C. difficile disease recurrences; treatment of irritable bowel syndrome, acute adult diarrhea, Crohn's disease, giardiasis, human immunodeficiency virus-related diarrhea; but more supporting evidence is recommended for these indications. The use of S. boulardii as a therapeutic probiotic is evidence-based for both efficacy and safety for several types of diarrhea.
Topics: Adult; Anti-Bacterial Agents; Contraindications; Diarrhea; Enteral Nutrition; Evidence-Based Medicine; Humans; Intestinal Diseases; Intestines; Practice Guidelines as Topic; Probiotics; Saccharomyces; Travel; Treatment Outcome
PubMed: 20458757
DOI: 10.3748/wjg.v16.i18.2202 -
Pain Jul 2021This narrative review represents an output from the International Association for the Study of Pain's global task force on the use of cannabis, cannabinoids, and... (Meta-Analysis)
Meta-Analysis
This narrative review represents an output from the International Association for the Study of Pain's global task force on the use of cannabis, cannabinoids, and cannabis-based medicines for pain management, informed by our companion systematic review and meta-analysis of preclinical studies in this area. Our aims in this review are (1) to describe the value of studying cannabinoids and endogenous cannabinoid (endocannabinoid) system modulators in preclinical/animal models of pain; (2) to discuss both pain-related efficacy and additional pain-relevant effects (adverse and beneficial) of cannabinoids and endocannabinoid system modulators as they pertain to animal models of pathological or injury-related persistent pain; and (3) to identify important directions for future research. In service of these goals, this review (1) provides an overview of the endocannabinoid system and the pharmacology of cannabinoids and endocannabinoid system modulators, with specific relevance to animal models of pathological or injury-related persistent pain; (2) describes pharmacokinetics of cannabinoids in rodents and humans; and (3) highlights differences and discrepancies between preclinical and clinical studies in this area. Preclinical (rodent) models have advanced our understanding of the underlying sites and mechanisms of action of cannabinoids and the endocannabinoid system in suppressing nociceptive signaling and behaviors. We conclude that substantial evidence from animal models supports the contention that cannabinoids and endocannabinoid system modulators hold considerable promise for analgesic drug development, although the challenge of translating this knowledge into clinically useful medicines is not to be underestimated.
Topics: Animals; Cannabinoid Receptor Modulators; Cannabinoids; Cannabis; Endocannabinoids; Pain; Pain Management; Receptors, Cannabinoid
PubMed: 33729211
DOI: 10.1097/j.pain.0000000000002268 -
Orthopaedic Journal of Sports Medicine Oct 2018Recent investigations on the biochemical pathways after a musculoskeletal injury have suggested that vitamin C (ascorbic acid) may be a viable supplement to enhance... (Review)
Review
BACKGROUND
Recent investigations on the biochemical pathways after a musculoskeletal injury have suggested that vitamin C (ascorbic acid) may be a viable supplement to enhance collagen synthesis and soft tissue healing.
PURPOSE
To (1) summarize vitamin C treatment protocols; (2) report on the efficacy of vitamin C in accelerating healing after bone, tendon, and ligament injuries in vivo and in vitro; and (3) report on the efficacy of vitamin C as an antioxidant protecting against fibrosis and promoting collagen synthesis.
STUDY DESIGN
Systematic review; Level of evidence, 2.
METHODS
A systematic review was performed, with the inclusion criteria of animal and human studies on vitamin C supplementation after a musculoskeletal injury specific to collagen cross-linking, collagen synthesis, and biologic healing of the bone, ligament, and tendon.
RESULTS
The initial search yielded 286 articles. After applying the inclusion and exclusion criteria, 10 articles were included in the final analysis. Of the preclinical studies evaluating fracture healing, 2 studies reported significantly accelerated bone healing in the vitamin C supplementation group compared with control groups. The 2 preclinical studies evaluating tendon healing reported significant increases in type I collagen fibers and scar tissue formation with vitamin C compared with control groups. The 1 preclinical study after anterior cruciate ligament (ACL) reconstruction reported significant short-term (1-6 weeks) improvements in ACL graft incorporation in the vitamin C group compared with control groups; however, there was no long-term (42 weeks) difference. Of the clinical studies evaluating fracture healing, 1 study reported no significant differences in the rate of fracture healing at 50 days or functional outcomes at 1 year. Vitamin C supplementation was shown to decrease oxidative stress parameters by neutralizing reactive oxygen species through redox modulation in animal models. No animal or human studies reported any adverse effects of vitamin C supplementation.
CONCLUSION
Preclinical studies demonstrated that vitamin C has the potential to accelerate bone healing after a fracture, increase type I collagen synthesis, and reduce oxidative stress parameters. No adverse effects were reported with vitamin C supplementation in either animal models or human participants; thus, oral vitamin C appears to be a safe supplement but lacks clinical evidence compared with controls. Because of the limited number of human studies, further clinical investigations are needed before the implementation of vitamin C as a postinjury supplement.
PubMed: 30386805
DOI: 10.1177/2325967118804544 -
Alzheimer's Research & Therapy Jan 2019Alzheimer's disease (AD) pathology begins several years before the clinical onset. The long preclinical phase is composed of three stages according to the 2011National... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Alzheimer's disease (AD) pathology begins several years before the clinical onset. The long preclinical phase is composed of three stages according to the 2011National Institute on Aging and Alzheimer's Association (NIA-AA) criteria, followed by mild cognitive impairment (MCI), a featured clinical entity defined as "due to AD", or "prodromal AD", when pathophysiological biomarkers (i.e., cerebrospinal fluid or positron emission tomography with amyloid tracer) are positive. In the clinical setting, there is a clear need to detect the earliest symptoms not yet fulfilling MCI criteria, in order to proceed to biomarker assessment for diagnostic definition, thus offering treatment with disease-modifying drugs to patients as early as possible. According to the available evidence, we thus estimated the prevalence and risk of progression at each preclinical AD stage, with special interest in Stage 3.
METHODS
Cross-sectional and longitudinal studies published from April 2008 to May 2018 were obtained through MEDLINE-PubMed, screened, and systematically reviewed by four independent reviewers. Data from included studies were meta-analyzed using random-effects models. Heterogeneity was assessed by I statistics.
RESULTS
Estimated overall prevalence of preclinical AD was 22% (95% CI = 18-26%). Rate of biomarker positivity overlapped in cognitively normal individuals and people with subjective cognitive decline. The risk of progression increases across preclinical AD stages, with individuals classified as NIA-AA Stage 3 showing the highest risk (73%, 95% CI = 40-92%) compared to those in Stage 2 (38%, 95% CI = 21-59%) and Stage 1 (20%, 95% CI = 10-34%).
CONCLUSION
Available data consistently show that risk of progression increases across the preclinical AD stages, where Stage 3 shows a risk of progression comparable to MCI due to AD. Accordingly, an effort should be made to also operationalize the diagnostic work-up in subjects with subtle cognitive deficits not yet fulfilling MCI criteria. The possibility to define, in the clinical routine, a patient as "pre-MCI due to AD" could offer these subjects the opportunity to use disease-modifying drugs at best.
Topics: Alzheimer Disease; Cross-Sectional Studies; Disease Progression; Humans; Longitudinal Studies; Prevalence; Prodromal Symptoms; Risk Factors
PubMed: 30646955
DOI: 10.1186/s13195-018-0459-7 -
Frontiers in Cellular and Infection... 2022Many individuals diagnosed with autism spectrum disorder (ASD) experience gastrointestinal (GI) dysfunction and show microbial dysbiosis. Variation in gut microbial... (Review)
Review
Many individuals diagnosed with autism spectrum disorder (ASD) experience gastrointestinal (GI) dysfunction and show microbial dysbiosis. Variation in gut microbial populations is associated with increased risk for GI symptoms such as chronic constipation and diarrhoea, which decrease quality of life. Several preclinical models of autism also demonstrate microbial dysbiosis. Given that much pre-clinical research is conducted in mouse models, it is important to understand the similarities and differences between the gut microbiome in humans and these models in the context of autism. We conducted a systematic review of the literature using PubMed, ProQuest and Scopus databases to compare microbiome profiles of patients with autism and transgenic (NL3, Shank3 KO, 15q dup), phenotype-first (BTBR) and environmental (Poly I:C, Maternal Inflammation Activation (MIA), valproate) mouse models of autism. Overall, we report changes in fecal microbial communities relevant to ASD based on both clinical and preclinical studies. Here, we identify an overlapping cluster of genera that are modified in both fecal samples from individuals with ASD and mouse models of autism. Specifically, we describe an increased abundance of , , and and a decrease in genera in both humans and rodents relevant to this disorder. Studies in both humans and mice highlighted multidirectional changes in abundance (i.e. in some cases increased abundance whereas other reports showed decreases) for several genera including , , , and , suggesting that these genera may be susceptible to modification in autism. Identification of these microbial profiles may assist in characterising underlying biological mechanisms involving host-microbe interactions and provide future therapeutic targets for improving gut health in autism.
Topics: Animals; Autism Spectrum Disorder; Autistic Disorder; Disease Models, Animal; Dysbiosis; Gastrointestinal Diseases; Gastrointestinal Microbiome; Humans; Mice; Microfilament Proteins; Nerve Tissue Proteins; Quality of Life
PubMed: 35846755
DOI: 10.3389/fcimb.2022.905841 -
The Annals of Pharmacotherapy Feb 2023The objective of this systematic review is to summarize in vitro, preclinical, and human data related to omadacycline and infection (CDI). (Review)
Review
OBJECTIVE
The objective of this systematic review is to summarize in vitro, preclinical, and human data related to omadacycline and infection (CDI).
DATA SOURCES
PubMed and Google Scholar were searched for "omadacycline" AND ("" OR "" OR "") for any studies published before February 15, 2022. The US Food and Drug Administration (FDA) Adverse Events Reporting System (AERS) was searched for omadacycline (for reports including "" or "CDI" or "gastrointestinal infection"). The publications list publicly available at Paratek Pharmaceuticals, Inc. Web site was reviewed.
STUDY SELECTION AND DATA EXTRACTION
Publications presenting primary data on omadacycline and published in English were included.
DATA SYNTHESIS
Preclinical and clinical evidence was extracted from 14 studies. No case reports in indexed literature and no reports on FDA AERS were found. Omadacycline has potent in vitro activity against many clinical strains and diverse ribotypes. In phase 3 studies, there were no reports of CDI in patients who received omadacycline for either community-acquired bacterial pneumonia or acute bacterial skin and skin structure infection.
RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE
Omadacycline should be considered a low-risk antibiotic regarding its propensity to cause CDI.
CONCLUSIONS
Reducing the burden of CDI on patients and the health care system should be a priority. Patients with appropriate indications who are at heightened risk of CDI may be suitable candidates for omadacycline therapy. In these patients, omadacycline may be preferable to antibiotics with a high CDI risk.
Topics: Humans; Clostridioides; Anti-Bacterial Agents; Clostridium Infections; Clostridioides difficile; Bacteria; Community-Acquired Infections
PubMed: 35656828
DOI: 10.1177/10600280221089007 -
Neuroscience and Biobehavioral Reviews Sep 2016Rodent defense behavior assays have been widely used as preclinical models of anxiety to study possibly therapeutic anxiety-reducing interventions. However, some... (Meta-Analysis)
Meta-Analysis Review
Rodent defense behavior assays have been widely used as preclinical models of anxiety to study possibly therapeutic anxiety-reducing interventions. However, some proposed anxiety-modulating factors - genes, drugs and stressors - have had discordant effects across different studies. To reconcile the effect sizes of purported anxiety factors, we conducted systematic review and meta-analyses of the literature on ten anxiety-linked interventions, as examined in the elevated plus maze, open field and light-dark box assays. Diazepam, 5-HT1A receptor gene knockout and overexpression, SERT gene knockout and overexpression, pain, restraint, social isolation, corticotropin-releasing hormone and Crhr1 were selected for review. Eight interventions had statistically significant effects on rodent anxiety, while Htr1a overexpression and Crh knockout did not. Evidence for publication bias was found in the diazepam, Htt knockout, and social isolation literatures. The Htr1a and Crhr1 results indicate a disconnect between preclinical science and clinical research. Furthermore, the meta-analytic data confirmed that genetic SERT anxiety effects were paradoxical in the context of the clinical use of SERT inhibitors to reduce anxiety.
Topics: Anxiety; Anxiety Disorders; Corticotropin-Releasing Hormone; Humans; Receptors, Corticotropin-Releasing Hormone; Social Isolation
PubMed: 27328783
DOI: 10.1016/j.neubiorev.2016.04.011 -
Journal of Cerebral Blood Flow and... May 2014The use of systematic review and meta-analysis of preclinical studies has become more common, including those of studies describing the modeling of cerebrovascular... (Review)
Review
The use of systematic review and meta-analysis of preclinical studies has become more common, including those of studies describing the modeling of cerebrovascular diseases. Empirical evidence suggests that too many preclinical experiments lack methodological rigor, and this leads to inflated treatment effects. The aim of this review is to describe the concepts of systematic review and meta-analysis and consider how these tools may be used to provide empirical evidence to spur the field to improve the rigor of the conduct and reporting of preclinical research akin to their use in improving the conduct and reporting of randomized controlled trials in clinical research. As with other research domains, systematic reviews are subject to bias. Therefore, we have also suggested guidance for their conduct, reporting, and critical appraisal.
Topics: Animals; Bias; Disease Models, Animal; Drug Evaluation, Preclinical; Humans; Meta-Analysis as Topic; Review Literature as Topic; Stroke; Translational Research, Biomedical
PubMed: 24549183
DOI: 10.1038/jcbfm.2014.28 -
Pharmacological Reviews Jan 2022A widely held dogma in the preclinical addiction field is that females are more vulnerable than males to drug craving and relapse. Here, we first review clinical studies... (Review)
Review
A widely held dogma in the preclinical addiction field is that females are more vulnerable than males to drug craving and relapse. Here, we first review clinical studies on sex differences in psychostimulant and opioid craving and relapse. Next, we review preclinical studies on sex differences in psychostimulant and opioid reinstatement of drug seeking after extinction of drug self-administration, and incubation of drug craving (time-dependent increase in drug seeking during abstinence). We also discuss ovarian hormones' role in relapse and craving in humans and animal models and speculate on brain mechanisms underlying their role in cocaine craving and relapse in rodent models. Finally, we discuss imaging studies on brain responses to cocaine cues and stress in men and women.The results of the clinical studies reviewed do not appear to support the notion that women are more vulnerable to psychostimulant and opioid craving and relapse. However, this conclusion is tentative because most of the studies reviewed were correlational, not sufficiently powered, and not a priori designed to detect sex differences. Additionally, imaging studies suggest sex differences in brain responses to cocaine cues and stress. The results of the preclinical studies reviewed provide evidence for sex differences in stress-induced reinstatement and incubation of cocaine craving but not cue- or cocaine-induced reinstatement of cocaine seeking. These sex differences are modulated in part by ovarian hormones. In contrast, the available data do not support the notion of sex differences in craving and relapse/reinstatement for methamphetamine or opioids in rodent models. SIGNIFICANCE STATEMENT: This systematic review summarizes clinical and preclinical studies on sex differences in psychostimulant and opioid craving and relapse. Results of the clinical studies reviewed do not appear to support the notion that women are more vulnerable to psychostimulant and opioid craving and relapse. Results of preclinical studies reviewed provide evidence for sex differences in reinstatement and incubation of cocaine seeking but not for reinstatement or incubation of methamphetamine or opioid seeking.
Topics: Analgesics, Opioid; Animals; Cocaine; Cocaine-Related Disorders; Craving; Extinction, Psychological; Female; Humans; Male; Recurrence; Self Administration; Sex Characteristics
PubMed: 34987089
DOI: 10.1124/pharmrev.121.000367