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The British Journal of Dermatology Nov 2022Various treatments for acne vulgaris exist, but little is known about their comparative effectiveness in relation to acne severity. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Various treatments for acne vulgaris exist, but little is known about their comparative effectiveness in relation to acne severity.
OBJECTIVES
To identify best treatments for mild-to-moderate and moderate-to-severe acne, as determined by clinician-assessed morphological features.
METHODS
We undertook a systematic review and network meta-analysis of randomized controlled trials (RCTs) assessing topical pharmacological, oral pharmacological, physical and combined treatments for mild-to-moderate and moderate-to-severe acne, published up to May 2020. Outcomes included percentage change in total lesion count from baseline, treatment discontinuation for any reason, and discontinuation owing to side-effects. Risk of bias was assessed using the Cochrane risk-of-bias tool and bias adjustment models. Effects for treatments with ≥ 50 observations each compared with placebo are reported below.
RESULTS
We included 179 RCTs with approximately 35 000 observations across 49 treatment classes. For mild-to-moderate acne, the most effective options for each treatment type were as follows: topical pharmacological - combined retinoid with benzoyl peroxide (BPO) [mean difference 26·16%, 95% credible interval (CrI) 16·75-35·36%]; physical - chemical peels, e.g. salicylic or mandelic acid (39·70%, 95% CrI 12·54-66·78%) and photochemical therapy (combined blue/red light) (35·36%, 95% CrI 17·75-53·08%). Oral pharmacological treatments (e.g. antibiotics, hormonal contraceptives) did not appear to be effective after bias adjustment. BPO and topical retinoids were less well tolerated than placebo. For moderate-to-severe acne, the most effective options for each treatment type were as follows: topical pharmacological - combined retinoid with lincosamide (clindamycin) (44·43%, 95% CrI 29·20-60·02%); oral pharmacological - isotretinoin of total cumulative dose ≥ 120 mg kg per single course (58·09%, 95% CrI 36·99-79·29%); physical - photodynamic therapy (light therapy enhanced by a photosensitizing chemical) (40·45%, 95% CrI 26·17-54·11%); combined - BPO with topical retinoid and oral tetracycline (43·53%, 95% CrI 29·49-57·70%). Topical retinoids and oral tetracyclines were less well tolerated than placebo. The quality of included RCTs was moderate to very low, with evidence of inconsistency between direct and indirect evidence. Uncertainty in findings was high, in particular for chemical peels, photochemical therapy and photodynamic therapy. However, conclusions were robust to potential bias in the evidence.
CONCLUSIONS
Topical pharmacological treatment combinations, chemical peels and photochemical therapy were most effective for mild-to-moderate acne. Topical pharmacological treatment combinations, oral antibiotics combined with topical pharmacological treatments, oral isotretinoin and photodynamic therapy were most effective for moderate-to-severe acne. Further research is warranted for chemical peels, photochemical therapy and photodynamic therapy for which evidence was more limited. What is already known about this topic? Acne vulgaris is the eighth most common disease globally. Several topical, oral, physical and combined treatments for acne vulgaris exist. Network meta-analysis (NMA) synthesizes direct and indirect evidence and allows simultaneous inference for all treatments forming an evidence network. Previous NMAs have assessed a limited range of treatments for acne vulgaris and have not evaluated effectiveness of treatments for moderate-to-severe acne. What does this study add? For mild-to-moderate acne, topical treatment combinations, chemical peels, and photochemical therapy (combined blue/red light; blue light) are most effective. For moderate-to-severe acne, topical treatment combinations, oral antibiotics combined with topical treatments, oral isotretinoin and photodynamic therapy (light therapy enhanced by a photosensitizing chemical) are most effective. Based on these findings, along with further clinical and cost-effectiveness considerations, National Institute for Health and Care Excellence (NICE) guidance recommends, as first-line treatments, fixed topical treatment combinations for mild-to-moderate acne and fixed topical treatment combinations, or oral tetracyclines combined with topical treatments, for moderate-to-severe acne.
Topics: Humans; Isotretinoin; Network Meta-Analysis; Acne Vulgaris; Anti-Bacterial Agents; Tetracycline
PubMed: 35789996
DOI: 10.1111/bjd.21739 -
Journal of Sleep Research Aug 2021Suboptimal sleep causes cognitive decline and probably accelerates Alzheimer's Disease (AD) progression. Several sleep interventions have been tested in established AD... (Review)
Review
Suboptimal sleep causes cognitive decline and probably accelerates Alzheimer's Disease (AD) progression. Several sleep interventions have been tested in established AD dementia cases. However early intervention is needed in the course of AD at Mild Cognitive Impairment (MCI) or mild dementia stages to help prevent decline and maintain good quality of life. This systematic review aims to summarize evidence on sleep interventions in MCI and mild AD dementia. Seven databases were systematically searched for interventional studies where ≥ 75% of participants met diagnostic criteria for MCI/mild AD dementia, with a control group and validated sleep outcome measures. Studies with a majority of participants diagnosed with Moderate to Severe AD were excluded. After removal of duplicates, 22,133 references were returned in two separate searches (August 2019 and September 2020). 325 full papers were reviewed with 18 retained. Included papers reported 16 separate studies, total sample (n = 1,056), mean age 73.5 years. 13 interventions were represented: Cognitive Behavioural Therapy - Insomnia (CBT-I), A Multi-Component Group Based Therapy, A Structured Limbs Exercise Programme, Aromatherapy, Phase Locked Loop Acoustic Stimulation, Transcranial Stimulation, Suvorexant, Melatonin, Donepezil, Galantamine, Rivastigmine, Tetrahydroaminoacridine and Continuous Positive Airway Pressure (CPAP). Psychotherapeutic approaches utilising adapted CBT-I and a Structured Limbs Exercise Programme each achieved statistically significant improvements in the Pittsburgh Sleep Quality Index with one study reporting co-existent improved actigraphy variables. Suvorexant significantly increased Total Sleep Time and Sleep Efficiency whilst reducing Wake After Sleep Onset time. Transcranial Stimulation enhanced cortical slow oscillations and spindle power during daytime naps. Melatonin significantly reduced sleep latency in two small studies and sleep to wakefulness transitions in a small sample. CPAP demonstrated efficacy in participants with Obstructive Sleep Apnoea. Evidence to support other interventions was limited. Whilst new evidence is emerging, there remains a paucity of evidence for sleep interventions in MCI and mild AD highlighting a pressing need for high quality experimental studies exploring alternative sleep interventions.
Topics: Alzheimer Disease; Cognitive Dysfunction; Humans; Quality of Life; Sleep
PubMed: 33289311
DOI: 10.1111/jsr.13229 -
Ageing Research Reviews Aug 2022Transcranial magnetic stimulation (TMS) is a non-invasive neuromodulation technique. When stimulation is applied over the primary motor cortex and coupled with... (Meta-Analysis)
Meta-Analysis Review
Cortical excitability and plasticity in Alzheimer's disease and mild cognitive impairment: A systematic review and meta-analysis of transcranial magnetic stimulation studies.
BACKGROUND
Transcranial magnetic stimulation (TMS) is a non-invasive neuromodulation technique. When stimulation is applied over the primary motor cortex and coupled with electromyography measures, TMS can probe functions of cortical excitability and plasticity in vivo. The purpose of this meta-analysis is to evaluate the utility of TMS-derived measures for differentiating patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI) from cognitively normal older adults (CN).
METHODS
Databases searched included PubMed, Embase, APA PsycInfo, Medline, and CINAHL Plus from inception to July 2021.
RESULTS
Sixty-one studies with a total of 2728 participants (1454 patients with AD, 163 patients with MCI, and 1111 CN) were included. Patients with AD showed significantly higher cortical excitability, lower cortical inhibition, and impaired cortical plasticity compared to the CN cohorts. Patients with MCI exhibited increased cortical excitability and reduced plasticity compared to the CN cohort. Additionally, lower cognitive performance was significantly associated with higher cortical excitability and lower inhibition. No seizure events due to TMS were reported, and the mild adverse response rate is approximately 3/1000 (i.e., 9/2728).
CONCLUSIONS
Findings of our meta-analysis demonstrate the potential of using TMS-derived cortical excitability and plasticity measures as diagnostic biomarkers and therapeutic targets for AD and MCI.
Topics: Aged; Alzheimer Disease; Cognitive Dysfunction; Cortical Excitability; Humans; Neuronal Plasticity; Transcranial Magnetic Stimulation
PubMed: 35680080
DOI: 10.1016/j.arr.2022.101660 -
Neurobiology of Aging Feb 2020Repetitive transcranial magnetic stimulation (rTMS), a noninvasive brain stimulation technique, has emerged as a promising treatment for mild cognitive impairment (MCI)... (Meta-Analysis)
Meta-Analysis
Repetitive transcranial magnetic stimulation (rTMS), a noninvasive brain stimulation technique, has emerged as a promising treatment for mild cognitive impairment (MCI) and Alzheimer's disease (AD). Currently, however, the effectiveness of this therapy is unclear because of the low statistical power and heterogeneity of previous trials. The purpose of the meta-analysis was to systematically characterize the effectiveness of various combinations of rTMS parameters on different cognitive domains in patients with MCI and AD. Thirteen studies comprising 293 patients with MCI or AD were included in this analysis. Random-effects analysis revealed an overall medium-to-large effect size (0.77) favoring active rTMS over sham rTMS in the improvement of cognitive functions. Subgroup analyses revealed that (1) high-frequency rTMS over the left dorsolateral prefrontal cortex and low-frequency rTMS at the right dorsolateral prefrontal cortex significantly improved memory functions; (2) high-frequency rTMS targeting the right inferior frontal gyrus significantly enhanced executive performance; and (3) the effects of 5-30 consecutive rTMS sessions could last for 4-12 weeks. Potential mechanisms of rTMS effects on cognitive functions are discussed.
Topics: Alzheimer Disease; Cognition; Cognitive Dysfunction; Humans; Memory; Prefrontal Cortex; Transcranial Magnetic Stimulation
PubMed: 31783330
DOI: 10.1016/j.neurobiolaging.2019.08.020 -
International Journal of Environmental... Jul 2022Aging is characterized by changes in the structure and quality of sleep. When the alterations in sleep become substantial, they can generate or accelerate cognitive... (Review)
Review
Aging is characterized by changes in the structure and quality of sleep. When the alterations in sleep become substantial, they can generate or accelerate cognitive decline, even in the absence of overt pathology. In fact, impaired sleep represents one of the earliest symptoms of Alzheimer's disease (AD). This systematic review aimed to analyze the studies on sleep quality in aging, also considering mild cognitive impairment (MCI) and AD. The review process was conducted according to the PRISMA statement. A total of 71 studies were included, and the whole sample had a mean age that ranged from 58.3 to 93.7 years (62.8-93.7 healthy participants and 61.8-86.7 pathological populations). Of these selected studies, 33 adopt subjective measurements, 31 adopt objective measures, and 10 studies used both. Pathological aging showed a worse impoverishment of sleep than older adults, in both subjective and objective measurements. The most common aspect compromised in AD and MCI were REM sleep, sleep efficiency, sleep latency, and sleep duration. These results underline that sleep alterations are associated with cognitive impairment. In conclusion, the frequency and severity of sleep disturbance appear to follow the evolution of cognitive impairment. The overall results of objective measures seem more consistent than those highlighted by subjective measurements.
Topics: Aged; Aged, 80 and over; Aging; Alzheimer Disease; Cognitive Dysfunction; Humans; Middle Aged; Sleep Quality; Sleep Wake Disorders
PubMed: 35886309
DOI: 10.3390/ijerph19148457 -
Age and Ageing Aug 2022Mild cognitive impairment (MCI) is the preclinical and transitional stage between healthy ageing and dementia that may be a potential 'target' for interventions designed... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Mild cognitive impairment (MCI) is the preclinical and transitional stage between healthy ageing and dementia that may be a potential 'target' for interventions designed to delay progression to dementia. In this systematic review and meta-analysis, we assessed the prevalence of MCI worldwide in community-dwelling adults aged 50 years and older.
METHODS
PubMed, Web of Science, Embase and PsycINFO database searches were conducted from their respective inception dates to 1 September 2021. Data on the overall prevalence of MCI were synthesised using random effects models.
RESULTS
A total of 66 articles covering 242,804 participants fulfilled study criteria for inclusion. The overall prevalence of MCI was 15.56% (95%CI: 13.24-18.03%). Prevalence rates of amnestic MCI and non-amnestic MCI were 10.03% (95%CI: 7.98-12.27%) and 8.72% (95%CI: 6.78-10.89%), respectively. The prevalence of MCI increased with age and decreased with education level. Subgroup and meta-regression analyses revealed that region of study site and male gender proportion per sample were significant correlates of MCI prevalence.
CONCLUSION
The global prevalence of MCI among community dwellers is over 15% and is affected by age, gender, education level and region of study sites. Assessment and interventions targeting MCI within at-risk population subgroups should be considered toward the prevention of dementia.
Topics: Aged; Cognitive Dysfunction; Dementia; Disease Progression; Humans; Male; Middle Aged; Prevalence; Risk Factors
PubMed: 35977150
DOI: 10.1093/ageing/afac173 -
Journal of Cachexia, Sarcopenia and... Feb 2023Sarcopenia is a progressive skeletal muscle disorder involving the loss of muscle mass and function, associated with an increased risk of disability and frailty. Though... (Meta-Analysis)
Meta-Analysis Review
Sarcopenia is a progressive skeletal muscle disorder involving the loss of muscle mass and function, associated with an increased risk of disability and frailty. Though its prevalence in dementia has been studied, its occurrence in mild cognitive impairment (MCI) has not been well established. As MCI is often a prelude to dementia, our study aims to investigate the prevalence of MCI among individuals with sarcopenia and to also ascertain whether sarcopenia is independently associated with MCI. The Cochrane Library, PubMed, Ovid, Embase and Web of Science were systematically searched for articles on MCI and/or sarcopenia published from inception to 1 February 2022. We reviewed the available literature on the number of individuals with MCI and/or sarcopenia and calculated odds ratios (ORs) of sarcopenia in MCI and MCI in sarcopenia, respectively. Statistical analyses were performed using the meta package in Stata, Version 12.0. A total of 13 studies and 27 428 patients were included in our analysis. The pooled prevalence of MCI in participants with sarcopenia was 20.5% (95% confidence interval [CI]: 0.140-0.269) in a total sample of 2923 cases with a high level of heterogeneity (P < 0.001; I = 95.4%). The overall prevalence of sarcopenia with MCI was 9.1% (95% CI: 0.047-0.134, P < 0.001; I = 93.0%). For overall ORs, there were 23 364 subjects with a mean age of 73 years; the overall adjusted OR between MCI and sarcopenia was 1.46 (95% CI: 1.31-1.62). Slight heterogeneity in both adjusted ORs (P = 0.46; I = 0%) was noted across the studies. The prevalence of MCI is relatively high in patients with sarcopenia, and sarcopenia may be a risk factor for MCI.
Topics: Humans; Aged; Sarcopenia; Prevalence; Cognitive Dysfunction; Risk Factors; Dementia
PubMed: 36529141
DOI: 10.1002/jcsm.13143 -
Journal of Neurotrauma Jun 2023Studies investigating long-term symptoms and disability after mild traumatic brain injury (mTBI) have yielded mixed results. This systematic review and meta-analysis... (Meta-Analysis)
Meta-Analysis Review
Studies investigating long-term symptoms and disability after mild traumatic brain injury (mTBI) have yielded mixed results. This systematic review and meta-analysis aimed to determine the prevalence of self-reported post-concussion symptoms (PCS) and disability following mTBI. We systematically searched MEDLINE, Embase, CINAHL, CENTRAL, and PsycInfo to identify inception cohort studies of adults with mTBI. Paired reviewers independently extracted data and assessed risk of bias with the Scottish Intercollegiate Guidelines Network criteria. We identified 43 eligible studies for the systematic review; 41 were rated as high risk of bias, primarily due to high attrition (> 20%). Twenty-one studies (49%) were included in the meta-analyses (five studies were narratively synthesized; 17 studies were duplicate reports). At 3-6 months post-injury, the estimated prevalence of PCS from random-effects meta-analyses was 31.3% (95% confidence interval [CI] = 25.4-38.4) using a lenient definition of PCS (2-4 mild severity PCS) and 18.3% (95% CI = 13.6-24.0) using a more stringent definition. The estimated prevalence of disability was 54.0% (95% CI = 49.4-58.6) and 29.6% (95% CI = 27.8-31.5) when defined as Glasgow Outcome Scale-Extended <8 and <7, respectively. The prevalence of symptoms similar to PCS was higher in adults with mTBI versus orthopedic injury (prevalence ratio = 1.57, 95% CI = 1.22-2.02). In a meta-regression, attrition rate was the only study-related factor significantly associated with higher estimated prevalence of PCS. Setting attrition to 0%, the estimated prevalence of PCS (lenient definition) was 16.1%. We conclude that nearly one in three adults who present to an emergency department or trauma center with mTBI report at least mild severity PCS 3-6 months later, but controlling for attrition bias, the true prevalence may be one in six. Studies with representative samples and high retention rates are needed.
Topics: Adult; Humans; Brain Concussion; Post-Concussion Syndrome; Brain Injuries; Cohort Studies; Prevalence
PubMed: 36472218
DOI: 10.1089/neu.2022.0185 -
Neural Regeneration Research Nov 2022Blood exosomes, which are extracellular vesicles secreted by living cells into the circulating blood, are regarded as a relatively noninvasive novel tool for monitoring... (Review)
Review
Blood exosomes, which are extracellular vesicles secreted by living cells into the circulating blood, are regarded as a relatively noninvasive novel tool for monitoring brain physiology and disease states. An increasing number of blood cargo-loaded exosomes are emerging as potential biomarkers for preclinical and clinical Alzheimer's disease. Therefore, we conducted a meta-analysis and systematic review of molecular biomarkers derived from blood exosomes to comprehensively analyze their diagnostic performance in preclinical Alzheimer's disease, mild cognitive impairment, and Alzheimer's disease. We performed a literature search in PubMed, Web of Science, Embase, and Cochrane Library from their inception to August 15, 2020. The research subjects mainly included Alzheimer's disease, mild cognitive impairment, and preclinical Alzheimer's disease. We identified 34 observational studies, of which 15 were included in the quantitative analysis (Newcastle-Ottawa Scale score 5.87 points) and 19 were used in the qualitative analysis. The meta-analysis results showed that core biomarkers including Aβ, P-T181-tau, P-S396-tau, and T-tau were increased in blood neuron-derived exosomes of preclinical Alzheimer's disease, mild cognitive impairment, and Alzheimer's disease patients. Molecules related to additional risk factors that are involved in neuroinflammation (C1q), metabolism disorder (P-S312-IRS-1), neurotrophic deficiency (HGF), vascular injury (VEGF-D), and autophagy-lysosomal system dysfunction (cathepsin D) were also increased. At the gene level, the differential expression of transcription-related factors (REST) and microRNAs (miR-132) also affects RNA splicing, transport, and translation. These pathological changes contribute to neural loss and synaptic dysfunction. The data confirm that the above-mentioned core molecules and additional risk-related factors in blood exosomes can serve as candidate biomarkers for preclinical and clinical Alzheimer's disease. These findings support further development of exosome biomarkers for a clinical blood test for Alzheimer's disease. This meta-analysis was registered at the International Prospective Register of Systematic Reviews (Registration No. CRD4200173498, 28/04/2020).
PubMed: 35535875
DOI: 10.4103/1673-5374.335832 -
Archives of Disease in Childhood. Fetal... Mar 2020To examine if therapeutic hypothermia reduces the composite outcome of death, moderate or severe disability at 18 months or more after mild neonatal encephalopathy (NE). (Meta-Analysis)
Meta-Analysis
OBJECTIVES
To examine if therapeutic hypothermia reduces the composite outcome of death, moderate or severe disability at 18 months or more after mild neonatal encephalopathy (NE).
DATA SOURCE
MEDLINE, Cochrane database, Scopus and ISI Web of Knowledge databases, using 'hypoxic ischaemic encephalopathy', 'newborn' and 'hypothermia', and 'clinical trials' as medical subject headings and terms. Manual search of the reference lists of all eligible articles and major review articles and additional data from the corresponding authors of selected articles.
STUDY SELECTION
Randomised and quasirandomised controlled trials comparing therapeutic hypothermia with usual care.
DATA EXTRACTION
Safety and efficacy data extracted independently by two reviewers and analysed.
RESULTS
We included the data on 117 babies with mild NE inadvertently recruited to five cooling trials (two whole-body cooling and three selective head cooling) of moderate and severe NE, in the meta-analysis. Adverse outcomes occurred in 11/56 (19.6%) of the cooled babies and 12/61 (19.7%) of the usual care babies (risk ratio 1.11 (95% CIs 0.55 to 2.25)).
CONCLUSIONS
Current evidence is insufficient to recommend routine therapeutic hypothermia for babies with mild encephalopathy and significant benefits or harm cannot be excluded.
Topics: Brain Diseases; Developmental Disabilities; Humans; Hypothermia, Induced; Infant, Newborn; Infant, Newborn, Diseases; Randomized Controlled Trials as Topic
PubMed: 30567775
DOI: 10.1136/archdischild-2018-315711