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Experimental Gerontology Apr 2020Nicotinamide adenine dinucleotide (NAD+) is an essential pyridine nucleotide that is present in all living cells. NAD+ acts as an important cofactor and substrate for a...
Nicotinamide adenine dinucleotide (NAD+) is an essential pyridine nucleotide that is present in all living cells. NAD+ acts as an important cofactor and substrate for a multitude of biological processes including energy production, DNA repair, gene expression, calcium-dependent secondary messenger signalling and immunoregulatory roles. The de novo synthesis of NAD+ is primarily dependent on the kynurenine pathway (KP), although NAD+ can also be recycled from nicotinic acid (NA), nicotinamide (NAM) and nicotinamide riboside (NR). NAD+ levels have been reported to decline during ageing and age-related diseases. Recent studies have shown that raising intracellular NAD+ levels represents a promising therapeutic strategy for age-associated degenerative diseases in general and to extend lifespan in small animal models. A systematic review of the literature available on Medline, Embase and Pubmed was undertaken to evaluate the potential health and/or longevity benefits due to increasing NAD+ levels. A total of 1545 articles were identified and 147 articles (113 preclinical and 34 clinical) met criteria for inclusion. Most studies indicated that the NAD+ precursors NAM, NR, nicotinamide mononucleotide (NMN), and to a lesser extent NAD+ and NADH had a favourable outcome on several age-related disorders associated with the accumulation of chronic oxidative stress, inflammation and impaired mitochondrial function. While these compounds presented with a limited acute toxicity profile, evidence is still quite limited and long-term human clinical trials are still nascent in the current literature. Potential risks in raising NAD+ levels in various clinical disorders using NAD+ precursors include the accumulation of putative toxic metabolites, tumorigenesis and promotion of cellular senescence. Therefore, NAD+ metabolism represents a promising target and further studies are needed to recapitulate the preclinical benefits in human clinical trials.
Topics: Aging; Animals; Humans; Inflammation; Mice; NAD; Neurodegenerative Diseases; Niacinamide; Nicotinamide Mononucleotide; Oxidative Stress; Pyridinium Compounds; Rats; Risk Assessment
PubMed: 31917996
DOI: 10.1016/j.exger.2020.110831 -
Brain & Spine 2022Smoking is a major cause of morbidity and mortality worldwide and is responsible for the death of more than 8 million people per year globally. Through a systematic... (Review)
Review
Smoking is a major cause of morbidity and mortality worldwide and is responsible for the death of more than 8 million people per year globally. Through a systematic literature review, we aim to review the harmful effects of tobacco smoking on degenerative spinal diseases (DSD). DSD is a debilitating disease and there is a need to identify if smoking can be an attributable contender for the occurrence of this disease, as it can open up avenues for therapeutic options. Sources such as PubMed and Embase were used to review literature, maintaining tobacco smoking and spinal diseases as inclusion factors, excluding any article that did not explore this relationship. Risk of bias was assessed using analysis of results, sample size and methods and limitations. Upon review of the literature, tobacco smoking was found to be a major risk factor for the occurrence of DSDs, particularly lumbar spinal diseases. Smokers also experienced a greater need for surgery and greater postoperative wound healing complications, increased pain perception, delay in recovery and decreased satisfaction after receiving surgery. These effects were noted along the entire spine. Many mechanisms of action have been identified in the literature that provide plausible pictures of how smoking leads to spinal degeneration, exploring possible primary targets which can open up opportunities to develop potential therapeutic agents. More studies on cervical and thoracic spinal degeneration would be beneficial in identifying the effect of nicotine on these spinal levels. Some limitations included insufficient sample size, inconclusive evidence and lack of sufficient repeat studies. However, there appears to be a sufficient amount of research on smoking directly contributing to lumbar spinal pathology.
PubMed: 36248118
DOI: 10.1016/j.bas.2022.100916 -
International Journal of Environmental... Oct 2021This study investigated the effects of kinesio taping (KT) or KT plus conventional therapy on pain, muscle strength, funrefction, and range of motion in patients with... (Meta-Analysis)
Meta-Analysis Review
This study investigated the effects of kinesio taping (KT) or KT plus conventional therapy on pain, muscle strength, funrefction, and range of motion in patients with knee osteoarthritis (OA). Data sources: Databases included PubMed, Ovid Medline, CINAHL, Airiti Library, EMBASE, and WOS search engines. Search terms related to KT and knee OA were combined and searched. Articles that met the inclusion criteria and were graded with a Jadad score ≥3 were included in a meta-analysis to calculate the total effect. The exclusion criteria were non-English-language articles, non-original articles, non-full-text articles, no description of the intervention, or articles with a Jadad score ≤2. Eleven articles were included in the meta-analysis. KT treatment had a significant small total effect on pain reduction ( < 0.001; = 1509; standardized mean difference (SMD) = -0.42; 95% CI = -0.65 to -0.18) and a significant moderate total effect on isokinetic muscle strength improvement ( = 0.001; = 447; SMD = 0.72; 95% CI = 0.28 to 1.16). No significant total effects of KT on isometric muscle strength, time to complete functional tasks, or ROM improvement were found. KT or KT plus conventional therapy has a significant effect on pain relief and isokinetic but not isometric muscle strength improvement in patients with knee OA. KT can be an effective tool for treating knee OA pain and is especially valuable for aiding in isokinetic muscle strength. (PROSPERO register ID: CRD42021252313).
Topics: Athletic Tape; Humans; Muscle Strength; Osteoarthritis, Knee; Pain; Range of Motion, Articular
PubMed: 34639740
DOI: 10.3390/ijerph181910440 -
Annals of Medicine 2019Fibromyalgia (FM) is a chronic non-degenerative disease, whose nutritional therapy seems controversial. This systematic review aimed to synthesize the knowledge about...
Fibromyalgia (FM) is a chronic non-degenerative disease, whose nutritional therapy seems controversial. This systematic review aimed to synthesize the knowledge about the effect of dietary interventions on patient-reported outcomes (PRO) and inflammation in patients with FM. Six electronic databases - PubMed, BioMed Central, Cochrane library, EMBASE, LILACS and ISI - were searched for clinical trials, in which a dietary intervention in patients with FM diagnosed was conducted. Quality of evidence assessment was measured in accordance with GRADE methodology. Seven clinical trials - 3 randomized controlled trials, 1 unrandomized clinical trial and 3 uncontrolled clinical trials were identified. Dietary approaches included gluten-free diet ( = 1), raw vegetarian diet ( = 2), low Fermentable oligo-, di- and monossacharides, alcohols and polyols (FODMAPs) diet ( = 1), hypocaloric diet ( = 2) and monosodium glutamate- and aspartame-free diet interventions ( = 1). The major PRO were pain and functional repercussion, with 5 out of 7 studies reporting an improvement. The progress in secondary outcomes was reported for fatigue (2/5 studies), sleep quality (2/3 studies), depression and anxiety (3/6 studies), quality of life (4/5 studies), gastrointestinal symptoms (1/2 studies) and inflammatory biomarkers (1/1 study). However, according to Cochrane Risk of Bias, these studies had poor statistical quality. Well-designed studies should be performed to investigate the dietary interventions effect on FM. Key messages Fibromyalgia (FM) is a chronic non-degenerative disease, whose nutritional therapy seems controversial but promising. Pain and functional repercussion in FM patients seem to improve with a hypocaloric diet, a raw vegetarian diet or a low FODMAPs diet, as much as quality of life, quality of sleep, anxiety and depression and inflammatory biomarkers. Existing studies in this subject are scarce and low quality, which does not allow conclusions to be drawn.
Topics: Chronic Disease; Diet, Carbohydrate-Restricted; Diet, Gluten-Free; Diet, Reducing; Fibromyalgia; Humans; Quality of Life
PubMed: 30735059
DOI: 10.1080/07853890.2018.1564360 -
Neuro-Chirurgie Sep 2023Back pain is a very widespread disease pattern and is one of the most frequent causes for consultation of a physician in general. In most cases, discogenic changes are... (Review)
Review
OBJECTIVE
Back pain is a very widespread disease pattern and is one of the most frequent causes for consultation of a physician in general. In most cases, discogenic changes are the pathomorphological correlate of back pain. Numerous risk factors have been identified for these degenerative changes, but the influence and significance of the risk factors remain unclear, which was the aim of this systematic review.
METHODS
A systematic literature search of the commonly used Pubmed database was performed using specific MESH terms. Further selection of the included studies was performed according to the PRISMA scheme, taking into account scientific merit as well as the relation to the research question.
RESULTS
A total of 111 studies out of 1035 found were finally included in the literature search. 134 risk factors for disc degeneration and disc herniation were identified. These were divided into (1) patient-specific risk factors (n░=░34), (2) radiological risk factors (n░=░31), (3) lifestyle risk factors (n░=░6), (4) workplace-related risk factors (n░=░12), (5) genetic risk factors (n░=░50), and (6) other risk factors (n░=░1). Non-adjustable risk factors were age >50 years (OR 1.7/year), female gender (OR 1.41), family disposition (OR 4.0), comorbidities like atherosclerosis (OR 2.24), arthritic changes in other joints (OR 3.1) and history of injuries of the back (OR 3.1). Adjustable factors were elevated BMI (OR 2.77), comorbidities like hypertension (OR 1.25), dyslipidemia (OR 1.26) and diabetes mellitus (OR 6.8), as well as lifestyle habits like smoking (OR 3.8).
DISCUSSION
In summary, intervertebral disc degenerations and herniations represent multifactorial events whose risk factors can be partly influenced and partly not influenced. This systematic review highlights the current state of knowledge as a basis for creating patient-specific algorithms to calculate risk for the development or progression of degenerative disc changes and disc herniations.
Topics: Humans; Female; Middle Aged; Intervertebral Disc Degeneration; Low Back Pain; Intervertebral Disc Displacement; Risk Factors; Life Style; Lumbar Vertebrae
PubMed: 37586480
DOI: 10.1016/j.neuchi.2023.101482 -
Aging and Disease Jun 2023Alzheimer's disease (AD) is a degenerative disease of the central nervous system. The pathogenesis of AD has been explained using cholinergic, β-amyloid toxicity, tau... (Review)
Review
Alzheimer's disease (AD) is a degenerative disease of the central nervous system. The pathogenesis of AD has been explained using cholinergic, β-amyloid toxicity, tau protein hyperphosphorylation, and oxidative stress theories. However, an effective treatment method has not been developed. In recent years, with the discovery of the brain-gut axis (BGA) and breakthroughs made in Parkinson's disease, depression, autism, and other diseases, BGA has become a hotspot in AD research. Several studies have shown that gut microbiota can affect the brain and behavior of patients with AD, especially their cognitive function. Animal models, fecal microbiota transplantation, and probiotic intervention also provide evidence regarding the correlation between gut microbiota and AD. This article discusses the relationship and related mechanisms between gut microbiota and AD based on BGA to provide possible strategies for preventing or alleviating AD symptoms by regulating gut microbiota.
PubMed: 37191418
DOI: 10.14336/AD.2022.1127 -
The Cochrane Database of Systematic... Mar 2022Arthroscopic knee surgery remains a common treatment for symptomatic knee osteoarthritis, including for degenerative meniscal tears, despite guidelines strongly... (Review)
Review
BACKGROUND
Arthroscopic knee surgery remains a common treatment for symptomatic knee osteoarthritis, including for degenerative meniscal tears, despite guidelines strongly recommending against its use. This Cochrane Review is an update of a non-Cochrane systematic review published in 2017.
OBJECTIVES
To assess the benefits and harms of arthroscopic surgery, including debridement, partial menisectomy or both, compared with placebo surgery or non-surgical treatment in people with degenerative knee disease (osteoarthritis, degenerative meniscal tears, or both).
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, and two trials registers up to 16 April 2021, unrestricted by language.
SELECTION CRITERIA
We included randomised controlled trials (RCTs), or trials using quasi-randomised methods of participant allocation, comparing arthroscopic surgery with placebo surgery or non-surgical interventions (e.g. exercise, injections, non-arthroscopic lavage/irrigation, drug therapy, and supplements and complementary therapies) in people with symptomatic degenerative knee disease (osteoarthritis or degenerative meniscal tears or both). Major outcomes were pain, function, participant-reported treatment success, knee-specific quality of life, serious adverse events, total adverse events and knee surgery (replacement or osteotomy).
DATA COLLECTION AND ANALYSIS
Two review authors independently selected studies for inclusion, extracted data, and assessed risk of bias and the certainty of evidence using GRADE. The primary comparison was arthroscopic surgery compared to placebo surgery for outcomes that measured benefits of surgery, but we combined data from all control groups to assess harms and knee surgery (replacement or osteotomy).
MAIN RESULTS
Sixteen trials (2105 participants) met our inclusion criteria. The average age of participants ranged from 46 to 65 years, and 56% of participants were women. Four trials (380 participants) compared arthroscopic surgery to placebo surgery. For the remaining trials, arthroscopic surgery was compared to exercise (eight trials, 1371 participants), a single intra-articular glucocorticoid injection (one trial, 120 participants), non-arthroscopic lavage (one trial, 34 participants), non-steroidal anti-inflammatory drugs (one trial, 80 participants) and weekly hyaluronic acid injections for five weeks (one trial, 120 participants). The majority of trials without a placebo control were susceptible to bias: in particular, selection (56%), performance (75%), detection (75%), attrition (44%) and selective reporting (75%) biases. The placebo-controlled trials were less susceptible to bias and none were at risk of performance or detection bias. Here we limit reporting to the main comparison, arthroscopic surgery versus placebo surgery. High-certainty evidence indicates arthroscopic surgery leads to little or no difference in pain or function at three months after surgery, moderate-certainty evidence indicates there is probably little or no improvement in knee-specific quality of life three months after surgery, and low-certainty evidence indicates arthroscopic surgery may lead to little or no difference in participant-reported success at up to five years, compared with placebo surgery. Mean post-operative pain in the placebo group was 40.1 points on a 0 to 100 scale (where lower score indicates less pain) compared to 35.5 points in the arthroscopic surgery group, a difference of 4.6 points better (95% confidence interval (CI) 0.02 better to 9 better; I = 0%; 4 trials, 309 participants). Mean post-operative function in the placebo group was 75.9 points on a 0 to 100 rating scale (where higher score indicates better function) compared to 76 points in the arthroscopic surgery group, a difference of 0.1 points better (95% CI 3.2 worse to 3.4 better; I = 0%; 3 trials, 302 participants). Mean post-operative knee-specific health-related quality of life in the placebo group was 69.7 points on a 0 to 100 rating scale (where higher score indicates better quality of life) compared with 75.3 points in the arthroscopic surgery group, a difference of 5.6 points better (95% CI 0.36 better to 10.68 better; I = 0%; 2 trials, 188 participants). We downgraded this evidence to moderate certainty as the 95% confidence interval does not rule in or rule out a clinically important change. After surgery, 74 out of 100 people reported treatment success with placebo and 82 out of 100 people reported treatment success with arthroscopic surgery at up to five years (risk ratio (RR) 1.11, 95% CI 0.66 to 1.86; I = 53%; 3 trials, 189 participants). We downgraded this evidence to low certainty due to serious indirectness (diversity in definition and timing of outcome measurement) and serious imprecision (small number of events). We are less certain if the risk of serious or total adverse events increased with arthroscopic surgery compared to placebo or non-surgical interventions. Serious adverse events were reported in 6 out of 100 people in the control groups and 8 out of 100 people in the arthroscopy groups from eight trials (RR 1.35, 95% CI 0.64 to 2.83; I = 47%; 8 trials, 1206 participants). Fifteen out of 100 people reported adverse events with control interventions, and 17 out of 100 people with surgery at up to five years (RR 1.15, 95% CI 0.78 to 1.70; I = 48%; 9 trials, 1326 participants). The certainty of the evidence was low, downgraded twice due to serious imprecision (small number of events) and possible reporting bias (incomplete reporting of outcome across studies). Serious adverse events included death, pulmonary embolism, acute myocardial infarction, deep vein thrombosis and deep infection. Subsequent knee surgery (replacement or high tibial osteotomy) was reported in 2 out of 100 people in the control groups and 4 out of 100 people in the arthroscopy surgery groups at up to five years in four trials (RR 2.63, 95% CI 0.94 to 7.34; I = 11%; 4 trials, 864 participants). The certainty of the evidence was low, downgraded twice due to the small number of events.
AUTHORS' CONCLUSIONS
Arthroscopic surgery provides little or no clinically important benefit in pain or function, probably does not provide clinically important benefits in knee-specific quality of life, and may not improve treatment success compared with a placebo procedure. It may lead to little or no difference, or a slight increase, in serious and total adverse events compared to control, but the evidence is of low certainty. Whether or not arthroscopic surgery results in slightly more subsequent knee surgery (replacement or osteotomy) compared to control remains unresolved.
Topics: Aged; Arthroscopy; Female; Humans; Middle Aged; Osteoarthritis, Knee; Pain Measurement; Pain, Postoperative; Quality of Life
PubMed: 35238404
DOI: 10.1002/14651858.CD014328 -
Frontiers in Psychiatry 2021Comorbidities are seen with obsessive-compulsive disorder (OCD) across the lifespan. Neurodevelopmental comorbidities are common in young children, followed by mood,...
Comorbidities are seen with obsessive-compulsive disorder (OCD) across the lifespan. Neurodevelopmental comorbidities are common in young children, followed by mood, anxiety, and obsessive-compulsive related disorders (OCRDs) in children, adolescents and adults, and neurological and degenerative disorders in the elderly. Understanding comorbidity prevalence and patterns has clinical and research implications. We conducted a systematic review and meta-analysis on comorbidities in OCD across the lifespan, with the objective to, first, estimate age-wise pattern and prevalence of comorbidities with OCD and, second, to examine associations of demographic (age at assessment, gender distribution) and clinical characteristics (age of onset, illness severity) with comorbidities. Four electronic databases (PubMed, EMBASE, SCOPUS, and PsycINFO) were searched using predefined search terms for articles published between 1979 and 2020. Eligible studies, across age, reported original findings on comorbidities and had an OCD sample size of ≥100. We excluded studies that did not use standardised diagnostic assessments, or that excluded patients on the basis of comorbidity. We adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The review protocol has been registered on the International Prospective Register of Systematic Reviews. A comorbidity rate of 69% was found in a pooled sample of more than 15,000 individuals. Mood disorders (major depressive disorder), anxiety disorders (generalised anxiety disorder), neurodevelopmental disorders (NDDs) and OCRDs were the commonest comorbidities. Anxiety disorders prevailed in children, mood disorders in adults, whereas NDDs were similarly prevalent. Higher comorbidity with any psychiatric illness, NDDs, and severe mental disorders was seen in males, vs. females. Illness severity was inversely associated with rates for panic disorder, tic disorders, OCRDs, obsessive compulsive personality disorder, and anorexia nervosa. This systematic review and meta-analysis provides base rates for comorbidities in OCD across the lifespan. This has implications for comprehensive clinical evaluation and management planning. The high variability in comorbidity rates suggests the need for quality, multi-centric, large studies, using prospective designs. Unique Identifier: CRD42020215904.
PubMed: 34858219
DOI: 10.3389/fpsyt.2021.703701 -
BMJ (Clinical Research Ed.) Jun 2015To determine benefits and harms of arthroscopic knee surgery involving partial meniscectomy, debridement, or both for middle aged or older patients with knee pain and... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To determine benefits and harms of arthroscopic knee surgery involving partial meniscectomy, debridement, or both for middle aged or older patients with knee pain and degenerative knee disease.
DESIGN
Systematic review and meta-analysis.
MAIN OUTCOME MEASURES
Pain and physical function.
DATA SOURCES
Systematic searches for benefits and harms were carried out in Medline, Embase, CINAHL, Web of Science, and the Cochrane Central Register of Controlled Trials (CENTRAL) up to August 2014. Only studies published in 2000 or later were included for harms.
ELIGIBILITY CRITERIA FOR SELECTING STUDIES
Randomised controlled trials assessing benefit of arthroscopic surgery involving partial meniscectomy, debridement, or both for patients with or without radiographic signs of osteoarthritis were included. For harms, cohort studies, register based studies, and case series were also allowed.
RESULTS
The search identified nine trials assessing the benefits of knee arthroscopic surgery in middle aged and older patients with knee pain and degenerative knee disease. The main analysis, combining the primary endpoints of the individual trials from three to 24 months postoperatively, showed a small difference in favour of interventions including arthroscopic surgery compared with control treatments for pain (effect size 0.14, 95% confidence interval 0.03 to 0.26). This difference corresponds to a benefit of 2.4 (95% confidence interval 0.4 to 4.3) mm on a 0-100 mm visual analogue scale. When analysed over time of follow-up, interventions including arthroscopy showed a small benefit of 3-5 mm for pain at three and six months but not later up to 24 months. No significant benefit on physical function was found (effect size 0.09, -0.05 to 0.24). Nine studies reporting on harms were identified. Harms included symptomatic deep venous thrombosis (4.13 (95% confidence interval 1.78 to 9.60) events per 1000 procedures), pulmonary embolism, infection, and death.
CONCLUSIONS
The small inconsequential benefit seen from interventions that include arthroscopy for the degenerative knee is limited in time and absent at one to two years after surgery. Knee arthroscopy is associated with harms. Taken together, these findings do not support the practise of arthroscopic surgery for middle aged or older patients with knee pain with or without signs of osteoarthritis.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42014009145.
Topics: Arthroscopy; Humans; Osteoarthritis, Knee; Randomized Controlled Trials as Topic
PubMed: 26080045
DOI: 10.1136/bmj.h2747 -
Journal of Neurology Oct 2021The group of genetic degenerative ataxias shares the same feature of gradual deterioration in balance and coordination. However, no cure is yet available for this group... (Review)
Review
BACKGROUND AND PURPOSE
The group of genetic degenerative ataxias shares the same feature of gradual deterioration in balance and coordination. However, no cure is yet available for this group of disorders, while rehabilitation remains a cornerstone in the current therapy. This review aims to present a summary of the current knowledge of balance and coordination training in patients with inherited degenerative ataxia and to discuss the training effectiveness accordingly.
METHODS
A comprehensive search was performed in 5 electronic databases (i.e., Cochrane Library, PEDro, EMbase, PubMed and MEDLINE) to identify the related publications from January, 1999 to January, 2020. Methodological quality was assessed using the Scottish Intercollegiate Guidelines Network (SIGN) grading system and the PEDro scale.
RESULTS
A total of 33 out of 515 studies met the eligibility criteria, and were categorized and discussed by their training methods including: (1) conventional physical/occupational therapy, (2) virtual reality/videogame-based training, and (3) adapted physical activity. Despite the substantial variation among included studies, most patients achieved significant improvement in the aspect of balance and coordination following individually-tailored rehabilitation programs. The effects of training showed a relative consistency regardless of the functional dependency level on admission.
CONCLUSIONS
Balance and coordination training, especially the conventional physical/occupational therapy, is able to improve the balance and coordinative function of patients with genetic degenerative ataxia, but more high-quality studies are needed to formulate recommendations for clinical practice.
Topics: Ataxia; Exercise; Humans; Physical Therapy Modalities; Postural Balance; Video Games; Virtual Reality
PubMed: 32583055
DOI: 10.1007/s00415-020-09938-6