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Acta Dermatovenerologica Alpina,... Dec 2023The objective of anti-aging medicine is to decelerate the aging process and mitigate its associated effects, such as susceptibility to cancer, diabetes, and... (Review)
Review
The objective of anti-aging medicine is to decelerate the aging process and mitigate its associated effects, such as susceptibility to cancer, diabetes, and cardiovascular and neurodegenerative diseases. This review provides an overview of the latest advancements in this field, considering both pharmaceutical and non-pharmaceutical approaches. Electronic literature search involved three databases: MEDLINE, Cochrane, and Google Scholar, supplemented by other available literature. Strategies for delaying aging and related diseases comprise pharmaceutical interventions and lifestyle choices. It is crucial for these strategies to be substantiated by research-based evidence. Lifestyle options include fasting, fasting-mimicking, and ketogenic diets. Anti-aging drugs and supplements operate through diverse mechanisms. Calorie restriction mimetics include the activator of AMP-activated protein kinase (metformin) and inhibitor of mTOR (rapamycin), alongside rilmenidine, exhibiting both effects. Rosmarinic acid, a natural product, functions through its anti-glycation properties. Age-related protein crosslinks are acknowledged as a causative factor in age-related diseases. Anti-aging medicine is an evolving field with a multitude of drugs and strategies, necessitating further clinical studies and long-term follow-up based on clinical experience and insights gained from delayed adverse events.
Topics: Humans; Aging; Caloric Restriction; Metformin; Sirolimus
PubMed: 38126098
DOI: No ID Found -
EBioMedicine Oct 2023Metformin shows beneficial effects on cardiometabolic health in diabetic individuals. However, the beneficial effects in the general population, especially in...
BACKGROUND
Metformin shows beneficial effects on cardiometabolic health in diabetic individuals. However, the beneficial effects in the general population, especially in non-diabetic individuals are unclear. We aim to estimate the effects of perturbation of seven metformin targets on cardiometabolic health using Mendelian randomization (MR).
METHODS
Genetic variants close to metformin-targeted genes associated with expression of the corresponding genes and glycated haemoglobin (HbA) level were used to proxy therapeutic effects of seven metformin-related drug targets. Eight cardiometabolic phenotypes under metformin trials were selected as outcomes (average N = 466,947). MR estimates representing the weighted average effects of the seven effects of metformin targets on the eight outcomes were generated. One-sample MR was applied to estimate the averaged and target-specific effects in 338,425 non-diabetic individuals in UK Biobank.
FINDINGS
Genetically proxied averaged effects of five metformin targets, equivalent to a 0.62% reduction of HbA level, was associated with 37.8% lower risk of coronary artery disease (CAD) (odds ratio [OR] = 0.62, 95% confidence interval [CI] = 0.46-0.84), lower levels of body mass index (BMI) (β = -0.22, 95% CI = -0.35 to -0.09), systolic blood pressure (SBP) (β = -0.19, 95% CI = -0.28 to -0.09) and diastolic blood pressure (DBP) levels (β = -0.29, 95% CI = -0.39 to -0.19). One-sample MR suggested that the seven metformin targets showed averaged and target-specific beneficial effects on BMI, SBP and DBP in non-diabetic individuals.
INTERPRETATION
This study showed that perturbation of seven metformin targets has beneficial effects on BMI and blood pressure in non-diabetic individuals. Clinical trials are needed to investigate whether similar effects can be achieved with metformin medications.
FUNDING
Funding information is provided in the Acknowledgements.
Topics: Humans; Metformin; Mendelian Randomization Analysis; Risk; Coronary Artery Disease; Genome-Wide Association Study; Diabetes Mellitus; Polymorphism, Single Nucleotide
PubMed: 37734206
DOI: 10.1016/j.ebiom.2023.104803 -
Aging Cell Nov 2023Muscle inflammation and fibrosis underlie disuse-related complications and may contribute to impaired muscle recovery in aging. Cellular senescence is an emerging link... (Randomized Controlled Trial)
Randomized Controlled Trial
Disuse-induced muscle fibrosis, cellular senescence, and senescence-associated secretory phenotype in older adults are alleviated during re-ambulation with metformin pre-treatment.
Muscle inflammation and fibrosis underlie disuse-related complications and may contribute to impaired muscle recovery in aging. Cellular senescence is an emerging link between inflammation, extracellular matrix (ECM) remodeling and poor muscle recovery after disuse. In rodents, metformin has been shown to prevent cellular senescence/senescent associated secretory phenotype (SASP), inflammation, and fibrosis making it a potentially practical therapeutic solution. Thus, the purpose of this study was to determine in older adults if metformin monotherapy during bed rest could reduce muscle fibrosis and cellular senescence/SASP during the re-ambulation period. A two-arm controlled trial was utilized in healthy male and female older adults (n = 20; BMI: <30, age: 60 years+) randomized into either placebo or metformin treatment during a two-week run-in and 5 days of bedrest followed by metformin withdrawal during 7 days of recovery. We found that metformin-treated individuals had less type-I myofiber atrophy during disuse, reduced pro-inflammatory transcriptional profiles, and lower muscle collagen deposition during recovery. Collagen content and myofiber size corresponded to reduced whole muscle cellular senescence and SASP markers. Moreover, metformin treatment reduced primary muscle resident fibro-adipogenic progenitors (FAPs) senescent markers and promoted a shift in fibroblast fate to be less myofibroblast-like. Together, these results suggest that metformin pre-treatment improved ECM remodeling after disuse in older adults by possibly altering cellular senescence and SASP in skeletal muscle and in FAPs.
Topics: Male; Female; Humans; Metformin; Senescence-Associated Secretory Phenotype; Cellular Senescence; Muscle, Skeletal; Inflammation; Walking; Collagen; Fibrosis
PubMed: 37486024
DOI: 10.1111/acel.13936 -
International Dental Journal Nov 2023This is the concluding article in the supplement on the role of mouthwashes in oral care, which summarises the current guidelines across the globe regarding their... (Review)
Review
This is the concluding article in the supplement on the role of mouthwashes in oral care, which summarises the current guidelines across the globe regarding their acceptable adjunctive use for managing caries, gingivitis, and periodontal disease. Based on moderate evidence for clinical effectiveness, most current guidelines suggest fluoride mouthwashes for the management of dental caries, and chlorhexidine for the management of periodontal diseases. However there still appears to be gaps in the literature underpinning these recommendations. Importantly, all evidence supports such mouthwash use "adjunctively," alongside mechanical oral hygiene measures. Other antimicrobial mouthwashes such as essential oils and cetylpyridinium chloride may also be clinically effective against plaque and gingivitis, but there is a current lack of robust evidence of natural mouthwashes to recommend their adjunctive use. The authors of the current review are of the view that mouthwashes may not be of much value in those with good periodontal health or low caries risk. The reasons for this are, the potential i) risks of allergic reactions, ii) dysbiosis of the oral microbiota, iii) emergence of antimicrobial resistance, and iv) deleterious effects on the environment. There is, however, much empirical research needed on mouthwashes, particularly in vivo research derived through clinical trials. Thus, dental practitioners need to keep abreast of the evidence base on the current, and the emerging, over-the-counter mouthwashes, and pay heed to the consensus views emanating from systematic reviews, as well as international guidelines on mouthwashes.
Topics: Humans; Mouthwashes; Dental Caries; Dentists; Professional Role; Chlorhexidine; Gingivitis; Periodontal Diseases; Anti-Infective Agents; Anti-Infective Agents, Local
PubMed: 37867062
DOI: 10.1016/j.identj.2023.08.013 -
JAMA Oct 2023Universal nasal mupirocin plus chlorhexidine gluconate (CHG) bathing in intensive care units (ICUs) prevents methicillin-resistant Staphylococcus aureus (MRSA)... (Comparative Study)
Comparative Study Randomized Controlled Trial
IMPORTANCE
Universal nasal mupirocin plus chlorhexidine gluconate (CHG) bathing in intensive care units (ICUs) prevents methicillin-resistant Staphylococcus aureus (MRSA) infections and all-cause bloodstream infections. Antibiotic resistance to mupirocin has raised questions about whether an antiseptic could be advantageous for ICU decolonization.
OBJECTIVE
To compare the effectiveness of iodophor vs mupirocin for universal ICU nasal decolonization in combination with CHG bathing.
DESIGN, SETTING, AND PARTICIPANTS
Two-group noninferiority, pragmatic, cluster-randomized trial conducted in US community hospitals, all of which used mupirocin-CHG for universal decolonization in ICUs at baseline. Adult ICU patients in 137 randomized hospitals during baseline (May 1, 2015-April 30, 2017) and intervention (November 1, 2017-April 30, 2019) were included.
INTERVENTION
Universal decolonization involving switching to iodophor-CHG (intervention) or continuing mupirocin-CHG (baseline).
MAIN OUTCOMES AND MEASURES
ICU-attributable S aureus clinical cultures (primary outcome), MRSA clinical cultures, and all-cause bloodstream infections were evaluated using proportional hazard models to assess differences from baseline to intervention periods between the strategies. Results were also compared with a 2009-2011 trial of mupirocin-CHG vs no decolonization in the same hospital network. The prespecified noninferiority margin for the primary outcome was 10%.
RESULTS
Among the 801 668 admissions in 233 ICUs, the participants' mean (SD) age was 63.4 (17.2) years, 46.3% were female, and the mean (SD) ICU length of stay was 4.8 (4.7) days. Hazard ratios (HRs) for S aureus clinical isolates in the intervention vs baseline periods were 1.17 for iodophor-CHG (raw rate: 5.0 vs 4.3/1000 ICU-attributable days) and 0.99 for mupirocin-CHG (raw rate: 4.1 vs 4.0/1000 ICU-attributable days) (HR difference in differences significantly lower by 18.4% [95% CI, 10.7%-26.6%] for mupirocin-CHG, P < .001). For MRSA clinical cultures, HRs were 1.13 for iodophor-CHG (raw rate: 2.3 vs 2.1/1000 ICU-attributable days) and 0.99 for mupirocin-CHG (raw rate: 2.0 vs 2.0/1000 ICU-attributable days) (HR difference in differences significantly lower by 14.1% [95% CI, 3.7%-25.5%] for mupirocin-CHG, P = .007). For all-pathogen bloodstream infections, HRs were 1.00 (2.7 vs 2.7/1000) for iodophor-CHG and 1.01 (2.6 vs 2.6/1000) for mupirocin-CHG (nonsignificant HR difference in differences, -0.9% [95% CI, -9.0% to 8.0%]; P = .84). Compared with the 2009-2011 trial, the 30-day relative reduction in hazards in the mupirocin-CHG group relative to no decolonization (2009-2011 trial) were as follows: S aureus clinical cultures (current trial: 48.1% [95% CI, 35.6%-60.1%]; 2009-2011 trial: 58.8% [95% CI, 47.5%-70.7%]) and bloodstream infection rates (current trial: 70.4% [95% CI, 62.9%-77.8%]; 2009-2011 trial: 60.1% [95% CI, 49.1%-70.7%]).
CONCLUSIONS AND RELEVANCE
Nasal iodophor antiseptic did not meet criteria to be considered noninferior to nasal mupirocin antibiotic for the outcome of S aureus clinical cultures in adult ICU patients in the context of daily CHG bathing. In addition, the results were consistent with nasal iodophor being inferior to nasal mupirocin.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT03140423.
Topics: Adult; Aged; Aged, 80 and over; Female; Humans; Male; Middle Aged; Administration, Intranasal; Anti-Bacterial Agents; Anti-Infective Agents; Anti-Infective Agents, Local; Baths; Chlorhexidine; Cross Infection; Intensive Care Units; Iodophors; Methicillin-Resistant Staphylococcus aureus; Mupirocin; Pragmatic Clinical Trials as Topic; Sepsis; Staphylococcal Infections; Staphylococcus aureus; United States
PubMed: 37815567
DOI: 10.1001/jama.2023.17219 -
Indian Journal of Ophthalmology Apr 2024This is a comprehensive review after a thorough literature search in PubMed-indexed journals, incorporating current information on the pathophysiology, clinical... (Review)
Review
This is a comprehensive review after a thorough literature search in PubMed-indexed journals, incorporating current information on the pathophysiology, clinical features, diagnosis, medical and surgical therapy, as well as outcomes of Acanthamoeba keratitis (AK). AK is a significant cause of ocular morbidity, and early diagnosis with timely institution of appropriate therapy is the key to obtaining good outcomes. The varied presentations result in frequent misdiagnosis, and co-infections can increase the morbidity of the disease. The first line of therapy continues to be biguanides and diamidines, with surgery as a last resort.
Topics: Humans; Acanthamoeba Keratitis; Pentamidine; Biguanides
PubMed: 38454853
DOI: 10.4103/IJO.IJO_2627_23 -
Antimicrobial Resistance and Infection... Jun 2023Antiseptic bathing did not reduce central-line (CL) associated bloodstream infection (CLABSI) rates in intensive care units (ICU) according to a recent cluster... (Randomized Controlled Trial)
Randomized Controlled Trial
Central-line associated bloodstream infections in intensive care units before and after implementation of daily antiseptic bathing with chlorhexidine or octenidine: a post-hoc analysis of a cluster-randomised controlled trial.
BACKGROUNDS
Antiseptic bathing did not reduce central-line (CL) associated bloodstream infection (CLABSI) rates in intensive care units (ICU) according to a recent cluster randomised controlled trial (cRCT). However, this analysis did not consider baseline infection rates. Our post-hoc analysis of this cRCT aimed to use a before-after comparison to examine the effect of daily bathing with chlorhexidine, octenidine or water and soap (control) on ICU-attributable CLABSI rates.
METHODS
A post-hoc analysis of a multi-center cRCT was done. ICUs that did not yet perform routine antiseptic bathing were randomly assigned to one of three study groups applying daily bathing with 2% chlorhexidine-impregnated cloths, 0.08% octenidine wash mitts or water and soap (control) for 12 months. Baseline data was assessed 12 months before the intervention started when all ICUs routinely used water and soap. Poisson regression and generalised estimating equation models were applied to identify changes of CLABSI rates per 1000 CL days between intervention and baseline periods in each study group.
RESULTS
The cRCT was conducted in 72 ICUs (24 per study group) including 76,139 patients in the baseline and 76,815 patients in the intervention period. In the chlorhexidine group, incidence density of CLABSI was reduced from 1.48 to 0.90 CLABSI per 1000 CL days comparing baseline versus intervention period (P = 0.0085). No reduction was observed in the octenidine group (1.26 versus 1.47 CLABSI per 1000 CL days, P = 0.8735) and the control group (1.20 versus 1.17, P = 0.3298). Adjusted incidence rate ratios (intervention versus baseline) were 0.63 (95%CI 0.46-0.87, P = 0.0172) in the chlorhexidine, 1.17 (95% CI 0.79-1.72, P = 0.5111) in the octenidine and 0.98 (95% CI 0.60-1.58, P = 0.9190) in the control group. Chlorhexidine bathing reduced CLABSI with gram-positive bacteria, mainly coagulase-negative staphylococci (CoNS).
CONCLUSIONS
In this post-hoc analysis of a cRCT, the application of 2% chlorhexidine-impregnated cloths reduced ICU-attributable CLABSI. This preventive effect of chlorhexidine was restricted to CLABSI caused by gram-positive pathogens (CoNS). In contrast, 0.08% octenidine wash mitts did not reduce CLABSI rates in ICUs. Trial registration Registration number DRKS00010475, registration date August 18, 2016.
Topics: Humans; Chlorhexidine; Anti-Infective Agents, Local; Soaps; Cross Infection; Intensive Care Units; Sepsis
PubMed: 37270604
DOI: 10.1186/s13756-023-01260-w -
Drugs Jul 2023Metformin is used worldwide in the treatment of type 2 diabetes and has been used in the treatment of diabetes in pregnancy since the 1970s. It is highly acceptable to... (Review)
Review
Metformin is used worldwide in the treatment of type 2 diabetes and has been used in the treatment of diabetes in pregnancy since the 1970s. It is highly acceptable to patients due to its ease of administration, cost and adverse effect profile. It is effective in reducing macrosomia, large-for-gestational-age infants and reduces maternal weight gain. Despite its many advantages, metformin has been associated with reductions in foetal size and has been associated with an increase in infants born small-for-gestational-age in certain cohorts. In this article, we review its efficacy, adverse effects and long-term follow-up before, during and after pregnancy for both mother and infant. We also evaluate the other forms of treatment for gestational diabetes, including oral therapies, insulin therapy and emerging treatments.
Topics: Pregnancy; Infant; Female; Humans; Metformin; Hypoglycemic Agents; Diabetes Mellitus, Type 2; Diabetes, Gestational; Insulin
PubMed: 37354354
DOI: 10.1007/s40265-023-01899-0 -
Journal of Diabetes Research 2023This review summarizes the correlation between diabetes mellitus (DM) and gastric cancer (GC) from the perspectives of epidemiology, drug use, and potential mechanisms.... (Review)
Review
This review summarizes the correlation between diabetes mellitus (DM) and gastric cancer (GC) from the perspectives of epidemiology, drug use, and potential mechanisms. The association between DM and GC is inconclusive, and the positive direction of the association reported in most published meta-analyses suggests that DM may be an independent risk factor for GC. Many clinical investigations have shown that people with DM and GC who undergo gastrectomy may have better glycemic control. The potential link between DM and GC may involve the interaction of multiple common risk factors, such as obesity, hyperglycemia and hyperinsulinemia, infection, and the use of metformin. Although and data support that infection status and metformin can influence GC risk in DM patients, there are conflicting results. Patient survival outcomes are influenced by multiple factors, so further research is needed to identify the patients who may benefit.
Topics: Humans; Stomach Neoplasms; Diabetes Mellitus; Risk Factors; Hyperglycemia; Metformin; Helicobacter Infections
PubMed: 38020199
DOI: 10.1155/2023/4388437 -
Endocrine Feb 2024During the last decades, gestational diabetes mellitus (GDM) prevalence has been on the rise. While insulin remains the gold standard treatment for GDM, metformin use... (Review)
Review
During the last decades, gestational diabetes mellitus (GDM) prevalence has been on the rise. While insulin remains the gold standard treatment for GDM, metformin use during pregnancy is controversial. This review aimed to comprehensively assess the available data on the efficacy and safety of metformin during pregnancy, both for the mother and the offspring. Metformin has been validated for maternal efficacy and safety, achieving comparable glycemic control with insulin. Additionally, it reduces maternal weight gain and possibly the occurrence of hypertensive disorders. During the early neonatal period, metformin administration does not increase the risk of congenital anomalies or other major adverse effects, including lower APGAR score at 5 min, neonatal intensive care unit admissions, and respiratory distress syndrome. Several studies have demonstrated a reduction in neonatal hypoglycemia. Metformin has been associated with an increase in preterm births and lower birth weight, although this effect is controversial and depends on the indication for which it was administered. Evidence indicates possible altered fetal programming and predisposition to childhood obesity and metabolic syndrome during adulthood after use of metformin in pregnancy. With critical questions still requiring a final verdict, ongoing research on the field must be conducted.
Topics: Child; Pregnancy; Infant, Newborn; Female; Humans; Adult; Metformin; Hypoglycemic Agents; Pediatric Obesity; Diabetes, Gestational; Insulin; Pregnancy Outcome
PubMed: 37798604
DOI: 10.1007/s12020-023-03550-0