OBJECTIVE: The aim of the current study was to assess the cleaning and smear layer removal efficacy of two different rotary files with or without chemical agents on primary teeth.
METHODS: For the study, 90 extracted primary maxillary incisors without internal or external resorption and with at least two-thirds of complete roots were chosen. Then, based on the kind of instruments used to clean and shape the canals, they were randomly assigned to three experimental groups, each consisting of 30 teeth. Group-I: The canal was instrumented manually with K-files, Group-II: The canal was instrumented with Kedo-S files, Group-III: The canal was instrumented with Kedo-SG Blue files. After the canals were finally instrumented, 2 mL of QMixTM solution was used to irrigate 15 samples from each group. The samples were subsequently allowed to remain in the canals for 90 seconds in order to eliminate the smear layer. After that a stereomicroscope was used to assess the cleaning effectiveness.
RESULTS: With irrigant solution, the highest mean value was found in manual K-files (2.86 ± 0.34), followed by Kedo-S files group (1.34 ± 0.26) and Kedo-SG Blue files (1.28 ± 0.18). Without irrigant solution, the highest mean value was found in manual K-files (2.92 ± 0.22) followed by Kedo-S files group (1.44 ± 0.18) and Kedo-SG Blue files (1.36 ± 0.14). There was a statistically significant difference found at all the three levels.
CONCLUSIONS: On conclusion, the current study\'s findings demonstrated that irrigation solution was significantly more effective in cleaning and removing smear layers from pediatric rotary files than manual K-files.
CONCLUSIONS: The effectiveness of endodontic therapy depends on a successful chemomechanical preparation. The canals are instrumented using either hand files or rotary instruments; there are several irrigation and instrumentation techniques. In order to completely sterilize the canals, chemical agents are utilized for irrigation during instrumentation. Due to their numerous biological, antibacterial, anti-inflammatory, and antioxidant qualities, many natural compounds are also utilized as irrigants. How to cite this article: Abushanan A. Evaluation of the Smear Layer Removal Ability of Various Rotary Files with/without Chemical Agents on Primary Teeth: An In Vitro Study. J Contemp Dent Pract 2024;25(4):354-357.

BACKGROUND: Type 2 diabetes (T2D) represents a remarkable disease burden in Japan, and the cost-effectiveness of pharmacotherapy is an important consideration. In this study, we compared the long-term effects of the type of initial medication, as well as the initial frequency of clinic visits, on the occurrence of T2D-related complications. Additionally, we compared the medical costs associated with each treatment pattern.
METHODS: We analyzed electronic health record data collected from multiple primary care clinics in Japan. Patients were selected based on being primarily prescribed either biguanides (BG) or DPP-4 inhibitors (DPP-4i) during a 3-month baseline period, both of which are commonly used as first-choice medications in Japan. We then followed the onset of T2D-related complications and conducted survival analyses. Additionally, we calculated the accumulated medical costs up to the onset of an event or loss to follow-up, and summarized the annual costs per patient for each treatment pattern.
RESULTS: A total of 416 Japanese patients with T2D who initiated treatment between January 2015 and September 2021 were included. The median follow-up period was 2.69 years. The survival analysis showed that the use of DPP-4is and frequent visits from the beginning of treatment did not offer a benefit in suppressing the onset of complications later on. On the other hand, it was found that the annual medical costs for the group using DPP-4i with frequent visits were about 1.9 times higher than for the group using BGs with less frequent visits.
CONCLUSIONS: The results suggest that for Japanese patients with T2D, the use of BGs along with relatively long follow-up intervals in the beginning of treatment can remarkably reduce medical costs while providing a level of complication suppression equivalent to that of the use of DPP-4is or frequent visits.

UNASSIGNED: Surgical site infections frequently occur after open abdominal surgery. Intraoperative wound irrigation as a preventive measure is a common practice worldwide, although evidence supporting this practice is lacking.
UNASSIGNED: To evaluate the preventive effect of intraoperative wound irrigation with polyhexanide solution.
UNASSIGNED: The Intraoperative Wound Irrigation to Prevent Surgical Site Infection After Laparotomy (IOWISI) trial was a multicenter, 3-armed, randomized clinical trial. Patients and outcome assessors were blinded to the intervention. The clinical trial was conducted in 12 university and general hospitals in Germany from September 2017 to December 2021 with 30-day follow-up. Adult patients undergoing laparotomy were eligible for inclusion. The main exclusion criteria were clean laparoscopic procedures and the inability to provide consent. Of 11 700 screened, 689 were included and 557 completed the trial; 689 were included in the intention-to-treat and safety analysis.
UNASSIGNED: Randomization was performed online (3:3:1 allocation) to polyhexanide 0.04%, saline, or no irrigation (control) of the operative wound before closure.
UNASSIGNED: The primary end point was surgical site infection within 30 postoperative days according to the US Centers for Disease Control and Prevention definition.
UNASSIGNED: Among the 689 patients included, 402 were male and 287 were female. The median (range) age was 65.9 (18.5-94.9) years. Participants were randomized to either wound irrigation with polyhexanide (n = 292), saline (n = 295), or no irrigation (n = 102). The procedures were classified as clean contaminated in 92 cases (8%). The surgical site infection incidence was 11.8% overall (81 of 689), 10.6% in the polyhexanide arm (31 of 292), 12.5% in the saline arm (37 of 295), and 12.8% in the no irrigation arm (13 of 102). Irrigation with polyhexanide was not statistically superior to no irrigation or saline irrigation (hazard ratio [HR], 1.23; 95% CI, 0.64-2.36 vs HR, 1.19; 95% CI, 0.74-1.94; P = .47). The incidence of serious adverse events did not differ among the 3 groups.
UNASSIGNED: In this study, intraoperative wound irrigation with polyhexanide solution did not reduce surgical site infection incidence in clean-contaminated open abdominal surgical procedures compared to saline or no irrigation. More clinical trials are warranted to evaluate the potential benefit in contaminated and septic procedures, including the emergency setting.
UNASSIGNED: drks.de Identifier: DRKS00012251.

OBJECTIVE: To compare topical PHMB (polihexanide) 0.02% (0.2 mg/ml)+ propamidine 0.1% (1 mg/ml) with PHMB 0.08% (0.8 mg/ml)+ placebo (PHMB 0.08%) for Acanthamoeba keratitis (AK) treatment.
METHODS: Prospective, randomized, double-masked, active-controlled, multicenter phase 3 study (ClinicalTrials.gov identifier, NCT03274895).
METHODS: One hundred thirty-five patients treated at 6 European centers.
METHODS: Principal inclusion criteria were 12 years of age or older and in vivo confocal microscopy with clinical findings consistent with AK. Also included were participants with concurrent bacterial keratitis who were using topical steroids and antiviral and antifungal drugs before randomization. Principal exclusion criteria were concurrent herpes or fungal keratitis and use of antiamebic therapy (AAT). Patients were randomized 1:1 using a computer-generated block size of 4. This was a superiority trial having a predefined noninferiority margin. The sample size of 130 participants gave approximately 80% power to detect 20-percentage point superiority for PHMB 0.08% for the primary outcome of the medical cure rate (MCR; without surgery or change of AAT) within 12 months, cure defined by clinical criteria 90 days after discontinuing anti-inflammatory agents and AAT. A prespecified multivariable analysis adjusted for baseline imbalances in risk factors affecting outcomes.
METHODS: The main outcome measure was MCR within 12 months, with secondary outcomes including best-corrected visual acuity and treatment failure rates. Safety outcomes included adverse event rates.
RESULTS: One hundred thirty-five participants were randomized, providing 127 in the full-analysis subset (61 receiving PHMB 0.02%+ propamidine and 66 receiving PHMB 0.08%) and 134 in the safety analysis subset. The adjusted MCR within 12 months was 86.6% (unadjusted, 88.5%) for PHMB 0.02%+ propamidine and 86.7% (unadjusted, 84.9%) for PHMB 0.08%; the noninferiority requirement for PHMB 0.08% was met (adjusted difference, 0.1 percentage points; lower one-sided 95% confidence limit, -8.3 percentage points). Secondary outcomes were similar for both treatments and were not analyzed statistically: median best-corrected visual acuity of 20/20 and an overall treatment failure rate of 17 of 127 patients (13.4%), of whom 8 of 127 patients (6.3%) required therapeutic keratoplasty. No serious drug-related adverse events occurred.
CONCLUSIONS: PHMB 0.08% monotherapy may be as effective (or at worse only 8 percentage points less effective) as dual therapy with PHMB 0.02%+ propamidine (a widely used therapy) with medical cure rates of more than 86%, when used with the trial treatment delivery protocol in populations with AK with similar disease severity.
BACKGROUND: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Women have a high risk of frailty independently of age and menopause state. Diabetes and hypertension increase the risk of frailty and cognitive impairment. Metformin has been employed in post-menopausal women and some reports have shown encouraging effects in terms of attenuated frailty. However, the impact on cognitive performance of a recently introduced extended-release formulation of metformin has never been explored.
We studied consecutive frail hypertensive and diabetic older women presenting at the ASL (local health authority of the Italian Ministry of Health) Avellino, Italy, from June 2021 to August 2022, who were treated or not with extended-release metformin. We included a control group of frail older males with diabetes and hypertension treated with extended-release metformin and a control group of frail older women with diabetes and hypertension treated with regular metformin.
A total of 145 patients successfully completed the study. At the end of the 6-month follow-up, we observed a significantly different cognitive performance compared to baseline in the group of frail women treated with extended-release metformin (p: 0.007). Then, we compared the follow-up groups and we observed significant differences between frail women treated vs. untreated (p: 0.041), between treated frail women and treated frail men (p: 0.016), and between women treated with extended-release metformin vs. women treated with regular metformin (p: 0.048). We confirmed the crucial role of extended-release metformin applying a multivariable logistic analysis to adjust for potential confounders.
We evidenced, for the first time to the best of our knowledge, the favorable effects on cognitive impairment of extended-release metformin in frail women with diabetes and hypertension.

Patient data from the National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB) are used to assess the effect of biguanide administration on rates of lactic acidosis (LA) in hospitalized diabetes mellitus (DM) patients. In this retrospective cohort study (from April 2013 to March 2016), we compare DM inpatients prescribed biguanides to DM inpatients who were not prescribed biguanides to quantify the association between biguanides and incidence of LA. In total, 8,111,848 DM patient records are retrieved from the NDB. Of the 528,768 inpatients prescribed biguanides, 782 develop LA. Of the 1,967,982 inpatients not prescribed biguanides, 1310 develop LA. The rate ratio of inpatients who develop LA and are administered biguanides to those who developed LA without receiving biguanides is 1.44 (95% CI, 1.32-1.58). Incidence rates and rate ratios for both sexes are elevated in the group prescribed biguanides for patients aged 70 years and older, markedly in those 80 years and older: 40.12 and 6.31 (95% CI, 4.75-8.39), respectively, for men and 34.96 and 5.40 (95% CI, 3.91-7.46), respectively, for women. Biguanides should be used conservatively in patients older than 70 years, particularly for those with comorbidities, and with caution in patients 80 years and older.

Metabolic reprogramming in cancer is considered to be one of the most important hallmarks to drive proliferation, angiogenesis, and invasion. AMP-activated protein kinase activation is one of the established mechanisms for metformin\'s anti-cancer actions. However, it has been suggested that metformin may exert antitumoral effects by the modulation of other master regulators of cellular energy. Here, based on structural and physicochemical criteria, we tested the hypothesis that metformin may act as an antagonist of L-arginine metabolism and other related metabolic pathways. First, we created a database containing different L-arginine-related metabolites and biguanides. After that, comparisons of structural and physicochemical properties were performed employing different cheminformatic tools. Finally, we performed molecular docking simulations using AutoDock 4.2 to compare the affinities and binding modes of biguanides and L-arginine-related metabolites against their corresponding targets. Our results showed that biguanides, especially metformin and buformin, exhibited a moderate-to-high similarity to the metabolites belonging to the urea cycle, polyamine metabolism, and creatine biosynthesis. The predicted affinities and binding modes for biguanides displayed good concordance with those obtained for some L-arginine-related metabolites, including L-arginine and creatine. In conclusion, metabolic reprogramming in cancer cells by metformin and biguanides may be also driven by metabolic disruption of L-arginine and structurally related compounds.

Both exercise and pre-meal metformin could lower postprandial glucose and lipid profiles.
To explore whether pre-meal metformin administration is superior to metformin administration with the meal in reducing postprandial lipid and glucose metabolism, and whether its combination with exercise confer superior benefits in metabolic syndrome patients.
In a randomized crossover design, 15 metabolic syndrome patients were assigned to 6 sequences including 3 experimental conditions: metformin administration with a test meal (met-meal), metformin administration 30 min prior to a test meal (pre-meal-met) with or without an exercise bout designed to expend 700 Kcal at 60% VO2 peak performed the evening just before pre-meal-met condition. Only 13 participants (3 males, 10 females; age: 46 ± 9.86, HbA1c: 6.23 ± 0.36) were included in the final analysis.
Postprandial triglyceridemia was unaffected by any condition (all P > .05). However, both pre-meal-met (-7.1%, P = .009) and pre-meal-metx (-8.2%, P = .013) significantly reduced total cholesterol AUC with no significant differences between the two latter condition (P = .616). Similarly, LDL-cholesterol levels were significantly lower during both pre-meal-met (-10.1%, P = .013) and pre-meal-metx (-10.7%, P = .021) compared to met-meal with no difference between latter conditions (P = .822). Plasma glucose AUC was significantly reduced by pre-meal-metx compared to both pre-meal-met (-7.5%, P = .045) and met-meal (-8%, P = .03). Insulin AUC was significantly lower during pre-meal-metx compared to met-meal (-36.4%, P = .044).
Metformin administration 30 minutes prior to meal seems to exert favorable effects on postprandial TC and LDL-Cholesterol levels compared to its administration with meal. Addition of one exercise bout only improved postprandial glycemia and insulinemia.
Pan African clinical trial registry, Identifier PACTR202203690920424.

BACKGROUND: We aimed to clarify the risks of initiating antidiabetic drugs for fractures using a nationwide health insurance claims database (NDBJ).
METHODS: Patients aged ≥ 65 years initiating antidiabetic drugs at the outpatient department were enrolled after a 180-day period without prescribed antidiabetic drugs and followed with during 2012-2018 using NDBJ. The adjusted hazard risks (HRs) of each antidiabetic drug (thiazolidine, alpha-glucosidase inhibitor, dipeptidyl peptidase-4 [DPP-4] inhibitor, sulfonylurea, glinide, and insulin) for fractures compared with biguanide were obtained adjusting for age, gender, polypharmacy, dementia, and the other antidiabetic drugs.
RESULTS: The DPP-4 inhibitor was the most often prescribed antidiabetic drug followed by biguanide with prescribed proportions of 71.7% and 12.9%. A total of 4,304 hip fractures and 9,388 vertebral fractures were identified among the 966,700 outpatient participants. Compared with biguanide, insulin, alpha-glucosidase inhibitor, and DPP-4 inhibitor were related to increased hip fracture risks. Vertebral fracture risk was higher in outpatients prescribed with insulin, thiazolidine, and DPP-4 inhibitor compared with biguanide. Patients prescribed insulin for hip and vertebral fractures\' adjusted HRs were 2.17 (95% CI 1.77-2.66) and 1.45 (95% CI 1.24-1.70), respectively. Those prescribed DPP-4 inhibitor for hip and vertebral fractures\' adjusted HRs were 1.27 (95% CI 1.15-1.40) and 1.20 (95% CI 1.12-1.28), respectively.
CONCLUSIONS: Initiating insulin increased the risk of not only hip fractures but also vertebral fractures. Patients initiating antidiabetic drugs had increased risks of hip and vertebral fractures compared with those initiating biguanide independently for age, gender, polypharmacy, and dementia in the Japanese elderly.

UNASSIGNED: Diabetes mellitus (DM) is associated with immune dysregulation, while sulfonylureas or biguanides have been linked to anti-inflammatory mechanisms. In this study, we aimed to examine the occurrence rate of rheumatoid arthritis (RA) among DM patients and its incidence rate between different treatments.
UNASSIGNED: This cohort study used the Taiwan National Health Insurance Research Database between 1997 and 2013 to evaluate the primary outcomes of the preventive role of sulfonylureas or biguanides in the development of RA. We used the Chi-square test for categorical variables and Cox proportional hazard regression and log-rank test to explore the time for development of RA in DM patients. Logistic regression was adopted to estimate the odds ratio of RA in different dosages of medication exposure.
UNASSIGNED: Our cohort study included 94,141 DM cases. The risk of RA development of non-sulfonylureas/biguanides users among the DM group in each analysis was set as the reference, and the adjusted hazard ratio of RA in DM patients who were using sulfonylureas or biguanides was 0.73 (95% confidence interval 0.60-0.90). Within 1 year before the index date, compared with no-biguanides users, patients with more than 180 days of prescription of biguanides had a significantly lower RA risk. Similarly, the significantly lower risk of RA was still observed in DM patients who had more than 365 days of prescription of sulfonylurea within 2 or 3 years before the index date of first RA visit (all p < 0.05).
UNASSIGNED: Our data suggest that sulfonylureas or biguanides are associated with a lower rate of RA development in patients with DM; the effect of biguanides appeared more rapid than that of sulfonylureas, but the sulfonylureas might have a longer effect on lowering RA development incidence.