Drug Of First Choice Research Articles

The Association between Transformation Ability and Antimicrobial Resistant Potential in Haemophilus influenzae.

The prevalence of quinolone low-susceptible Haemophilus influenzae has increased in Japan. Low quinolone susceptibility is caused by point mutations in target genes; however, it can also be caused by horizontal gene transfer via natural transformation. In this study, we examined whether this horizontal gene transfer could be associated with resistance to not only quinolones but also other antimicrobial agents. Horizontal transfer ability was quantified using the experimental transfer assay method for low quinolone susceptibility. Further, the association between horizontal transfer ability and resistance to β-lactams, the first-choice drugs for H. influenzae infection, was investigated. The transformation efficiency of 50 clinical isolates varied widely, ranging from 102 to 106 colony forming unit (CFU) of the colonies obtained by horizontal transfer assay. Efficiency was associated with β-lactam resistance caused by ftsI mutations, indicating that strains with high horizontal transfer ability acquired quinolone low-susceptibility as well as β-lactam resistance more easily. Strains with high transformation efficiency increased the transcript level of comA, suggesting that enhanced com operon was associated with a high DNA uptake ability. Overall, this study revealed that the transformation ability of H. influenzae was associated with multiple antimicrobial resistance. Increase in the number of strains with high horizontal transformation ability has raised concerns regarding the rapid spread of antimicrobial-resistant H. influenzae.

Effectiveness of buffered acetylsalicylic acid compared to other drugs in diseases patients in clinical practice: results of the CARDINAL observational retrospective study

Aim. To evaluate the effectiveness of acetylsalicylic acid (ASA) drugs for secondary prevention of atherosclerotic cardiovascular disease (ASCVD) in clinical practice and compare the effectiveness of the Cardiomagnyl with other ASA drugs.Material and methods. This observational, non-interventional, retrospective study included data from electronic medical records of 18199 patients with ASCVD who were divided into 2 following groups: patients who received ASA 75-100 mg (n=9784) and patients who did not receive ASA (n=8325). The prescription rate of ASA, the choice of the first drug, the duration of ASA therapy, the frequency of switching ASA during treatment, and the choice of the second ASA drug when changing therapy were assessed. Due to the heterogeneity of patients in the above groups, to assess the clinical outcomes, propensity score matching was performed and comparable groups were selected to evaluate the effectiveness of ASA drugs 75-100 mg in patients with ASCVD (n= 427) in comparison with patients not receiving ASA (n=427) and to assess the effectiveness of Cardiomagnyl 75 mg (n=1308) in comparison with enterosoluble ASA 100 mg (CRA) (n=1308) taking into account 24 parameters.Results. The average proportion of patients with ASCVD taking ASA drugs was 58%. During treatment, 54% of patients underwent a change in drug therapy from one ASA drug to another. The prescription rate of Cardiomagnyl as a first-choice drug was 33%, and as a second drug when changing therapy — 21%. The duration of Cardiomagnyl therapy was the longest compared to other ASA drugs and amounted to 16,3 months. The incidence of ischemic stroke, myocardial infarction and major adverse cardiovascular events in the group of patients who received ACS 75-100 mg was significantly lower than in patients who did not take ASA drugs and amounted to 4,7% vs 8,7%, 0,9% vs 3,3%, 5,6% vs 11,9%, respectively. Significantly lower incidence of unstable angina (0,8% vs 2,0%), myocardial infarction (1,5% vs 3,9%) and major adverse cardiovascular events (5,4% vs 7,8%) in group of patients who received Cardiomagnyl 75 mg as opposed to enterosoluble ASA.Conclusion. Significant advantages of buffered ASA (Cardiomagnyl) were revealed in comparison with enterosoluble ASA in clinical practice.

Beta Blockers Improve Prognosis When Used Early in Patients with Cardiogenic Shock: An Analysis of the FRENSHOCK Multicenter Prospective Registry.

Beta blockers (BBs) are a cornerstone for patients with heart failure (HF) and ventricular dysfunction. However, their use in patients recovering from a cardiogenic shock (CS) remains a bone of contention, especially regarding whether and when to reintroduce this class of drugs. FRENSHOCK is a prospective multicenter registry including 772 CS patients from 49 centers. Our aim was to compare outcomes (1-month and 1-year all-cause mortality) between CS patients taking and those not taking BBs in three scenarios: (1) at 24 h after CS; (2) patients who did or did not discontinue BBs within 24 h; and (3) patients who did or did not undergo the early introduction of BBs. Among the 693 CS included, at 24 h after the CS event, 95 patients (13.7%) were taking BB, while 598 (86.3%) were not. Between the groups, there were no differences in terms of major comorbidities or initial CS triggers. Patients receiving BBs at 24 h presented a trend toward reduced all-cause mortality both at 1 month (aHR = 0.61, 95% CI 0.34 to 1.1, p = 0.10) and 1 year, which was, in both cases, not significant. Compared with patients who discontinued BBs at 24 h, patients who did not discontinue BBs showed lower 1-month mortality (aHR = 0.43, 95% CI 0.2 to 0.92, p = 0.03) and a trend to lower 1-year mortality. No reduction in outcomes was observed in patients who underwent an early introduction of BB therapy. BBs are drugs of first choice in patients with HF and should also be considered early in patients with CS. In contrast, the discontinuation of BB therapy resulted in increased 1-month all-cause mortality and a trend toward increased 1-year all-cause mortality.

Russian-Belarusian Expert Council “New opportunities in the treatment of patients with multiple sclerosis” (October 1, 2023). Main conclusions of the first meeting

A joint conclusion of the Russian-Belarusian Expert Council “New opportunities in the treatment of patients with multiple sclerosis” on the organization of medical care, diagnosis and treatment of multiple sclerosis (MS) and other autoimmune diseases is presented. 12 neurologists from different medical institutions in Russia and Belarus took part in the work of the Council. In the conclusions of the Council, special attention was paid to two new Russian original drugs, modifying the course of MS. The place of these drugs in the healthcare system of these countries was determined. Sampeginterferon beta-1a itself is an effective and safe drug of first choice (first-line treatment) for relapsing remitting MS. Divozilimab is a highly effective and safe second-line treatment indicated for rapidly progressive and highly active MS, even when substituted for a firstor second-line treatment in relapsing remitting and secondary progressive (with exacerbations) MS. The experts emphasized how promising the use of these drugs is in the complex treatment of MS.

OXA-48-Producing Uropathogenic Escherichia coli Sequence Type 127, the Netherlands, 2015-2022.

During 2015-2022, a genetic cluster of OXA-48-producing uropathogenic Escherichia coli sequence type 127 spread throughout the Netherlands. The 20 isolates we investigated originated mainly from urine, belonged to Clermont phylotype B2, and carried 18 genes encoding putative uropathogenicity factors. The isolates were susceptible to first-choice antimicrobial drugs for urinary tract infections.

Amlodipine and lufenuron as repurposing drugs against Sporothrix brasiliensis.

Sporotrichosis caused by Sporothrix brasiliensis is a globally emerging infectious disease with limited therapeutic options. Thus, we aimed to evaluate the in vitro activity of amlodipine (AML) and lufenuron (LUF) alone and their interaction with itraconazole (ITZ), the first-choice drug against S. brasiliensis. Twenty clinical isolates of S. brasiliensis from two hyperendemic regions were tested through a microdilution assay to evaluate the minimal inhibitory concentration (MIC) and minimal fungicidal concentration (MFC) of AML and LUF. Checkerboard assay was performed with 10 isolates for both drug interactions with ITZ. AML showed inhibitory and fungicidal activity against all isolates included, with MIC values ranging from 32 to 256 µg/mL, and MFC from 64 to 256 µg/mL. However, none of the S. brasiliensis isolates were inhibited by the highest soluble concentration of LUF (MIC >64 µg/mL for all strains). Synergic interaction of AML and LUF with ITZ occurred in 50% and 40% of the isolates tested, without any antagonistic effects. Both repurposing drugs evaluated in our study showed a promising in vitro activity, especially in synergy with ITZ against S. brasiliensis, warranting future in vivo investigations regarding its activity.

Temporal trends of first time antihypertensive treatment among citizens over 75 years - a register-based, cohort study

Abstract Background Hypertension is highly prevalent, particularly among the increasingly large elderly population. There is a need for investigating the use of antihypertensive drugs in elderly patients. Data on clinicians’ first drug of choice, effectiveness, and magnitude of use are sparse, partly due to older patients often being excluded from clinical trials which in turn limits knowledge about their cardiovascular drug safety. Furthermore, drug metabolism and pharmacokinetics are known to differ with increasing age. Purpose To investigate temporal trends for first-line drug choice for first time antihypertensive treatment among elderly patients over 75 years from 2000-2021. Methods Using nationwide registers, we identified all patients over 75 years initiated on either beta blockers (BB), calcium channel blockers (CCB), renin-angiotensin system inhibitors (RASi), thiazides, or a combination between 2000-2021. Patients treated earlier in life with any antihypertensive drug were excluded, as were patients with atrial fibrillation, heart failure, chronic kidney disease, and acute coronary syndrome. Patients were included on the date of their first claimed prescription and temporal trends were reported as proportions per calendar year. We described adherence, change or discontinuation of antihypertensive medication using additionally claimed prescriptions during the first 180 days following study entry. Only patients alive 180 days after initial inclusion contributed to the latter analysis. Results A total of 187,309 patients (median age 80 years [interquartile range (IQR) :77-84], 59.1% female) were eligible for inclusion. The first drug of choice for antihypertensive treatment in patients above 75 years of age has changed markedly between 2000 (BB 12.7%, CCB 22.3%, RASi 11.6%, thiazides 61.3%, and combinations 2.6%) and 2021 (BB 12.9% CCB 28.2%, RASi 48.2%, thiazides 8.0%, and combinations 2.7%), especially for RASi and thiazides (Figure 1). Following the first 180 days, 172,756 patients (median age 80 [IQR:77:84], 59.3% female) were still alive and eligible. Adherence, discontinuation, and shift varied according to first drug of choice. Discontinuation within 180 days was highest among patients initiated on thiazides 19,544 (28.4%) whereas most patients continued the same 1-drug regimen if they started on RASi (64.6%), BB (57.8%), and CCB (59.5%). The highest proportion who had a second drug added within 180 days were patients initiated on CCB (21.1%) and RASi (21.1%) (Figure 2). Conclusion Elderly patients initiated on antihypertensive medication for the first time after the age of 75 is a substantial patient group, and from 2000–2021 a preference for thiazides has largely been replaced by RASi and CCB. It seemed that patients initiated on thiazides were more likely to discontinue or shift shortly afterwards. Further evaluation of thiazides as an equal first drug of choice for hypertension in the elderly could be warranted.

Considerations of Nystatin Roll in Oral Candidiasis Scenario and the COVID-19 Pandemic—A Review

Oral candidiasis is an opportunistic infection usually related to predisposing factors. Oral manifestations in patients affected by COVID-19 have been reported, as the oral mucosa is the gateway to this viral infection. Xerostomia, as well as other oral symptoms, are predisposing factors for the emergence of oral candidiasis after the COVID-19 pandemic. It is a common pathology, but fatal if left untreated. Nystatin (NYS) is the drug of first choice in the treatment of oral candidiasis. Herein, we reviewed the epidemiology of oral candidiasis and its treatments, focusing on the mechanism of action, dosage forms, and NYS efficacy. NYS is an effective drug against oral candidiasis and belongs to Class IV of the biopharmaceutical classification system; however, its low solubility and low permeability may compromise its availability in the oral cavity and, consequently, its pharmacological action. Future perspectives to overcome drug limitations were also addressed and discussed in our review.

Extended-Spectrum β-Lactamases (ESBL): Challenges and Opportunities.

The rise of antimicrobial resistance, particularly from extended-spectrum β-lactamase producing Enterobacteriaceae (ESBL-E), poses a significant global health challenge as it frequently causes the failure of empirical antibiotic therapy, leading to morbidity and mortality. The E. coli- and K. pneumoniae-derived CTX-M genotype is one of the major types of ESBL. Mobile genetic elements (MGEs) are involved in spreading ESBL genes among the bacterial population. Due to the rapidly evolving nature of ESBL-E, there is a lack of specific standard examination methods. Carbapenem has been considered the drug of first choice against ESBL-E. However, carbapenem-sparing strategies and alternative treatment options are needed due to the emergence of carbapenem resistance. In South Asian countries, the irrational use of antibiotics might have played a significant role in aggravating the problem of ESBL-induced AMR. Superbugs showing resistance to last-resort antibiotics carbapenem and colistin have been reported in South Asian regions, indicating a future bleak picture if no urgent action is taken. To counteract the crisis, we need rapid diagnostic tools along with efficient treatment options. Detailed studies on ESBL and the implementation of the One Health approach including systematic surveillance across the public and animal health sectors are strongly recommended. This review provides an overview of the background, associated risk factors, transmission, and therapy of ESBL with a focus on the current situation and future threat in the developing countries of the South Asian region and beyond.

Bidirectional pharmacokinetic drug interactions between olaparib and metformin

ObjectiveOlaparib is a PARP (poly-ADP-ribose polymerase) inhibitor used for maintenance therapy in BRCA-mutated cancers. Metformin is a first-choice drug used in the treatment of type 2 diabetes. Both drugs are commonly co-administered to oncologic patients with add-on type 2 diabetes mellitus. Olaparib is metabolized by the CYP3A4 enzyme, which may be inhibited by metformin through the Pregnane X Receptor. In vitro studies have shown that olaparib inhibits the following metformin transporters: OCT1, MATE1, and MATE2K. The aim of the study was to assess the influence of ‘the perpetrator drug’ on the pharmacokinetic (PK) parameters of ‘the victim drug’ after a single dose. To evaluate the effect, the AUC0→∞ (area under the curve) ratio was determined (the ratio between AUC0→∞ in the presence of the perpetrator and AUC0→∞ without the presence of the perpetrator).MethodsMale Wistar rats were assigned to three groups (eight animals in each group), which were orally administered: metformin and olaparib (IMET+OLA), vehiculum with metformin (IIMET), and vehiculum with olaparib (IIIOLA). Blood samples were collected after 24 h. HPLC was applied to measure the concentrations of olaparib and metformin. The PK parameters were calculated in a non-compartmental model.ResultsMetformin did not affect the olaparib PK parameters. The AUC0→∞ IMET+OLA/IIIOLA ratio was 0.99. Olaparib significantly increased the metformin Cmax (by 177.8%), AUC0→t (by 159.8%), and AUC0→∞ (by 74.1%). The AUC0→∞ IMET+OLA/IIMET ratio was 1.74.ConclusionsA single dose of metformin did not affect the PK parameters of olaparib, nor did it inhibit the olaparib metabolism, but olaparib significantly changed the metformin pharmacokinetics, which may be of clinical importance.

Clinical Trial: Probiotics in Metformin Intolerant Patients with Type 2 Diabetes (ProGasMet)

BackgroundFor decades, metformin has been the drug of first choice in the management of type 2 diabetes. However, approximately 2–13% of patients do not tolerate metformin due to gastrointestinal (GI) side effects. Since metformin influences the gut microbiota, we hypothesized that a multi-strain probiotics supplementation would mitigate the gastrointestinal symptoms associated with metformin usage. Methods and analysisThis randomized, double-blind, placebo-controlled, single-center, cross-over trial (ProGasMet study) assessed the efficacy of a multi-strain probiotic in 37 patients with metformin intolerance. Patients were randomly allocated (1:1) to receive probiotic (PRO-PLA) or placebo (PLA-PRO) at baseline and, after 12 weeks (period 1), they crossed-over to the other treatment arm (period 2). The primary outcome was the reduction of GI adverse events of metformin. Results37 out of 82 eligible patients were enrolled in the final analysis of whom 35 completed the 32 weeks study period and 2 patients resigned at visit 5. Regardless of the treatment arm allocation, while on probiotic supplementation, there was a significant reduction of incidence (for the probiotic period in PRO-PLA/PLA-PRO: P = 0.017/P = 0.054), quantity and severity of nausea (P = 0.016/P = 0.024), frequency (P = 0.009/P = 0.015) and severity (P = 0.019/P = 0.005) of abdominal bloating/pain as well as significant improvement in self-assessed tolerability of metformin (P < 0.01/P = 0.005). Moreover, there was significant reduction of incidence of diarrhea while on probiotic supplementation in PRO-PLA treatment arm (P = 0.036). ConclusionA multi-strain probiotic diminishes the incidence of gastrointestinal adverse effects in patients with type 2 diabetes and metformin intolerance.

Repurposing Metformin for Vascular Disease.

Metformin has been used as an oral anti-hyperglycaemic drug since the late 1950s; however, following the release in 1998 of the findings of the 20-year United Kingdom Prospective Diabetes Study (UKPDS), metformin use rapidly increased and today is the first-choice anti-hyperglycaemic drug for patients with type 2 diabetes (T2D). Metformin is in daily use by an estimated 150 million people worldwide. Historically, the benefits of metformin as an anti-diabetic and cardiovascular-protective drug have been linked to effects in the liver, where it acts to inhibit gluconeogenesis and lipogenesis, as well as reduce insulin resistance and enhance peripheral glucose utilization. However, direct protective effects on the endothelium and effects in the gut prior to metformin absorption are now recognized as important. In the gut, metformin modulates the glucagon-like peptide- 1 (GLP-1) - gut-brain axis and impacts the intestinal microbiota. As the apparent number of putative tissue and cellular targets for metformin has increased, so has the interest in re-purposing metformin to treat other diseases that include polycystic ovary syndrome (PCOS), cancer, neurodegenerative diseases, and COVID-19. Metformin is also being investigated as an anti-ageing drug. Of particular interest is whether metformin provides the same level of vascular protection in individuals other than those with T2D, including obese individuals with metabolic syndrome, or in the setting of vascular thromboinflammation caused by SARS-CoV-2. In this review, we critically evaluate the literature to highlight clinical settings in which metformin might be therapeutically repurposed for the prevention and treatment of vascular disease.

Traditional Chinese medicine for treatment of echinococcosis: a review

Echinococcosis is a zoonotic parasitic disease caused by infection with Echinococcus species. As the drug of first choice for treatment of echinococcosis, albendazole suffers from problems of large doses and remarkable adverse reactions in clinical therapy. Development of novel drugs against echinococcosis is of urgent need. Recently, great advances have been achieved in the research on traditional Chinese medicine for treatment of echinococcosis. This review summarizes the progress of researches on traditional Chinese medicine for treatment of echinococcosis, aiming to provide insights into development of anti-echinococcosis drugs.

Efficacy and Safety of Intravenous Immunoglobulin Treatment in Selected Neurological Diseases-One Centre's Experience Based on the Therapy of 141 Patients.

Intravenous immunoglobulins (IVIg) are the first-choice drugs for the treatment of certain neuroimmune diseases. The aim of this study was to evaluate the efficacy and safety of IVIg in patients with selected nervous system diseases. The study enrolled patients who received IVIg in programmes financed by the National Health Fund in Poland. The status of patients upon inclusion and during treatment was assessed using scales dedicated to specific neurological diseases. The study enrolled 141 patients aged 56.28 ± 14.72 (51.77% female): 21 patients with myasthenia gravis (MG), 65 with chronic inflammatory demyelinating polyneuropathy (CIDP), 30 with Guillain-Barré syndrome (GBS), 12 with neuromyelitis optica spectrum disorder (NMOSD) and 13 patients with autoimmune encephalitis (AE). Neurological improvement was found in 14 (66.66%) MG patients (with a reduction of at least three points on the Quantitative Myasthenia Gravis Score (QMGS) within 14 days from the completion of the cycle), and in 34 (52.3%) GBS patients (with a reduction of at least one point on the Medical Research Council Scale within 14 days from the completion of the cycle). The parameters with the strongest effect on clinical improvement in MG patients were age [OR 1.033, CI 95% [0.09-1.09], p = 0.049] and baseline QMGS [OR 0.505; CI 95% [0.24-0.87], p = 0.038]. In the majority of CIDP patients (27, 97%) and NMOSD patients (6, 50%), neurological stabilisation was observed (without clinical improvement, defined for CIDP patients as an increase of at least two points on the Lovett Scale after three courses of IVIg were administered, and for NMOSD patients as an increase of at least one point on the Medical Research Council Scale and/or a shift of at least 0.3 logMAR after three courses of treatment). Deep-vein thrombosis was only one serious adverse event in the total group of patients treated with IVIg. The use of IVIg in patients with MG and GBS mostly results in neurological improvement, while in patients with NMOSD and CIDP, it mostly results in disease stabilisation. This could indicate the predominant anti-idiotypic antibody activity of IVIg in acute neuroimmune diseases or during exacerbations in chronic autoimmune diseases. The therapy of AE in comorbid neoplastic disease is burdened with an elevated risk of failure for IVIg. The results of our study confirm the improved safety of IVIg for selected neurological diseases.

The Risk of Methylphenidate Pharmacotherapy for Adults with ADHD.

Attention deficit hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders. It was once thought to be a disorder affecting only children, but in those undiagnosed in childhood, symptoms do not disappear with age. There is now a growing recognition of the late diagnosis and treatment of adults with ADHD. The first-line drug in pharmacotherapy is methylphenidate, and information about its adverse effects, when used by adults, has not been as extensively described as in children. The aim of this article was to review the literature describing the risks of methylphenidate therapy for adults with ADHD. A total of 19 articles-15 clinical trials and 4 case reports presenting rare side effects resulting from methylphenidate therapy, such as reversible ischemic stroke, myocardial infarction, and psychotic episodes, were analyzed. The analysis from clinical trials included 3458 adult patients with ADHD and described the most common side effects, psychiatric adverse events, effects of methylphenidate treatment on sleep, laboratory results, body mass, and cardiovascular symptoms. Methylphenidate treatment is well tolerated, with side effects described, according to severity, as mild to moderate. We conclude that pharmacotherapy is not risk-free and methylphenidate, due to its side effects, may not be the first drug of choice for every patient.

The Direct Effects of Norepinephrine Administration on Pressure Injuries in Intensive Care Patients: A Retrospective Cohort Study.

To estimate the direct effects of norepinephrine administration on pressure injury (PI) incidence in intensive care patients. This is a secondary and exploratory analysis of a retrospective cohort study of intensive care patients discharged in 2017 to 2018. Observational cases only included patients who received primary PI preventive care during intensive care (N = 479). As a first-choice vasopressor drug, norepinephrine administration was approximated with days of norepinephrine. Linear path models were examined from norepinephrine administration to PI development. The identification of confounding variables and instrumental variables was grounded on directed acyclic graph theory. Direct effects were estimated with instrumental variables to overcome bias from unobserved variables. As models were re-specified with data analysis, the robustness of path identification was improved by requiring graph invariance with sample split. Norepinephrine caused PI development from one stage to another after 4.0 to 6.3 days of administration in this cohort as a total effect (90% CI). The direct effect was estimated to advance the stage of PI at a rate of 0.140 per day of norepinephrine administered (standard error, 0.029; P < .001). The direct effect accounted for about 70% of the total effect on PI development. Estimations with instrumental variables and structural equation modeling showed that norepinephrine administration directly and substantially affected hospital-acquired PI incidence in intensive care patients in this cohort.

RSK4 confers paclitaxel resistance to ovarian cancer cells, which is resensitized by its inhibitor BI-D1870

Many ovarian cancers initially respond well to chemotherapy, but often become drug-resistant after several years. Therefore, analysis of drug resistance mechanisms and overcoming resistance are urgently needed. Paclitaxel is one of the first-choice and widely-used drugs for ovarian cancer, but like most drugs, drug resistance is observed in subsequent use. RSK4 is known as a tumor-suppressor, however, it has increasingly been reported to lead to drug resistance. Here, we found that RSK4 expression was elevated in paclitaxel-resistant ovarian cancer cells using DNA microarray, quantitative real-time PCR, and western blotting analysis. We examined the contribution of RSK4 to paclitaxel resistance and found that paclitaxel sensitivity was restored by RSK inhibitor co-treatment. We analyzed the mechanism by which resistance is developed when RSK4 level is elevated, and accelerated phosphorylation of the downstream translation factor eIF4B was discovered. In the Kaplan-Meier plot, the overall survival time was longer with RSK4 high, supporting its role as a tumor suppressor, as in previous findings, but the tendency was reversed when focusing on paclitaxel treatment. In addition, RSK4 levels were higher in non-responders than in responders in the ROC plotter. Finally, external expression of RSK4 in ovarian cancer cells increased the cell viability under paclitaxel treatment. These findings suggest that RSK4 may contribute to paclitaxel resistance, and that co-treatment with RSK4 inhibitors is effective treatment of paclitaxel-resistant ovarian cancer in which RSK4 is elevated.

Treatment of Oral Lichen Planus: A Systematic Review

Objective: Oral Lichen Planus (OLP) treatment or clinical management is challenging. This systematic review aims to discuss the main therapy used in the management of OLP and the efficacy of every type of treatment to improve the quality of patient life. Methodology: We discussed the publications on the clinical management of oral lichen planus on the PubMed database. Only randomized controlled trials (RCT) conducted in humans were considered. We included randomized controlled trials (RCT) published from 2005/1/1 to 2021/5/28 with symptomatic, clinically, or histologically diagnosed OLP. We compared different active treatments or between active treatment and placebo. Results: Twenty randomized controlled trials involving 931 patient samples were included in the analysis. For the short time treatment (on average 2-8 weeks) of OLP, TCI, including Tacrolimus, pimecrolimus, and Ciclosporin, were similar to TCS, including Clobetasol, triamcinolone in efficacy. Tacrolimus–Triamcinolone resulted in similar outcomes. In addition, Tacrolimus and Ciclosporin showed a statistically higher incidence of local adverse events than triamcinolone and Clobetasol. A few systemic adverse events occurred in the tacrolimus and ciclosporin groups, but they were not serious. Conclusion: Triamcinolone acetonide 0.1% should be the first drug of choice when selecting TCS, and Tacrolimus 0.1% should be the drug of choice when selecting TCI. J Bangladesh Coll Phys Surg 2023; 41: 219-233

Clinical and biochemical assessment of the effect of topical use of coenzyme Q10 versus topical corticosteroid in management of symptomatic oral lichen planus: randomized controlled clinical trial

BackgroundOral lichen planus (OLP) is a chronic mucocutaneous immunologically mediated condition that has a great adverse effect on oral functions. Corticosteroids are still the first drugs of choice used in the treatment of OLP; however, they have extensive medical side effects. The present study was carried out to assess the clinical therapeutic effect of the topical use of coenzyme Q10 (coQ10 or ubiquinol) versus topical corticosteroids in the management of symptomatic OLP and to determine whether the effect, if any, was due to the powerful antioxidant activity of coQ10.Subjects and methodsWe performed a randomized, double blinded controlled trial at the Faculty of Dentistry, Cairo University, Egypt. The study was conducted on 34 patients suffering from symptomatic OLP. Patients were randomly divided into two groups: intervention group (I),who received topical CoQ10 in the form of mucoadhesive tablets (40% CoQ10) 3 times daily for one month and control group (II),who received topical corticosteroid (kenacort in Orabase: triamcinolone acetonide 0.1% 5-g adhesive paste – dermapharm), 4 times daily for one month. Patients were evaluated at one-week intervals using the clinical parameters (score) of pain (VAS) and lesion size. Additionally, salivary levels of malondialdehyde (MDA) were detected in both groups before and after treatment using ELISA. All recorded data were analysed using independent t test, ANOVA followed by Bonferroni post hoc test for lesion size and salivary level of MDA data and Mann–Whitney U test and Friedman test for VAS data.ResultsBoth groups showed a significant reduction in pain and the size of the lesions (p ≤ 0.05) with no statistically significant difference between them (p > 0.05), and this clinical improvement was associated with a reduction in the salivary levels of MDA in both groups.ConclusionsThe topical use of CoQ10 mucoadhesive tablets was as effective as the topical use of triamcinolone acetonide, and its clinical effect was associated with a reduction in the salivary level of MDA.Trial registrationThe study protocol was registered at www.clinicaltrial.gov (NCT04091698) and registration date: 17/9/2019.

A Metformin-Ferulic Acid Salt with Improved Biopharmaceutical Parameters

Though ferulic acid presents great hypoglycemic potential, it possesses limited aqueous solubility, and low oral bioavailability. When associated with metformin, the first-choice drug in Type 2 diabetes treatment, FA demonstrates synergistic hypoglycemic effects, however, it also causes certain undesirable dose-related effects. This study aimed to develop a new ferulic acid - metformin multicomponent system, and incorporate it into a solid dosage form with improved biopharmaceutical parameters. A novel metformin: ferulate (1:1) salt (MFS) was produced, which was properly characterized using differing analytical techniques, including single crystal analysis. Also during the course of the study, a new polymorph of the metformin free base was observed. The MFS was obtained using solvent evaporation methods, which achieved high yields in reproducible process, as well as a 740-fold increase in ferulic acid aqueous solubility. The MFS tablets developed met quality control requirements for this dosage form, as well as revealing excellent performance in vitro dissolution tests, presenting dissolution efficiency values of 95.4 ± 0.5%. Additionally, physicochemical instability was not observed in a study at 40 °C for 3 months for both MFS powder and its tablet form. The MFS product developed is a promising candidate for further Type 2 diabetes clinical study.