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PloS One 2024The recommendation for Chlorhexidine (CHX) as a traditional oral care solution is decreasing, and herbal oral care products are being considered as a potential... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The recommendation for Chlorhexidine (CHX) as a traditional oral care solution is decreasing, and herbal oral care products are being considered as a potential alternative. This network meta-analysis aims to determine if herbal oral care products for oral care in mechanically ventilated patients are superior to CHX and provide direction for future research by comparing the effectiveness of herbal oral care products currently available.
MATERIALS AND METHODS
We searched for English-language published and grey literature sources of randomized clinical trials involving herbal oral care solutions in intensive care unit (ICU) oral care (until September 2023). The primary outcome was the incidence of ventilator-associated pneumonia (VAP); the secondary outcome was the oral microbiota quantity. Data were pooled by pairwise meta-analysis and Bayesian network meta-analysis. The risk of bias was assessed using the Cochrane risk of bias tool, and the certainty of evidence was evaluated using the GRADE framework.
RESULTS
Our network meta-analysis included 29 studies, and the results showed that Chinese herb (OR: 0.39, 95% CI: 0.2-0.75) and Miswak (OR: 0.27, 95% CI: 0.07-0.91) were more effective in reducing VAP incidence than CHX. In terms of reducing bacterial counts, Chinese herb (OR: 0.3, 95% CI: 0.19-0.48) was superior to CHX, and all herbal oral care products, including Persica® (alcoholic extract of S. persica, Achillea millefolium, and Mentha spicata), Matrica® (Chamomile extract), and Listerine® (main components include Menthol, Thymol, and Eucalyptol), were better than saline in all aspects but without significant differences.
CONCLUSION
Based on our network meta-analysis, we have observed that Chinese herbal medicine and Miswak are superior to CHX in reducing the incidence of VAP. However, the safety and feasibility of traditional Chinese herbal medicine require further high-quality research for validation. Simultaneously, Matrica® demonstrates a significant reduction in microbial counts but does not exhibit a significant advantage in lowering the incidence of VAP. This observation aligns with the results of clinical double-blind trials. Therefore, we identify Miswak and Matrica® as promising herbal oral care products with the potential to replace CHX. It is essential to emphasize that our study provides guidance for future research rather than conclusive determinations.
REGISTRATION
PROSPERO no. CRD42023398022.
Topics: Pneumonia, Ventilator-Associated; Humans; Randomized Controlled Trials as Topic; Network Meta-Analysis; Chlorhexidine; Mouthwashes; Bayes Theorem; Intensive Care Units
PubMed: 38848351
DOI: 10.1371/journal.pone.0304583 -
Journal of Diabetes Research 2024We compared the glycaemic and cardiorenal effects of combination therapy involving metformin, pioglitazone, sodium-glucose-linked-cotransporter-2 inhibitor (SGLT2i),...
We compared the glycaemic and cardiorenal effects of combination therapy involving metformin, pioglitazone, sodium-glucose-linked-cotransporter-2 inhibitor (SGLT2i), and glucagon-like peptide-1 receptor agonist (GLP-1RA) versus a more conventional glucocentric treatment approach combining sulphonylureas (SU) and insulin from the point of type 2 diabetes (T2D) diagnosis. We performed a retrospective cohort study using the Global Collaborative Network in TriNetX. We included individuals prescribed metformin, pioglitazone, an SGLT2i, and a GLP-1 RA for at least 1-year duration, within 3 years of a T2D diagnosis, and compared with individuals prescribed insulin and a SU within the same temporal pattern. Individuals were followed up for 3 years. We propensity score-matched (PSM) for 26 variables. A total of 1762 individuals were included in the final analysis ( = 881 per cohort). At 3-years, compared to the insulin/SU group, the metformin/pioglitazone/SGLT2i/GLP-1 RA group had a lower risk of heart failure (HR 0.34, 95% CI 0.13-0.87, = 0.018), acute coronary syndrome (HR 0.29, 95% CI 0.12-0.67, = 0.002), stroke (HR 0.17, 95% CI 0.06-0.49, < 0.001), chronic kidney disease (HR 0.50, 95% CI 0.25-0.99, = 0.042), and hospitalisation (HR 0.59, 95% CI 0.46-0.77, < 0.001). In this real-world study, early, intensive polytherapy, targeting the distinct pathophysiological defects in T2D, is associated with significantly more favourable cardiorenal outcomes, compared to insulin and SU therapy.
Topics: Humans; Diabetes Mellitus, Type 2; Female; Male; Hypoglycemic Agents; Retrospective Studies; Middle Aged; Aged; Drug Therapy, Combination; Metformin; Sulfonylurea Compounds; Sodium-Glucose Transporter 2 Inhibitors; Insulin; Glucagon-Like Peptide-1 Receptor; Pioglitazone; Databases, Factual; Blood Glucose; Treatment Outcome
PubMed: 38846063
DOI: 10.1155/2024/3470654 -
Physiological Reports Jun 2024Regular exercise and antihyperglycemic drugs are front-line treatments for type-2 diabetes and related metabolic disorders. Leading drugs are metformin, sodium-glucose... (Review)
Review
Regular exercise and antihyperglycemic drugs are front-line treatments for type-2 diabetes and related metabolic disorders. Leading drugs are metformin, sodium-glucose cotransporter-2 inhibitors, and glucagon-like peptide 1 receptor agonists. Each class has strong individual efficacy to treat hyperglycemia, yet the combination with exercise can yield varied results, some of which include blunting of expected metabolic benefits. Skeletal muscle insulin resistance contributes to the development of type-2 diabetes while improvements in skeletal muscle insulin signaling are among key adaptations to exercise training. The current review identifies recent advances into the mechanisms, with an emphasis on skeletal muscle, of the interaction between exercise and these common antihyperglycemic drugs. The review is written toward researchers and thus highlights specific gaps in knowledge and considerations for future study directions.
Topics: Humans; Muscle, Skeletal; Hypoglycemic Agents; Exercise; Animals; Diabetes Mellitus, Type 2; Insulin Resistance; Metformin; Sodium-Glucose Transporter 2 Inhibitors
PubMed: 38845596
DOI: 10.14814/phy2.16093 -
BMC Cancer Jun 2024The potential efficacy of metformin in breast cancer (BC) has been hotly discussed but never conclusive. This genetics-based study aimed to evaluate the relationships...
PURPOSE
The potential efficacy of metformin in breast cancer (BC) has been hotly discussed but never conclusive. This genetics-based study aimed to evaluate the relationships between metformin targets and BC risk.
METHODS
Metformin targets from DrugBank and genome-wide association study (GWAS) data from IEU OpenGWAS and FinnGen were used to investigate the breast cancer (BC)-metformin causal link with various Mendelian Randomization (MR) methods (e.g., inverse-variance-weighting). The genetic association between type 2 diabetes (T2D) and the drug target of metformin was also analyzed as a positive control. Sensitivity and pleiotropic tests ensured reliability.
RESULTS
The primary targets of metformin are PRKAB1, ETFDH and GPD1L. We found a causal association between PRKAB1 and T2D (odds ratio [OR] 0.959, P = 0.002), but no causal relationship was observed between metformin targets and overall BC risk (PRKAB1: OR 0.990, P = 0.530; ETFDH: OR 0.986, P = 0.592; GPD1L: OR 1.002, P = 0.806). A noteworthy causal relationship was observed between ETFDH and estrogen receptor (ER)-positive BC (OR 0.867, P = 0.018), and between GPD1L and human epidermal growth factor receptor 2 (HER2)-negative BC (OR 0.966, P = 0.040). Other group analyses did not yield positive results.
CONCLUSION
The star target of metformin, PRKAB1, does not exhibit a substantial causal association with the risk of BC. Conversely, metformin, acting as an inhibitor of ETFDH and GPD1L, may potentially elevate the likelihood of developing ER-positive BC and HER2-negative BC. Consequently, it is not advisable to employ metformin as a standard supplementary therapy for BC patients without T2D.
Topics: Humans; Metformin; Breast Neoplasms; Female; Mendelian Randomization Analysis; Diabetes Mellitus, Type 2; Genome-Wide Association Study; Chemotherapy, Adjuvant; Hypoglycemic Agents; Polymorphism, Single Nucleotide
PubMed: 38844880
DOI: 10.1186/s12885-024-12453-w -
The Journal of Maternal-fetal &... Dec 2024To derive accurate estimates of risk of maternal and neonatal complications in women with gestational diabetes mellitus (GDM) and to investigate the association of the...
AIMS
To derive accurate estimates of risk of maternal and neonatal complications in women with gestational diabetes mellitus (GDM) and to investigate the association of the effect size of these risks on subgroups of GDM managed with dietary modification, metformin and insulin therapy.
METHODS
This was a large retrospective cohort study undertaken at a large maternity unit in the United Kingdom between January 2010 and June 2022. We included singleton pregnancies that booked at our unit at 11-13 weeks' gestation. The rates of maternal and neonatal complications in pregnancies with GDM that were managed by a multidisciplinary team (MDT) in the specialist high-risk clinic were compared to those in non-diabetic pregnancies. We stratified pregnancies with GDM into those that were managed with diet, metformin and insulin to pregnancies without diabetes. Logistic regression analysis was carried out to determine risks of pregnancy complications in pregnancies with GDM and its treatment subgroups. Risks were expressed as absolute risks (AR) and odds ratio (OR) (95% confidence intervals [CI]). Forest plots were used to graphically demonstrate risks.
RESULTS
The study population included 51,211 singleton pregnancies including 2089 (4.1%) with GDM and 49,122 (95.9%) controls without diabetes. In pregnancies with GDM, there were 1247 (59.7%) pregnancies managed with diet, 451 (21.6%) with metformin and 391 (18.7%) who required insulin for maintaining euglycaemia. Pregnancies with GDM had higher maternal age, body mass index (BMI), higher rates of Afro-Caribbean and South Asian racial origin and higher rates of chronic hypertension. In pregnancies with GDM compared to non-diabetic controls, there was an increased rate of preterm delivery, delivery of LGA neonate, polyhydramnios, preeclampsia, need for IOL, elective and emergency CS and PPH whereas the rate of delivery of SGA neonates and likelihood of an unassisted vaginal delivery were lower. In pregnancies with GDM, there is significantly increased risk of maternal and neonatal complications in those that require insulin compared to those that are managed on dietary modification alone.
CONCLUSIONS
There is a linear association between the risk of adverse outcomes and the severity of GDM with those on insulin treatment demonstrating an increased association with complications compared to those that have milder disease requiring only dietary modification.
Topics: Humans; Female; Pregnancy; Diabetes, Gestational; Retrospective Studies; Adult; Hypoglycemic Agents; Metformin; Infant, Newborn; Insulin; Pregnancy Outcome; United Kingdom; Severity of Illness Index; Case-Control Studies
PubMed: 38844413
DOI: 10.1080/14767058.2024.2356031 -
JMIR Research Protocols Jun 2024Chronic pain affects tens of millions of US adults and continues to rise in prevalence. Nonpharmacologic behavioral pain treatments are greatly needed and yet are often...
BACKGROUND
Chronic pain affects tens of millions of US adults and continues to rise in prevalence. Nonpharmacologic behavioral pain treatments are greatly needed and yet are often inaccessible, particularly in settings where medication prescribing is prioritized.
OBJECTIVE
This study aims to test the feasibility of a live-instructor, web-based 1-session pain relief skills class in an underserved and potentially at-risk population: people with chronic pain prescribed methadone or buprenorphine either solely for pain or for comorbid opioid use disorder (OUD).
METHODS
This is a national, prospective, single-arm, uncontrolled feasibility trial. The trial is untethered from medical care; to enhance participants' willingness to join the study, no medical records or drug-monitoring records are accessed. At least 45 participants will be recruited from outpatient pain clinics and from an existing research database of individuals who have chronic pain and are taking methadone or buprenorphine. Patient-reported measures will be collected at 6 time points (baseline, immediately post treatment, 2 weeks, and months 1-3) via a web-based platform, paper, or phone formats to include individuals with limited internet or computer access and low literacy skills. At baseline, participants complete demographic questions and 13 study measures (Treatment Expectations, Body Pain Map, Medication Use, Pain Catastrophizing Scale [PCS], Patient-Reported Outcomes Measurement Information System [PROMIS] Measures, and Opioid Craving Scale). Immediately post treatment, a treatment satisfaction and acceptability measure is administered on a 0 (very dissatisfied) to 10 (completely satisfied) scale, with 3 of these items being the primary outcome (perceived usefulness, participant satisfaction, and likelihood of using the skills). At each remaining time point, the participants complete all study measures minus treatment expectations and satisfaction. Participants who do not have current OUD will be assessed for historical OUD, with presence of OUD (yes or no), and history of OUD (yes or no) reported separately. Feasibility threshold is set as an overall group treatment satisfaction rating of 8 of 10. In-depth qualitative interviews will be conducted with about 10 participants to obtain additional data on patient perceptions, satisfactions, needs, and wants. To assess preliminary efficacy, we will examine changes in pain catastrophizing, pain intensity, pain bothersomeness, sleep disturbance, pain interference, depression, anxiety, physical function, global impression of change, and opioid craving at 1 month post treatment.
RESULTS
This project opened to enrollment in September 2021 and completed the recruitment in October 2023. The data collection was completed in February 2024. Results are expected to be published in late 2024.
CONCLUSIONS
Results from this trial will inform the feasibility and preliminary efficacy of Empowered Relief in this population and will inform the design of a future randomized controlled trial testing web-based Empowered Relief in chronic pain and comorbid OUD.
TRIAL REGISTRATION
ClinicalTrials.gov NCT05057988; https://clinicaltrials.gov/study/NCT05057988.
INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID)
DERR1-10.2196/53784.
Topics: Humans; Buprenorphine; Chronic Pain; Methadone; Feasibility Studies; Prospective Studies; Male; Female; Analgesics, Opioid; Adult; Pain Management; Opiate Substitution Treatment; Internet-Based Intervention; Internet; Opioid-Related Disorders; Middle Aged
PubMed: 38843513
DOI: 10.2196/53784 -
Antimicrobial Resistance and Infection... Jun 2024Although uncommon, infections associated with peripheral intravenous catheters (PIVCs) may be responsible for severe life-threatening complications and increase... (Randomized Controlled Trial)
Randomized Controlled Trial
Insertion site and risk of peripheral intravenous catheter colonization and/or local infection: a post hoc analysis of the CLEAN 3 study including more than 800 catheters.
AIM
Although uncommon, infections associated with peripheral intravenous catheters (PIVCs) may be responsible for severe life-threatening complications and increase healthcare costs. Few data are available on the relationship between PIVC insertion site and risk of infectious complications.
METHODS
We performed a post hoc analysis of the CLEAN 3 database, a randomized 2 × 2 factorial study comparing two skin disinfection procedures (2% chlorhexidine-alcohol or 5% povidone iodine-alcohol) and two types of medical devices (innovative or standard) in 989 adults patients requiring PIVC insertion before admission to a medical ward. Insertion sites were grouped into five areas: hand, wrist, forearm, cubital fossa and upper arm. We evaluated the risk of risk of PIVC colonization (i.e., tip culture eluate in broth showing at least one microorganism in a concentration of at least 1000 Colony Forming Units per mL) and/or local infection (i.e., organisms growing from purulent discharge at PIVC insertion site with no evidence of associated bloodstream infection), and the risk of positive PIVC tip culture (i.e., PIVC-tip culture eluate in broth showing at least one microorganism regardless of its amount) using multivariate Cox models.
RESULTS
Eight hundred twenty three PIVCs with known insertion site and sent to the laboratory for quantitative culture were included. After adjustment for confounding factors, PIVC insertion at the cubital fossa or wrist was associated with increased risk of PIVC colonization and/or local infection (HR [95% CI], 1.64 [0.92-2.93] and 2.11 [1.08-4.13]) and of positive PIVC tip culture (HR [95% CI], 1.49 [1.02-2.18] and 1.59 [0.98-2.59]).
CONCLUSION
PIVC insertion at the wrist or cubital fossa should be avoided whenever possible to reduce the risk of catheter colonization and/or local infection and of positive PIVC tip culture.
Topics: Humans; Female; Male; Catheterization, Peripheral; Catheter-Related Infections; Middle Aged; Aged; Chlorhexidine; Adult; Disinfection; Povidone-Iodine; Risk Factors; Anti-Infective Agents, Local; Equipment Contamination; Wrist
PubMed: 38840171
DOI: 10.1186/s13756-024-01414-4 -
Journal of Pain and Symptom Management Jun 2024Strong opioids are the cornerstone in the treatment of cancer-related pain.
CONTEXT
Strong opioids are the cornerstone in the treatment of cancer-related pain.
OBJECTIVES
This study aims to compare analgesic effectiveness of different strong opioids for the treatment of cancer-related pain.
METHODS
PubMed and Embase were searched for RCTs that compared strong opioids for treatment of cancer-related pain against one another. A network meta-analysis was conducted and the related Surface Under the Cumulative RAnking (SUCRA)-based treatment ranks were calculated. Primary outcome was pain intensity (numerical rating scale (NRS)) and/or the percentage of patients with ≥50% pain reduction, after 1 and 2-4 weeks.
RESULTS
Sixteen RCTs (1813 patients) were included. Methadone showed, with a high certainty of evidence, increased ORs for treatment success at 1 week, compared with morphine, buprenorphine, fentanyl, and oxycodone, range 3.230-36.833. Methadone had the highest likelihood to be the treatment of preference (ToP) (SUCRA 0.9720). For fentanyl, ORs were lower, however significant and with high certainty. After 2-4 weeks, methadone again showed the highest likelihood for ToP, however, with moderate certainty and non-significant ORs. The combination of morphine/methadone, compared with morphine, buprenorphine, fentanyl, hydromorphone, methadone, and oxycodone achieved a treatment effect of mean NRS difference after 2-4 weeks between -1.100 and -1.528 and had the highest likelihood for ToP.
CONCLUSION
The results suggest that methadone possibly deserves further promotion as first-line treatment for the treatment of cancer-related pain.
PubMed: 38838946
DOI: 10.1016/j.jpainsymman.2024.05.022 -
Scientific Reports Jun 2024Lamin A/C gene (LMNA) mutations contribute to severe striated muscle laminopathies, affecting cardiac and skeletal muscles, with limited treatment options. In this...
Lamin A/C gene (LMNA) mutations contribute to severe striated muscle laminopathies, affecting cardiac and skeletal muscles, with limited treatment options. In this study, we delve into the investigations of five distinct LMNA mutations, including three novel variants and two pathogenic variants identified in patients with muscular laminopathy. Our approach employs zebrafish models to comprehensively study these variants. Transgenic zebrafish expressing wild-type LMNA and each mutation undergo extensive morphological profiling, swimming behavior assessments, muscle endurance evaluations, heartbeat measurement, and histopathological analysis of skeletal muscles. Additionally, these models serve as platform for focused drug screening. We explore the transcriptomic landscape through qPCR and RNAseq to unveil altered gene expression profiles in muscle tissues. Larvae of LMNA(L35P), LMNA(E358K), and LMNA(R453W) transgenic fish exhibit reduced swim speed compared to LMNA(WT) measured by DanioVision. All LMNA transgenic adult fish exhibit reduced swim speed compared to LMNA(WT) in T-maze. Moreover, all LMNA transgenic adult fish, except LMNA(E358K), display weaker muscle endurance than LMNA(WT) measured by swimming tunnel. Histochemical staining reveals decreased fiber size in all LMNA mutations transgenic fish, excluding LMNA(WT) fish. Interestingly, LMNA(A539V) and LMNA(E358K) exhibited elevated heartbeats. We recognize potential limitations with transgene overexpression and conducted association calculations to explore its effects on zebrafish phenotypes. Our results suggest lamin A/C overexpression may not directly impact mutant phenotypes, such as impaired swim speed, increased heart rates, or decreased muscle fiber diameter. Utilizing LMNA zebrafish models for drug screening, we identify L-carnitine treatment rescuing muscle endurance in LMNA(L35P) and creatine treatment reversing muscle endurance in LMNA(R453W) zebrafish models. Creatine activates AMPK and mTOR pathways, improving muscle endurance and swim speed in LMNA(R453W) fish. Transcriptomic profiling reveals upstream regulators and affected genes contributing to motor dysfunction, cardiac anomalies, and ion flux dysregulation in LMNA mutant transgenic fish. These findings faithfully mimic clinical manifestations of muscular laminopathies, including dysmorphism, early mortality, decreased fiber size, and muscle dysfunction in zebrafish. Furthermore, our drug screening results suggest L-carnitine and creatine treatments as potential rescuers of muscle endurance in LMNA(L35P) and LMNA(R453W) zebrafish models. Our study offers valuable insights into the future development of potential treatments for LMNA-related muscular laminopathy.
Topics: Animals; Zebrafish; Lamin Type A; Animals, Genetically Modified; Mutation; Muscle, Skeletal; Creatine; Carnitine; Disease Models, Animal; Laminopathies; Swimming; Transcriptome; Humans
PubMed: 38834813
DOI: 10.1038/s41598-024-63711-7