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Nature Reviews. Disease Primers Mar 2018Systemic arterial hypertension is the most important modifiable risk factor for all-cause morbidity and mortality worldwide and is associated with an increased risk of... (Review)
Review
Systemic arterial hypertension is the most important modifiable risk factor for all-cause morbidity and mortality worldwide and is associated with an increased risk of cardiovascular disease (CVD). Fewer than half of those with hypertension are aware of their condition, and many others are aware but not treated or inadequately treated, although successful treatment of hypertension reduces the global burden of disease and mortality. The aetiology of hypertension involves the complex interplay of environmental and pathophysiological factors that affect multiple systems, as well as genetic predisposition. The evaluation of patients with hypertension includes accurate standardized blood pressure (BP) measurement, assessment of the patients' predicted risk of atherosclerotic CVD and evidence of target-organ damage, and detection of secondary causes of hypertension and presence of comorbidities (such as CVD and kidney disease). Lifestyle changes, including dietary modifications and increased physical activity, are effective in lowering BP and preventing hypertension and its CVD sequelae. Pharmacological therapy is very effective in lowering BP and in preventing CVD outcomes in most patients; first-line antihypertensive medications include angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, dihydropyridine calcium-channel blockers and thiazide diuretics.
Topics: Antihypertensive Agents; Calcium Channel Blockers; Cardiovascular Diseases; Diuretics; Humans; Hypertension; Quality of Life; Renin-Angiotensin System; Sympathetic Nervous System
PubMed: 29565029
DOI: 10.1038/nrdp.2018.14 -
American Journal of Clinical Dermatology Nov 2021Sunscreens have been on the market for many decades as a means of protection against ultraviolet-induced erythema. Over the years, evidence has also shown their efficacy... (Review)
Review
Sunscreens have been on the market for many decades as a means of protection against ultraviolet-induced erythema. Over the years, evidence has also shown their efficacy in the prevention of photoaging, dyspigmentation, DNA damage, and photocarcinogenesis. In the USA, most broad-spectrum sunscreens provide protection against ultraviolet B (UVB) radiation and short-wavelength ultraviolet A (UVA) radiation. Evidence suggests that visible light and infrared light may play a role in photoaging and should be considered when choosing a sunscreen. Currently, there is a paucity of US FDA-approved filters that provide protection against long UVA (> 370 nm) and none against visible light. Additionally, various sunscreen additives such as antioxidants and photolyases have also been reported to protect against and possibly reverse signs of photoaging. This literature review evaluates the utility of sunscreen in protecting against photoaging and further explores the requirements for an ideal sunscreen.
Topics: Drug Approval; Humans; Skin; Skin Aging; Sun Protection Factor; Sunscreening Agents; Ultraviolet Rays; United States; United States Food and Drug Administration
PubMed: 34387824
DOI: 10.1007/s40257-021-00632-5 -
Cell Oct 2019Alzheimer disease (AD) is a heterogeneous disease with a complex pathobiology. The presence of extracellular β-amyloid deposition as neuritic plaques and intracellular... (Review)
Review
Alzheimer disease (AD) is a heterogeneous disease with a complex pathobiology. The presence of extracellular β-amyloid deposition as neuritic plaques and intracellular accumulation of hyperphosphorylated tau as neurofibrillary tangles remains the primary neuropathologic criteria for AD diagnosis. However, a number of recent fundamental discoveries highlight important pathological roles for other critical cellular and molecular processes. Despite this, no disease-modifying treatment currently exists, and numerous phase 3 clinical trials have failed to demonstrate benefits. Here, we review recent advances in our understanding of AD pathobiology and discuss current treatment strategies, highlighting recent clinical trials and opportunities for developing future disease-modifying therapies.
Topics: Alzheimer Disease; Alzheimer Vaccines; Amyloid beta-Peptides; Animals; Apolipoproteins E; Clinical Trials as Topic; Humans; Mice; Plaque, Amyloid; tau Proteins
PubMed: 31564456
DOI: 10.1016/j.cell.2019.09.001 -
International Journal of Molecular... Feb 2022Fragile X syndrome (FXS) is a neurodevelopmental disorder caused by the full mutation as well as highly localized methylation of the fragile X mental retardation 1 ()... (Review)
Review
Fragile X syndrome (FXS) is a neurodevelopmental disorder caused by the full mutation as well as highly localized methylation of the fragile X mental retardation 1 () gene on the long arm of the X chromosome. Children with FXS are commonly co-diagnosed with Autism Spectrum Disorder, attention and learning problems, anxiety, aggressive behavior and sleep disorder, and early interventions have improved many behavior symptoms associated with FXS. In this review, we performed a literature search of original and review articles data of clinical trials and book chapters using MEDLINE (1990-2021) and ClinicalTrials.gov. While we have reviewed the biological importance of the fragile X mental retardation protein (FMRP), the FXS phenotype, and current diagnosis techniques, the emphasis of this review is on clinical interventions. Early non-pharmacological interventions in combination with pharmacotherapy and targeted treatments aiming to reverse dysregulated brain pathways are the mainstream of treatment in FXS. Overall, early diagnosis and interventions are fundamental to achieve optimal clinical outcomes in FXS.
Topics: Animals; Brain; Fragile X Mental Retardation Protein; Fragile X Syndrome; Humans; Phenotype
PubMed: 35216055
DOI: 10.3390/ijms23041935 -
Indian Journal of Dermatology 2020Photosensitive conditions such as melasma and postinflammatory hyperpigmentation (PIH) are exacerbated by exposure to ultraviolet (UV) rays and visible light making... (Review)
Review
Photosensitive conditions such as melasma and postinflammatory hyperpigmentation (PIH) are exacerbated by exposure to ultraviolet (UV) rays and visible light making sunscreen use an essential component of treatment. This is especially true in skin of color patients who are less likely to use photoprotection, even if diagnosed with these photoexacerbated conditions. We aimed to evaluate the body of literature to provide evidence for the use of sunscreen in the treatment of melasma and PIH. We reviewed English articles from PubMed, Journals@Ovid Full Text, and Embase using the search terms "sunscreen" and either "melasma" "PIH," or "post-inflammatory hyperpigmentation." Nine relevant publications provide evidence that a broad spectrum of protection, including UVA, UVB, and visible light within sunscreens can play an adjuvant role in therapy for melasma and PIH by stabilizing and improving these pigmentary disorders in skin of color patients. This review illustrates the advantages and limitations of sunscreen use, as well as practice gaps in photoprotection in the skin of color patients with melasma and PIH.
PubMed: 32029932
DOI: 10.4103/ijd.IJD_295_18 -
Journal of Psychopharmacology (Oxford,... Feb 2021The discovery of the rapid antidepressant effects of the dissociative anaesthetic ketamine, an uncompetitive N-Methyl-D-Aspartate receptor antagonist, is arguably the... (Review)
Review
The discovery of the rapid antidepressant effects of the dissociative anaesthetic ketamine, an uncompetitive N-Methyl-D-Aspartate receptor antagonist, is arguably the most important breakthrough in depression research in the last 50 years. Ketamine remains an off-label treatment for treatment-resistant depression with factors that limit widespread use including its dissociative effects and abuse potential. Ketamine is a racemic mixture, composed of equal amounts of (S)-ketamine and (R)-ketamine. An (S)-ketamine nasal spray has been developed and approved for use in treatment-resistant depression in the United States and Europe; however, some concerns regarding efficacy and side effects remain. Although (R)-ketamine is a less potent N-Methyl-D-Aspartate receptor antagonist than (S)-ketamine, increasing preclinical evidence suggests (R)-ketamine may have more potent and longer lasting antidepressant effects than (S)-ketamine, alongside fewer side effects. Furthermore, a recent pilot trial of (R)-ketamine has demonstrated rapid-acting and sustained antidepressant effects in individuals with treatment-resistant depression. Research is ongoing to determine the specific cellular and molecular mechanisms underlying the antidepressant actions of ketamine and its component enantiomers in an effort to develop future rapid-acting antidepressants that lack undesirable effects. Here, we briefly review findings regarding the antidepressant effects of ketamine and its enantiomers before considering underlying mechanisms including N-Methyl-D-Aspartate receptor antagonism, γ-aminobutyric acid-ergic interneuron inhibition, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic receptor activation, brain-derived neurotrophic factor and tropomyosin kinase B signalling, mammalian target of rapamycin complex 1 and extracellular signal-regulated kinase signalling, inhibition of glycogen synthase kinase-3 and inhibition of lateral habenula bursting, alongside potential roles of the monoaminergic and opioid receptor systems.
Topics: Animals; Antidepressive Agents; Depression; Depressive Disorder, Treatment-Resistant; Humans; Interneurons; Ketamine; Stereoisomerism
PubMed: 33155503
DOI: 10.1177/0269881120959644 -
CNS Drugs Mar 2017Many children and adolescents with attention deficit/hyperactivity disorder (ADHD) are treated with stimulant and non-stimulant medication. ADHD medication may be... (Meta-Analysis)
Meta-Analysis Review
Cardiovascular Effects of Stimulant and Non-Stimulant Medication for Children and Adolescents with ADHD: A Systematic Review and Meta-Analysis of Trials of Methylphenidate, Amphetamines and Atomoxetine.
BACKGROUND
Many children and adolescents with attention deficit/hyperactivity disorder (ADHD) are treated with stimulant and non-stimulant medication. ADHD medication may be associated with cardiovascular effects. It is important to identify whether mean group effects translate into clinically relevant increases for some individual patients, and/or increase the risk for serious cardiovascular adverse events such as stroke or sudden death.
OBJECTIVES
To evaluate potential cardiovascular effects of these treatments, we conducted a systematic review and meta-analysis of the effects of methylphenidate (MPH), amphetamines (AMP), and atomoxetine (ATX) on diastolic and systolic blood pressure (DBP, SBP) and heart rate (HR) in children and adolescents with ADHD.
METHODS
We conducted systematic searches in electronic databases (PsychINFO, EMBASE and Medline) to identify published trials which involved individuals who were (i) diagnosed with ADHD and were aged between 0-18 years; (ii) treated with MPH, AMP or ATX and (iii) had their DBP and SBP and/or HR measured at baseline (pre) and the endpoint (post) of the study treatment. Studies with an open-label design or a double-blind randomised control design of any duration were included. Statistical analysis involved calculating differences between pre- and post-treatment measurements for the various cardiovascular parameters divided by the pooled standard deviation. Further, we assessed the percentage of clinically relevant increased BP or HR, or documented arrhythmias.
RESULTS
Eighteen clinical trials met the inclusion criteria (10 for MPH, 5 for AMP, and 7 for ATX) with data from 5837 participants (80.7% boys) and average duration of 28.7 weeks (range 4-96 weeks). All three medications were associated with a small, but statistically significant pre-post increase of SBP (MPH: standard mean difference [SMD] 0.25, 95% confidence interval [CI] 0.08-0.42, p < 0.01; AMP: SMD 0.09, 95% CI 0.03-0.15, p < 0.01; ATX: SMD 0.16, 95% CI 0.04-0.27, p = 0.01). MPH did not have a pre-post effect on DBP and HR. AMP treatment was associated with a small but statistically significant pre-post increase of DBP (SMD 0.16, CI 0.03-0.29, p = 0.02), as was ATX treatment (SMD 0.22, CI 0.10-0.34, p < 0.01). AMP and ATX were associated with a small to medium statistically significant pre-post increase of HR (AMP: SMD 0.37, CI 0.13-0.60, p < 0.01; ATX: SMD 0.43, CI 0.26-0.60, p < 0.01). The head-to-head comparison of the three medications did not reveal significant differences. Sensitivity analyses revealed that AMP studies of <18 weeks reported higher effect sizes on DBP compared with longer duration studies (F(1) = 19.55, p = 0.05). Further, MPH studies published before 2007 reported higher effect sizes on SBP than studies after 2007 (F(1) = 5.346, p = 0.05). There was no effect of the following moderators: type of medication, doses, sample size, age, gender, type of ADHD, comorbidity or dropout rate. Participants on medication reported 737 (12.6%) other cardiovascular effects. Notably, 2% of patients discontinued their medication treatment due to any cardiovascular effect. However, in the majority of patients, the cardiovascular effects resolved spontaneously, medication doses were changed or the effects were not considered clinically relevant. There were no statistically significant differences between the medication treatments in terms of the severity of cardiovascular effects.
CONCLUSIONS
Statistically significant pre-post increases of SBP, DBP and HR were associated with AMP and ATX treatment in children and adolescents with ADHD, while MPH treatment had a statistically significant effect only on SBP in these patients. These increases may be clinically significant for a significant minority of individuals that experience larger increases. Since increased BP and HR in general are considered risk factors for cardiovascular morbidity and mortality during adult life, paediatric patients using ADHD medication should be monitored closely and regularly for HR and BP.
Topics: Adolescent; Amphetamines; Atomoxetine Hydrochloride; Attention Deficit Disorder with Hyperactivity; Blood Pressure; Central Nervous System Stimulants; Child; Child, Preschool; Clinical Trials as Topic; Heart Rate; Humans; Infant; Methylphenidate; Psychotropic Drugs
PubMed: 28236285
DOI: 10.1007/s40263-017-0410-7 -
The Lancet Regional Health. Europe Mar 2023Observational population studies indicate that prevention of dementia and cognitive decline is being accomplished, possibly as an unintended result of better vascular... (Review)
Review
Observational population studies indicate that prevention of dementia and cognitive decline is being accomplished, possibly as an unintended result of better vascular prevention and healthier lifestyles. Population aging in the coming decades requires deliberate efforts to further decrease its prevalence and societal burden. Increasing evidence supports the efficacy of preventive interventions on persons with intact cognition and high dementia risk. We report recommendations for the deployment of second-generation memory clinics (Brain Health Services) whose mission is evidence-based and ethical dementia prevention in at-risk individuals. The cornerstone interventions consist of (i) assessment of genetic and potentially modifiable risk factors including brain pathology, and risk stratification, (ii) risk communication with ad-hoc protocols, (iii) risk reduction with multi-domain interventions, and (iv) cognitive enhancement with cognitive and physical training. A roadmap is proposed for concept validation and ensuing clinical deployment.
PubMed: 36895446
DOI: 10.1016/j.lanepe.2022.100576 -
Annals of Oncology : Official Journal... Aug 2022Circulating tumour DNA (ctDNA) assays conducted on plasma are rapidly developing a strong evidence base for use in patients with cancer. The European Society for Medical...
Circulating tumour DNA (ctDNA) assays conducted on plasma are rapidly developing a strong evidence base for use in patients with cancer. The European Society for Medical Oncology convened an expert working group to review the analytical and clinical validity and utility of ctDNA assays. For patients with advanced cancer, validated and adequately sensitive ctDNA assays have utility in identifying actionable mutations to direct targeted therapy, and may be used in routine clinical practice, provided the limitations of the assays are taken into account. Tissue-based testing remains the preferred test for many cancer patients, due to limitations of ctDNA assays detecting fusion events and copy number changes, although ctDNA assays may be routinely used when faster results will be clinically important, or when tissue biopsies are not possible or inappropriate. Reflex tumour testing should be considered following a non-informative ctDNA result, due to false-negative results with ctDNA testing. In patients treated for early-stage cancers, detection of molecular residual disease or molecular relapse, has high evidence of clinical validity in anticipating future relapse in many cancers. Molecular residual disease/molecular relapse detection cannot be recommended in routine clinical practice, as currently there is no evidence for clinical utility in directing treatment. Additional potential applications of ctDNA assays, under research development and not recommended for routine practice, include identifying patients not responding to therapy with early dynamic changes in ctDNA levels, monitoring therapy for the development of resistance mutations before clinical progression, and in screening asymptomatic people for cancer. Recommendations for reporting of results, future development of ctDNA assays and future clinical research are made.
Topics: Biomarkers, Tumor; Circulating Tumor DNA; Humans; Mutation; Neoplasm Recurrence, Local; Precision Medicine
PubMed: 35809752
DOI: 10.1016/j.annonc.2022.05.520 -
Journal of Psychopharmacology (Oxford,... May 2018Behavioural and psychological symptoms of dementia (BPSD) include agitation and aggression in people with dementia. BPSD is common on inpatient psychogeriatric units and...
INTRODUCTION
Behavioural and psychological symptoms of dementia (BPSD) include agitation and aggression in people with dementia. BPSD is common on inpatient psychogeriatric units and may prevent individuals from living at home or in residential/nursing home settings. Several drugs and non-pharmacological treatments have been shown to be effective in reducing behavioural and psychological symptoms of dementia. Algorithmic treatment may address the challenge of synthesizing this evidence-based knowledge.
METHODS
A multidisciplinary team created evidence-based algorithms for the treatment of behavioural and psychological symptoms of dementia. We present drug treatment algorithms for agitation and aggression associated with Alzheimer's and mixed Alzheimer's/vascular dementia. Drugs were appraised by psychiatrists based on strength of evidence of efficacy, time to onset of clinical effect, tolerability, ease of use, and efficacy for indications other than behavioural and psychological symptoms of dementia.
RESULTS
After baseline assessment and discontinuation of potentially exacerbating medications, sequential trials are recommended with risperidone, aripiprazole or quetiapine, carbamazepine, citalopram, gabapentin, and prazosin. Titration schedules are proposed, with adjustments for frailty. Additional guidance is given on use of electroconvulsive therapy, optimization of existing cholinesterase inhibitors/memantine, and use of pro re nata medications.
CONCLUSION
This algorithm-based approach for drug treatment of agitation/aggression in Alzheimer's/mixed dementia has been implemented in several Canadian Hospital Inpatient Units. Impact should be assessed in future research.
Topics: Aggression; Algorithms; Alzheimer Disease; Dementia; Drug Administration Schedule; Guidelines as Topic; Humans; Psychomotor Agitation; Psychotropic Drugs
PubMed: 29338602
DOI: 10.1177/0269881117744996