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ACS Pharmacology & Translational Science Jul 2023Methamphetamine exists as two stereoisomers: -(+)-methamphetamine ((+)-MAMP) and -(-)-methamphetamine ((-)-MAMP). The (+)-MAMP stereoisomer is a well-known central... (Review)
Review
Methamphetamine exists as two stereoisomers: -(+)-methamphetamine ((+)-MAMP) and -(-)-methamphetamine ((-)-MAMP). The (+)-MAMP stereoisomer is a well-known central nervous system stimulant, available as a pharmaceutical and clandestine drug of abuse. However, the (-)-MAMP stereoisomer is less well understood despite commercial availability for over 30 years as an over-the-counter (OTC) nasal decongestant in the Vicks Vapor Inhaler (a product of Procter & Gamble). Recently, several generic versions have become available, decreasing the cost and increasing the availability of (-)-MAMP-containing nasal sprays to consumers. Despite widespread commercial availability and use in the United States, a paucity of literature exists on the pharmacology of (-)-MAMP in humans. This knowledge gap is problematic, given the difficulty in separating (-)-MAMP and (+)-MAMP isomers in laboratory assays for workplace drug testing, suspected impaired drivers, post-mortem investigations, and assessment of drug involvement in crimes. In response, this systematic review of the literature coalesces and summarizes available knowledge of (-)-MAMP pharmacology in humans. It was found that available knowledge relies heavily on urine drug and metabolite concentrations, systematic pharmacokinetics studies are lacking, and existing knowledge has been derived from a total of 99 unique participants. The impacts of highlighted gaps in the literature are discussed, focusing on forensic toxicology and law enforcement, and future research directions are suggested.
PubMed: 37470013
DOI: 10.1021/acsptsci.3c00019 -
Nutrients Dec 2023Osteoarthritis (OA) is a degenerative joint disease that is age-related and progressive. It causes the destruction of articular cartilage and underlying bone, often... (Review)
Review
Osteoarthritis (OA) is a degenerative joint disease that is age-related and progressive. It causes the destruction of articular cartilage and underlying bone, often aggravated by inflammatory processes and oxidative stresses. This pathology impairs the quality of life of the elderly, causing pain, reduced mobility, and functional disabilities, especially in obese patients. Phytochemicals with anti-inflammatory and antioxidant activities may be used for long-term treatment of OA, either in combination with current anti-inflammatories and painkillers, or as an alternative to other products such as glucosamine and chondroitin, which improve cartilage structure and elasticity. The current systematic review provides a comprehensive understanding of the use of flavonoids. It highlights chondrocyte, cartilage, and subchondral bone activities, with a particular focus on their nutrigenomic effects. The molecular mechanisms of these molecules demonstrate how they can be used for the prevention and treatment of OA in the elderly population. However, clinical trials are still needed for effective use in clinical practice.
Topics: Aged; Humans; Cartilage, Articular; Flavonoids; Nutrigenomics; Osteoarthritis; Quality of Life
PubMed: 38201942
DOI: 10.3390/nu16010112 -
Viruses Nov 2023Acute hepatitis B infection is associated with severe liver disease and chronic sequelae in some cases. The purpose of this review was to determine the efficacy of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Acute hepatitis B infection is associated with severe liver disease and chronic sequelae in some cases. The purpose of this review was to determine the efficacy of nucleoside analogues (NA) (lamivudine versus entecavir) compared to placebo or no intervention for treating acute primary HBV infection.
METHODS
A meta-analysis for drug intervention was performed, following a fixed-effect model. Randomized controlled trials (RCTs) and quasi-randomized studies that evaluated the outcomes of NA in acute hepatitis B infection were included. The following outcomes were considered: virological cure (PCR negative), elimination of acute infection (seroconversion of HBsAg), mortality, and serious adverse events.
RESULTS
Five trials with 627 adult participants with severe acute hepatitis B defined by biochemical and serologic parameters were included. Virological cure did not favor any intervention: OR 0.96, 95% CI 0.54 to 1.7 ( = 0.90), I2 = 58%. Seroconversion of HBsAg to negative favored placebo/standard-of-care compared to lamivudine: OR 0.54, 95% CI 0.33 to 0.9 ( = 0.02), I2 = 31%. The only trial that compared entecavir and lamivudine favored entecavir over lamivudine (OR: 3.64, 95% CI 1.31-10.13; 90 participants). Adverse events were mild.
CONCLUSION
There is insufficient evidence that NA obtain superior efficacy compared with placebo/standard-of-care in patients with acute viral hepatitis, based on low quality evidence.
Topics: Adult; Humans; Lamivudine; Antiviral Agents; Hepatitis B Surface Antigens; Hepatitis B; Hepatitis B virus; Hepatitis B, Chronic; Treatment Outcome; DNA, Viral
PubMed: 38005918
DOI: 10.3390/v15112241 -
European Journal of Cardio-thoracic... Oct 2023Literature is scarce on the management of patients using direct oral anticoagulants (DOACs) undergoing elective, urgent and emergency surgery. Therefore, we summarize... (Review)
Review
OBJECTIVES
Literature is scarce on the management of patients using direct oral anticoagulants (DOACs) undergoing elective, urgent and emergency surgery. Therefore, we summarize the current evidence and provide literature-based recommendations for the management of patients on DOACs in the perioperative phase.
METHODS
A general literature review was conducted on the pharmacology of DOACs and for recommendations on the management of cardiac surgical patients on DOACs. Additionally, we performed a systematic review for studies on the use of direct DOAC reversal agents in the emergency cardiac surgical setting.
RESULTS
When surgery is elective, the DOAC cessation strategy is relatively straightforward and should be adapted to the renal function. The same approach applies to urgent cases, but additional DOAC activity drug level monitoring tests may be useful. In emergency cases, idarucizumab can be safely administered to patients on dabigatran in any of the perioperative phases. However, andexanet alfa, which is not registered for perioperative use, should not be administered in the preoperative phase to reverse the effect of factor Xa inhibitors, as it may induce temporary heparin resistance. Finally, the administration of (activated) prothrombin complex concentrate may be considered in all patients on DOACs, and such concentrates are generally readily available.
CONCLUSIONS
DOACs offer several advantages over vitamin K antagonists, but care must be taken in patients undergoing cardiac surgery. Although elective and urgent cases can be managed relatively straightforwardly, the management of emergency cases requires particular attention.
Topics: Humans; Administration, Oral; Anticoagulants; Cardiac Surgical Procedures; Dabigatran; Hemorrhage; Heparin
PubMed: 37812245
DOI: 10.1093/ejcts/ezad340 -
Nutrients Dec 2023Withania somnifera (WS), a popular medicinal plant of the Solanaceae family, contains active ingredients with antioxidant, anti-inflammatory, immunomodulatory, and... (Review)
Review
BACKGROUND
Withania somnifera (WS), a popular medicinal plant of the Solanaceae family, contains active ingredients with antioxidant, anti-inflammatory, immunomodulatory, and anti-stress activities. However, its precise mechanisms of action and optimal use as a supplement are not yet fully understood. The objective of this systematic review is to assess the impact of WS supplementation on cortisol levels in stressed humans by analyzing clinical trials conducted prior to May 2023.
METHODS
The assessment was carried out following the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) by exploring the databases of EMBASE, PubMed, Google Scholar, CENTRAL, and Scopus.
RESULTS
Of the 4788 articles identified, only 9 studies met the selection criteria. The selected studies varied in terms of design, results, formulations, dosages, and treatment duration (30-112 days), and involved subjects with varying degrees of stress. WS supplementation decreases cortisol secretion with no significant adverse effects. Nonetheless, none of the studies evaluated the potential impact of cortisol reduction on adrenal function and long-term effects.
CONCLUSIONS
Brief-term supplementation with WS appears to have a stress-reducing effect in stressed individuals. However, since the long-term effects of WS supplementation are not yet fully understood, WS supplements should be used under medical supervision.
Topics: Humans; Plant Extracts; Withania; Hydrocortisone; Plants, Medicinal; Antioxidants
PubMed: 38140274
DOI: 10.3390/nu15245015 -
International Journal of Molecular... Jul 2023Despite recent advances in heart failure (HF) therapy, the risk of cardiovascular (CV) mortality, morbidity, and HF hospitalization (HFH) are major challenges in HF... (Review)
Review
Despite recent advances in heart failure (HF) therapy, the risk of cardiovascular (CV) mortality, morbidity, and HF hospitalization (HFH) are major challenges in HF treatment. We aimed to review the potential of vericiguat as a treatment option for HF. A systematic literature review was performed using the PubMed database and ClinicalTrials.gov. Four randomized controlled trials were identified, which study the safety and efficacy of vericiguat in HF patients. Vericiguat activates soluble guanylate cyclase (sGC) by binding to the beta-subunit, bypassing the requirement for NO-induced activation. The nitric oxide (NO)-sGC-cyclic guanosine monophosphate (cGMP) pathway plays an essential role in cardiovascular (CV) regulation and the protection of healthy cardiac function but is impaired in HF. Vericiguat reduced the risk of CV death and HFH in HF patients with reduced ejection fraction (HFrEF) but showed no therapeutic effect on HF with preserved ejection fraction (HFpEF). The trials demonstrated a favorable safety profile with most common adverse events such as hypotension, syncope, and anemia. Therefore, vericiguat is recommended for patients with HFrEF and a minimum systolic blood pressure of 100 mmHg. Treatment with vericiguat is considered when the individual patient experiences decompensation despite being on guideline-recommended medication, e.g., angiotensin-converting inhibitor/AT1 receptor antagonist, beta-adrenoceptor antagonist, spironolactone, and sodium-glucose transporter 2 inhibitors. Furthermore, larger studies are required to investigate any potential effect of vericiguat in HFpEF patients. Despite the limitations, vericiguat can be recommended for patients with HFrEF, where standard-of-care is insufficient, and the disease worsens.
Topics: Humans; Heart Failure; Treatment Outcome; Stroke Volume; Soluble Guanylyl Cyclase; Cardiotonic Agents; Diuretics
PubMed: 37511587
DOI: 10.3390/ijms241411826 -
Drugs & Aging Nov 2023The acetylcholinesterase inhibitors (AChEIs) donepezil, galantamine, and rivastigmine are commonly used in the management of various forms of dementia. (Meta-Analysis)
Meta-Analysis
BACKGROUND
The acetylcholinesterase inhibitors (AChEIs) donepezil, galantamine, and rivastigmine are commonly used in the management of various forms of dementia.
OBJECTIVES
While these drugs are known to induce classic cholinergic adverse events such as diarrhea, their potential to cause psychiatric adverse events has yet to be thoroughly examined.
METHODS
We sought to determine the risk of psychiatric adverse events associated with the use of AChEIs through a systematic review and meta-analysis of double-blind randomized controlled trials involving patients with Alzheimer's dementia and Parkinson's dementia.
RESULTS
A total of 48 trials encompassing 22,845 patients were included in our analysis. Anorexia was the most commonly reported psychiatric adverse event, followed by agitation, insomnia, and depression. Individuals exposed to AChEIs had a greater risk of experiencing appetite disorders, insomnia, or depression compared with those who received placebo (anorexia: odds ratio [OR] 2.93, 95% confidence interval [CI] 2.29-3.75; p < 0.00001; decreased appetite: OR 1.93, 95% CI 1.33-2.82; p = 0.0006; insomnia: OR 1.55, 95% CI 1.25-1.93; p < 0.0001; and depression: OR 1.59, 95% CI 1.23-2.06, p = 0.0004). Appetite disorders were also more frequent with high-dose versus low-dose therapy. A subgroup analysis revealed that the risk of insomnia was higher for donepezil than for galantamine.
CONCLUSIONS
Our findings suggest that AChEI therapy may negatively impact psychological health, and careful monitoring of new psychiatric symptoms is warranted. Lowering the dose may resolve some psychiatric adverse events, as may switching to galantamine in the case of insomnia.
CLINICAL TRIAL REGISTRATION
The study was pre-registered on PROSPERO (CRD42021258376).
Topics: Humans; Acetylcholinesterase; Alzheimer Disease; Anorexia; Cholinesterase Inhibitors; Donepezil; Galantamine; Parkinson Disease; Phenylcarbamates; Randomized Controlled Trials as Topic; Rivastigmine; Sleep Initiation and Maintenance Disorders
PubMed: 37682445
DOI: 10.1007/s40266-023-01065-x -
Medicine Nov 2023Depression affects millions globally and often coexists with cognitive deficits. This study explored the potential of probiotics in enhancing cognition and ameliorating... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Depression affects millions globally and often coexists with cognitive deficits. This study explored the potential of probiotics in enhancing cognition and ameliorating depressive symptoms in major depressive disorder patients.
METHODS
Utilizing the Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol and the Population, Intervention, Comparator, Outcome, and Study design framework, we systematically reviewed randomized controlled trials examining probiotic effects on cognition and depressive symptoms. Searches spanned 7 databases from January 2010 to May 2022. Risk of bias was assessed using Revised Cochrane Risk of Bias 2.0, and meta-analysis was conducted with RevMan 5.4.1. Publication bias was evaluated via Egger test.
RESULTS
In a systematic review on the effects of probiotic supplementation on cognition and depressive symptoms in depression patients, 635 records were initially identified, with 4 studies ultimately included. These randomized controlled trials were conducted across diverse regions, primarily involving females, with assessment periods ranging from 1 to 2 months. Concerning cognitive outcomes, a statistically significant moderate improvement was found with probiotic supplementation, based on the mean difference and its 95% confidence interval. However, for depressive symptoms, the overall effect was negligible and not statistically significant. A heterogeneity test indicated consistent findings across studies for both cognitive and depressive outcomes (I² = 0% for both). The potential for publication bias was evaluated using the Egger linear regression test, suggesting no significant bias, though caution is advised due to the limited number of studies.
CONCLUSION
Probiotics may enhance cognitive domains and mitigate depressive symptoms, emphasizing the gut-brain axis role. However, methodological variations and brief intervention durations call for more standardized, extensive research.
Topics: Female; Humans; Depressive Disorder, Major; Depression; Probiotics; Cognition; Research Design
PubMed: 38013351
DOI: 10.1097/MD.0000000000036005 -
Frontiers in Endocrinology 2023To assess the alterations in bone mineral density and bone turnover marker concentrations following the administration of denosumab and romosozumab therapies in patients... (Meta-Analysis)
Meta-Analysis
PURPOSE
To assess the alterations in bone mineral density and bone turnover marker concentrations following the administration of denosumab and romosozumab therapies in patients with osteoporosis.
METHODS
PubMed was searched for studies published until January 28, 2023, that investigated the clinical efficacy and bone turnover marker changes of denosumab and romosozumab in the treatment of osteoporosis, with a minimum follow-up of 3 months in each study. Studies were screened, and data on changes in bone mineral density (BMD), P1NP, and TRACP-5b levels after treatment were extracted and included in the analysis.
RESULTS
Six studies were analyzed. At 3 months after treatment, the romosozumab group showed greater changes in lumbar BMD and bone turnover markers. BMD of total hip and femoral neck was relatively delayed. Beginning at 6 to 12 months, romosozumab showed greater changes in bone mineral density and markers of bone turnover.
CONCLUSION
Both romosozumab and denosumab have antiosteoporotic effects, with greater effects on BMD and bone turnover markers observed within 12 months of romosozumab treatment.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero, identifier CRD42023395034.
Topics: Humans; Bone Density; Denosumab; Bone Density Conservation Agents; Osteoporosis
PubMed: 37529613
DOI: 10.3389/fendo.2023.1188969 -
Nutrients Sep 2023Hypertension is the leading preventable risk factor for cardiovascular disease and all-cause mortality worldwide. However, studies have shown increased risk of mortality... (Meta-Analysis)
Meta-Analysis Review
Hypertension is the leading preventable risk factor for cardiovascular disease and all-cause mortality worldwide. However, studies have shown increased risk of mortality from heart disease and stroke even within the normal blood pressure (BP) range, starting at BPs above 110-115/70-75 mm Hg. Nutraceuticals, such as vitamins and minerals, have been studied extensively for their efficacy in lowering BP and may be of benefit to the general, normotensive population in achieving optimal BP. Our study investigated the effects of six nutraceuticals (Vitamins: C, D, E; Minerals: Calcium, Magnesium, Potassium) on both systolic blood pressure (SBP) and diastolic blood pressure (DBP) in this population. We performed a systematic review and pairwise meta-analysis for all six supplements versus placebo. Calcium and magnesium achieved significant reductions in both SBP and DBP of -1.37/-1.63 mm Hg and -2.79/-1.56 mm Hg, respectively. Vitamin E and potassium only yielded significant reductions in SBP with values of -1.76 mm Hg and -2.10 mm Hg, respectively. Vitamins C and D were not found to significantly lower either SBP or DBP. Future studies should determine optimal dosage and treatment length for these supplements in the general, normotensive population.
Topics: Humans; Vitamins; Blood Pressure; Magnesium; Calcium; Dietary Supplements; Hypertension; Minerals; Hypotension; Calcium, Dietary; Potassium; Antihypertensive Agents
PubMed: 37836507
DOI: 10.3390/nu15194223