Drug Of First Choice Research Articles

Frequency of Hematological Response in Patients with Chronic Myeloid Leukemia (Chronic Phase) with Imatinib After Three Months Presenting to CMH Rawalpindi

Frequency of Hematological Response in Patients with Chronic Myeloid Leukemia (Chronic Phase) with Imatinib After Three Months Presenting to CMH Rawalpindi

The ameliorating effect of Rutin on hepatotoxicity and inflammation induced by the daily administration of vortioxetine in rats

BackgroundVortioxetine (VORTX) is a potent and selective type of selective serotonin reuptake inhibitor (SSRI) that is mainly prescribed for treating major depression along with mood disorders as the first drug of choice. Limited previous findings have indicated evidence of liver injury and hepatotoxicity associated with daily VORTX treatment. Rutin (RUT), which is known for its antioxidant properties, has demonstrated several beneficial health actions, including hepatoprotection. Therefore the current study aimed to evaluate and assess the ameliorative effect of RUT against the hepatotoxic actions of daily low and high-dose VORTX administration.MethodsThe experimental design included six groups of rats, each divided equally. Control, rats exposed to RUT (25 mg/kg), rats exposed to VORTX (28 mg/kg), rats exposed to VORTX (28 mg/kg) + RUT (25 mg/kg), rats exposed to VORTX (80 mg/kg), and rats exposed to VORTX (80 mg/kg) + RUT (25 mg/kg). After 30 days from the daily exposure period, assessments were conducted for serum liver enzyme activities, hepatotoxicity biomarkers, liver antioxidant endogenous enzymes, DNA fragmentation, and histopathological studies of liver tissue.ResultsInterestingly, the risk of liver damage and hepatotoxicity related to VORTX was attenuated by the daily co-administration of RUT. Significant improvements were observed among all detected liver functions, oxidative stress, and inflammatory biomarkers including aspartate aminotransferase (AST), alanine transaminase (ALT), lactate dehydrogenase (LDH), albumin, malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), glutathione S-transferase (GST), total protein, acid phosphatase, N-Acetyl-/β-glucosaminidase (β-NAG), β-Galactosidase (β-Gal), alpha-fetoprotein (AFP), caspase 3, and cytochrom-C along with histopathological studies, compared to the control and sole RUT group.ConclusionThus, RUT can be considered a potential and effective complementary therapy in preventing hepatotoxicity and liver injury induced by the daily or prolonged administration of VORTX.

Evaluation of multidrug resistance in tumors using 99mTc-doxorubicin

Doxorubicin (DOX) is a potent chemotherapeutic agent used as the first-choice drug in treating different types of cancer, such as leukemia, lymphoma, and breast cancer, among others. However, the development of multidrug resistance represents a significant obstacle to the successful treatment of tumors. In this study, we assessed whether labeled DOX could be uptaken by susceptible and multidrug-resistant cell lines and by tumors in vivo in animals. The efficiency of DOX labeling was maintained at around 90% in this work. To evaluate the effect of 99mTc-DOX on cells expressing active P-glycoprotein (Pgp), we utilized cultured human chronic myeloid leukemia K562 cells and the resistant counterpart Lucena 1 cells. Lucena 1 cell line showed overexpression of Pgp that was not observed in K562. Our results suggested that the resistance to labeled or unlabeled DOX can be reversed by Pgp inhibition and can be easily detected. In conclusion, administering 99mTc-DOX into mice enables the differentiation between multidrug-resistant tumors in a non-invasive way and the evaluation of tumor resistance and possible chemosensitizers.

Silibinin's Effects against Methotrexate-Induced Hepatotoxicity in Adjuvant-Induced Arthritis Rat Model.

Methotrexate (MTX) is the first drug of choice to treat several diseases, including rheumatoid arthritis. However, its administration is accompanied by severe side effects, most commonly hepatotoxicity. Hence, alternative therapies with a lower toxicity and fewer side effects are needed. This study aimed to investigate the antioxidant and hepatoprotective effects of silibinin (SIL, natural agent) against MTX-induced hepatotoxicity in an adjuvant-induced arthritis (AIA) rat model. Arthritic rats were treated with SIL (100 mg/kg) and/or methotrexate (2 mg/kg). Non-arthritic rats, arthritic untreated rats, and arthritic rats who received the vehicle were followed in parallel. SIL alleviated the systemic consequences of arthritis by restoring lost weight, decreasing the erythrocyte sedimentation rate, and ameliorating joint damage, which was evident both micro- and macroscopically. Additionally, SIL prevented the histopathological alterations in the liver and significantly reduced the liver damage caused by MTX and AIA, as shown by a decrease in the markers of liver damage (ALT and AST). Furthermore, SIL relieved the oxidative stress induced by AIA and MTX in liver tissue by decreasing the lipid peroxidation (MDA) levels and enhancing the antioxidant defense system (GSH levels; catalase and superoxide dismutase (SOD) activities). In conclusion, our results suggest that SIL is a potent antioxidant and hepatoprotective agent in arthritic rats. It markedly attenuated the progression and severity of the arthritic disease and eased the oxidative stress in liver tissue by improving the pro-oxidant/antioxidant balance.

Studying the Blood Trough Level of Tacrolimus on Patients after Kidney Transplant at the Uronephreulogical Department, Bach Mai Hospital, Vietnam

Tacrolimus, a calcineurin inhibitor, is a first-choice drug for the anti-rejection treatment regimen after kidney transplantation. The daily adjusted Tacrolimus dose by therapeutic drug monitoring is essential for patients to achieve optimal effects and minimize complications. We conducted a retrospective analysis of 70 kidney transplant patients at Bach Mai Hospital from January 2019 to the end of June 2020 to monitor changes in the blood trough level of Tacrolimus over time and analyze some risk factors affecting the blood trough level of Tacrolimus after a kidney transplant. Total whole-blood samples were collected at 6 time points: pre-transplant, on transplant day, and the 1st, 2nd, 4th, and 8th day after surgery. During the study, we recorded 4 cases with accelerated acute rejection with the blood trough level of Tacrolimus on the first day after transplantation of 5.325 ± 1.531 ng/mL and lower than the medium level in the remaining group of patients 10.371 ± 4.550 ng/mL at the same time (p = 0.031). There was no significant difference between the two groups of patients in age, gender, BMI, chronic disease status (hypertension, hepatitis C, type 2 diabetes), pre-transplant blood urea, and serum creatinine concentrations. These characteristics were included in the linear regression models which affected the blood trough level of Tacrolimus. This showed that none of the above risk factors had a significant effect on the blood trough level of Tacrolimus on the first day after transplantation (p > 0.05).
  
  

Migraine treatment – updated recommendations 2024 –development of the Expert Group of the Headache Section ofthe Polish Neurological Society and the Polish Society for theStudy of Pain

Migraine is one of the most frequent disabling neurological conditions with a major impact on the patients qualityof life. Migraine treatment recommendations are provided based on a review of the literature from randomizedclinical trials and the consensus of a national expert panel. All available medical reference systems were screened for the range of past and present clinical studies on migraine with and without aura and on migraine-like syndromes.The results of these studies were presented in accordance with the recommendations of the Migraine Section ofthe Polish Neurological Society and the Polish Society for the Study of Pain. For the acute treatment of migraineattacks, oral non-steroidal antiinflammatory drug (NSAID), triptans and new class of drugs gepants and ditans arerecommended. The administration should follow the concept of stratified treatment. Before intake of NSAID andtriptans, oral metoclopramide is recommended. In very severe attacks, subcutaneous sumatriptan are drugs of firstchoice. Status migrainosus can be treated by cortoicosteroids, although this is not universally held to be helpful. Forthe prophylaxis of migraine, old and new drugs – betablockers flunarizine, valproic acid, and topiramate as well asmonoclonal anti CGRP antibodies, gepants and botulin toxin are drugs of first choice.

Treatment adherence and the contemporary approach to treating type 2 diabetes mellitus.

The rising burden of type 2 diabetes mellitus (T2D) poses a significant healthcare challenge on a global scale. The economic impact is also substantial and continually increasing. In Serbia, even though the prevalence is officially around 12 percent, nearly 40 percent of the adult population is estimated to be living with undiagnosed diabetes and more than half the population is obese or overweight. This review comprehensively addresses the present approach to treating T2D, emphasizing the critical role of treatment adherence. We review the various components of T2D treatment, underlining the significance of lifestyle modifications. The pros and cons of medications used in treatment are discussed and factors influencing adherence are analysed. A healthy lifestyle remains the foundation of the treatment, and if not sufficient, early pharmacotherapy is initiated. Medications have been developed to lower blood sugar levels with cardiorenal protection, however, due to their still high cost, metformin remains the drug of first choice for most patients. Adherence to the treatment regimen is often poor. Factors associated with this are diverse and often multiple in a particular patient. Poor adherence is associated with poor glycaemic control, increased risk of disease complications, higher cardiovascular risk, increased mortality, hospitalizations, and healthcare costs. In addition to reducing the complexity of drug therapy and better informing the patient, improved education and motivation could lead to greater adherence. Enhanced communication between the patient and the physician and reduced treatment costs could also have a positive impact. The review concludes that addressing factors affecting adherence can significantly improve T2D outcomes and reduce costs. Further research is needed to identify region-specific risk factors for poor adherence.

Cardiotoxic Effects Produced by Omeprazole and Methylene Blue in an Animal Model of Cardiac Ischemia and Reperfusion and Potential Implications for the Pharmacological Strategy for Vasoplegic Syndrome.

Defined as systemic hypotension caused by intense vasodilation due to the loss of systemic vascular resistance, vasoplegic syndrome (VS) is associated with elevated morbidity and mortality in humans. Although vasopressors such as norepinephrine and vasopressin are the first-choice drugs for VS treatment, several other drugs such as methylene blue (MB) can be used as adjuvant therapy including rescue therapy. To develop new pharmacological strategies to reduce the risk of VS, we investigated the effects of treatments with MB (2 mg/kg/IV), omeprazole (OME, 10 mg/kg/IV), and their combination in an animal model of cardiac ischemia-reperfusion (CIR). The ventricular arrhythmia (VA), atrioventricular block (AVB), and lethality (LET) incidence rates caused by CIR (evaluated via ECG) and serum levels of the cardiac lesion biomarkers creatine kinase-MB (CK-MB) and troponin I (TnI) in adult rats pretreated with saline solution 0.9% and submitted to CIR (SS + CIR group) were compared to those pretreated with MB (MB + CIR group), OME (OME + CIR group), or the MB + OME combination (MB + OME + CIR group). The AVB and LET incidence rates in the MB + CIR (100%), OME + CIR (100%), and MB + OME + CIR (100%) groups were significantly higher compared to the SS + CIR group (60%). The serum level of CK-MB in these groups were also significantly higher compared to the SS + CIR group, demonstrating that the treatments before CIR with MB, OME, and MB + OME produced similar effects in relation to cardiac function and the occurrence of lesions. These results demonstrate that the treatment of animals subjected to the CIR protocol with OME produced the same effects promoted by the treatment with MB, which may suggest the possibility of using OME alone or in combination with MB in medical clinics in treatment of VS.

Exploring novel pyrazole-nitroimidazole hybrids: Synthesis and antiprotozoal activity against the human pathogen trichomonas vaginalis

Trichomoniasis, a prevalent sexually transmitted infection (STI) caused by the protozoan Trichomonas vaginalis, has gained increased significance globally. Its relevance has grown in recent years due to its association with a heightened risk of acquiring and transmitting the human immunodeficiency virus (HIV) and other STIs. In addition, many publications have revealed a potential link between trichomoniasis and certain cancers. Metronidazole (MTZ), a nitroimidazole compound developed over 50 years ago, remains the first-choice drug for treatment. However, reports of genotoxicity and side effects underscore the necessity for new compounds to address this pressing global health concern. In this study, we synthesized ten pyrazole-nitroimidazoles 1(a-j) and 4-nitro-1-(hydroxyethyl)-1H-imidazole 2, an analog of metronidazole (MTZ), and assessed their trichomonacidal and cytotoxic effects. All compounds 1(a-j) and 2 exhibited IC50 values ≤ 20 μM and ≤ 41 μM, after 24 h and 48 h, respectively. Compounds 1d (IC50 5.3 μM), 1e (IC50 4.8 μM), and 1i (IC50 5.2 μM) exhibited potencies equivalent to MTZ (IC50 4.9 μM), the reference drug, after 24 h. Notably, compound 1i showed high anti-trichomonas activity after 24 h (IC50 5.2 μM) and 48 h (IC50 2.1 μM). Additionally, all compounds demonstrated either non-cytotoxic to HeLa cells (CC50 > 100 μM) or low cytotoxicity (CC50 between 69 and 100 μM). These findings suggest that pyrazole-nitroimidazole derivatives represent a promising heterocyclic system, serving as a potential lead for further optimization in trichomoniasis chemotherapy.

Dermorphin [D-Arg2, Lys4] (1-4) Amide Alleviates Frostbite-Induced Pain by Regulating TRP Channel-Mediated Microglial Activation and Neuroinflammation.

Cold injury or frostbite is a common medical condition that causes serious clinical complications including sensory abnormalities and chronic pain ultimately affecting overall well-being. Opioids are the first-choice drug for the treatment of frostbite-induced chronic pain; however, their notable side effects, including sedation, motor incoordination, respiratory depression, and drug addiction, present substantial obstacle to their clinical utility. To address this challenge, we have exploited peripheral mu-opioid receptors as potential target for the treatment of frostbite-induced chronic pain. In this study, we investigated the effect of dermorphin [D-Arg2, Lys4] (1-4) amide (DALDA), a peripheral mu-opioid receptor agonist, on frostbite injury and hypersensitivity induced by deep freeze magnet exposure in rats. Animals with frostbite injury displayed significant hypersensitivity to mechanical, thermal, and cold stimuli which was significant ameliorated on treatment with different doses of DALDA (1, 3, and 10 mg/kg) and ibuprofen (100 mg/kg). Further, molecular biology investigations unveiled heightened oxido-nitrosative stress, coupled with a notable upregulation in the expression of TRP channels (TRPA1, TRPV1, and TRPM8), glial cell activation, and neuroinflammation (TNF-α, IL-1β) in the sciatic nerve, dorsal root ganglion (DRG), and spinal cord of frostbite-injured rats. Treatment with DALDA leads to substantial reduction in TRP channels, microglial activation, and suppression of the inflammatory cascade in the ipsilateral L4-L5 DRG and spinal cord of rats. Overall, findings from the present study suggest that activation of peripheral mu-opioid receptors mitigates chronic pain in rats by modulating the expression of TRP channels and suppressing glial cell activation and neuroinflammation.

P877 A comparison of vedolizumab and ustekinumab treatment in patients with Ulcerative Colitis after failure of treatment with tumor necrosis factor inhibitor

Abstract Background Data comparing vedolizumab (VDZ) and ustekinumab (UST) in patients with ulcerative colitis (UC) previously treated with tumor necrosis factor inhibitor (TNFi) and followed with regular serum-drug measurements are scarce. In the national pharmaceutical tender system of Norway, VDZ was listed as the first drug of choice after failed TNFi treatment from 2016 to 2019 and UST from 2020 to 2022. We aimed to compare drug persistence, effectiveness, drug dosing and disease activity in patients treated with VDZ or UST after failed TNFi therapy. Methods We included patients who had failed at least one TNFi and started either VDZ treatment (years 2016-2019) or UST (years 2020-2022). Patients were followed for one year after initiating the treatment or until discontinuation. Prospectively recorded data were obtained from the electronic patient journal (EPJ) and the local IBD-registry. Clinical remission was defined as 6-point Mayo Score ≤1, and biochemical remission was defined as CRP<5 mg/L and FC<250 µg/g. Patients were followed with regular serum-drug measurements and dose adjustments were made at the discretion of the treating physician based on serum-drug measurements and clinical activity at follow-up visits. Wilcoxon signed rank and Mann Whitney U test were used to assess differences in paired and unpaired data, respectively. Results A total of 116 patients were included, 59 treated with VDZ and 57 with UST. At 52 weeks, there was no difference in estimated drug persistence with 85% [73-92] for VDZ and 92% [80-96] for UST. Clinical remission increased significantly in both groups (Table 1), and no difference was found between UST and VDZ for clinical remission at week 0 and 52 (OR=2.1 [0.9-4.5] and OR=0.9 [0.3-2.3]). Contrary to the VDZ group, there was a significant decrease in CRP from week 0 to 52 in the UST group, while FC decreased significantly in both groups (Table 1). The proportion of patients in biochemical remission increased in the UST group while there was no significant change in the VDZ group. Significantly more patients treated with UST received an intensified treatment regime at 52 weeks (interval less than eight weeks) compared to VDZ treated patients (87% (95% CI [74-94]) vs 59% (95% CI [45-72])). Conclusion This study demonstrates that one-year drug persistence and clinical remission were high and comparable in both UST and VDZ treated UC patients with previous TNFi failure. Treatment with UST, but not VDZ, was associated with a significant increase in the proportion of patients in biochemical remission from induction to 52 weeks. However, a significantly larger proportion of patients treated with UST received intensified dosing at 52 weeks compared with VDZ treated patients.

A rapid-floating natural polysaccharide gel–raft with double-effect for the treatment of gastroesophageal reflux disease

Gastroesophageal reflux disease (GERD) is a prevalent gastrointestinal condition characterized by regurgitating stomach contents into the esophagus, causing mucosal damage or erosion. Clinical physical protection treatment mainly relies on the use of floating rafts. Bletilla striata (BS) is widely regarded as the first-choice drug for treating digestive tract injuries in Chinese Medicine. The rapid-floating gel-raft (B-R) was prepared via a one-step swelling method using natural BS polysaccharide and glyceryl monooleate. Panax notoginseng saponins (PNS) were loaded to further prepare P/B-R according to clinical experience. Possessing hydrophobic dense, stratified porous structure and stable rheological properties, an outperforming floating performance of P/B-R was proven compared with Gaviscon® (alginate-antacid formulation) in vitro. In vivo imaging results showed that P/B-R can retain and adhere to the gastric mucosa of rats for up to 90 min, protecting and repairing the mucosa. Besides physical protection in situ, the systemic effects of antioxidant and anti-inflammatory actions for treating GERD were achieved through the intestinal release of PNS. Acid-labile PNS was protected by P/B-R against gastric acid, attaining the desired release and permeability. A significantly effective mucosa injury protective effect of P/B-R was found in ethanol-induced gastric damage model on rats. Moreover, P/B-R exhibits excellent biosafety at the cellular level.

Pharmacological therapy in the management of temporomandibular disorders and orofacial pain: a systematic review and meta-analysis

BackgroundTemporomandibular disorders (TMD) are manifested by soreness in the jaw joint area and jaw muscles, clicks or creaks when opening or closing the mouth. All these symptoms can be disabling and occur during chewing and when the patient yawns or speaks. Several classes of drugs are used to treat symptoms. This review aims to assess which drug suits the different signs.MethodsPubmed, Web of Science and Lilacs were systematically searched until 01/02/2023. Clinical trials were selected that dealt with drugs used in temporomandibular dysfunctionResultsOut of 830 papers, eight studies were included. The Meta-Analysis with Continuous Outcomes with Pre-Calculated Effect Sizes resulted in the rejection that there is intergroup variability (p.0.74).ConclusionsTreatment of orofacial pain is still a significant challenge for dentistry. We can conclude that there is no drug of first choice in the treatment of temporomandibular pain. However, the clinician must distinguish the type of pain and the aetioloic cause of the pain so that the patient can be treated and managed pharmacologically.

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.