Drug Of Choice Research Articles

Role of enzyme replacement therapy for exocrine and nutritional insufficiency in patients with malignancies: A review

Exocrine pancreatic insufficiency (EPI) is a condition in which the amount of secreted pancreatic enzymes is insufficient to maintain normal digestion. EPI is a frequent complication of pancreatic or other malignancies. The presence of EPI in a cancer patient may be suggested by symptoms of maldigestion, malabsorption, and alteration of nutritional markers; however, it is important to note that the EPI symptoms may be subtle. In the early stages, EPI may be latent and manifested by malnutrition. However, even in the later stages, the symptoms of EPI may be similar to those of cancer or be masked by the condition after chemoradiation therapy. Antitumor therapy itself may also cause EPI. Enzyme replacement therapy (ERT) is the standard of care for EPI, but it is rarely prescribed to cancer patients. However, supportive therapy plays an essential role in treating cancer patients because the quality of life and life expectancy of patients largely depend on the adequacy of the complex treatment. The review discusses the possible causes of EPI and its diagnosis and treatment in cancer patients. Special attention is paid to ERT regimens, including those for improving digestion and the drug's dosage form. It is shown that pancreatin in minimicrospheres is the drug of choice for ERT, since the minimum particle size facilitates the most physiological digestion process.

On the choice of antiarrhythmic drug in patients with ventricular arrhythmia of mixed character

Background. The choice of an antiarrhythmic drug, proof of its effectiveness and safety in a short period of time in patients with non-coronary ventricular arrhythmia are the most pressing problems of practical arrhythmology. Objective. To resolve the issue of choosing an antiarrhythmic drug in patients with a mixed nature of ventricular arrhythmia, several ectopic foci, and to optimize further tactics for their management. Design and methods. Of 167 patients with ventricular arrhythmia distribution during periods of wakefulness who performed a stress test, 32 individuals with non-coronary arrhythmias of a mixed nature (by the participation of the autonomic nervous system) were selected. All patients underwent an acute pharmacological stress test with a beta-blocker. Antiarrhythmic therapy was selected under the control of multi-day ECG telemonitoring. Results. In the pretest of exercise tests, single ventricular parasystole was recorded in all 32 patients. In 3 patients, the arrhythmia persisted throughout the entire load, in 4 patients it progressed, in 25 patients the parasystole of the initial morphology disappeared, and at the peak of the load/early recovery period, arrhythmia of a different morphology appeared. Indications for drug treatment were determined for all patients with the choice of the drug after acute pharmacological tests. Then, therapy with two antiarrhythmic drugs was initiated using multi-day ECG telemonitoring, the purpose of which was to control the efficacy, safety, choice of doses and time of drug administration. On days 5–6, combination therapy was effective in 25 patients (78 %). Conclusion. With the help of stress tests, it is possible to accelerate not only the search for the cause of ventricular arrhythmia, but also the choice of a personalized method of treatment. Supplementing the examination with pharmacological tests allows predicting the result of combined antiarrhythmic therapy with a beta-blocker and a class IС drug with an anticholinergic effect.

Lithium - Fifteen Years Later.

The 75th anniversary of introducing lithium into modern psychiatry is recognized, attested by the 1949 paper of John Cade. About this event, my editorial in the special 2010 issue of Neuropsychobiology was titled "Lithium: Sixty Years Thereafter". Since then, fifteen more years have brought further information about lithium. This paper makes a narrative review of the most important articles published in this period. The selected key literature of 2010-2024 addressed lithium prophylactic efficacy in bipolar disorder (BD), including pediatric, recurrent depression, and lithium augmentation of antidepressants in treatment-resistant depression (TRD). Novel data have been obtained for lithium adverse effects (kidney, thyroid) and beneficial outcomes of long-term lithium administration (anti-suicidal, neuroprotective, antiviral, and others). The results on the mechanisms of lithium action covered genetic investigations of the ConLiGen, and in vitro studies with induced pluripotent stem cells and lymphoblastoid cell lines. The underutilization of lithium nowadays was emphasized, and the ways to overcome it were considered. Lithium remains the choice drug for recurrence prevention in BD, also in adolescents, and a significant option for augmentation of antidepressants in TRD. The adverse side effects should be carefully followed and managed according to current guidelines. There are also beneficial lithium impacts, of which anti-suicidal and anti-dementia seem the most important. Most of the results of neurobiological studies on lithium mechanisms may be related to lithium response and some (e.g. immunomodulatory) to the pathogenesis of BD. Better education about lithium could make more patients the beneficiary of this drug.

Spatio-temporal localization of P21-activated kinase in endometrial cancer.

Endometrial cancer is the sixth most common gynecologic cancer, and has been reported as a malignancy arising due to the idiopathic effects of certain anticancer agents. Tamoxifen is the drug of choice in ER-positive breast cancer, and several studies have shown better disease-free survival in these patients. However, the long-term usage of tamoxifen has been associated with resistance and risk for endometrial malignancy. A direct mechanistic basis for tamoxifen-induced endometrial tumorigenesis is still unclear. Hyperactivation of PAK1 in endometrial cancer correlates with poor overall survival. The present study demonstrates that tamoxifen treatment induces nuclear localization of PAK1 in endometrial carcinoma cells. This nuclear transit is mediated through JAK2 phosphorylation of PAK1 and binding of β-PIX. In addition, a computational approach involving molecular modeling and simulation of phosphorylated and unphosphorylated forms of PAK1 was used to elucidate the dynamics of nuclear localization. Thus, PAK1 phosphorylation by JAK2 is a prerequisite for its nuclear localization and its tumorigenic effects on endometrial cancer cells.

Chronic pain among primary fentanyl users: The concept of self-medication.

Chronic pain is among the leading causes of disability worldwide, of which only a small percentage of patients receive adequate treatment for. Non-prescribed opioid analgesics are commonly sought out in effort to alleviate unrelieved pain. This study assesses the prevalence and correlates of chronic pain among primary fentanyl users. A cross-sectional and structured survey was conducted with 200 adults who reported fentanyl as their drug of choice from a Vancouver acute care hospital. Presence and levels of chronic pain were determined through self-report. The majority of participants (n = 130, 72.6%) reported having chronic pain in the past 6 months, with the mean level of pain on a typical day to be 7.6 out of a scale of 10 (SD = 1.9). Majority (n = 85, 65.4%) reported using street opioids to self-medicate, while only 9 (6.9%) reported that their chronic pain was unrelated. Regression analysis indicated that increasing age and co-use of cannabis and opioids were independent associated factors of chronic pain. Higher levels of reported pain on a typical day were further associated with age and self-medication. The findings of this study demonstrate a significant association between self-medication and chronic pain among primary fentanyl users in British Columbia. For these individuals, inadequate pain relief may drive continued opioid use, which in turn may increase risks of treatment discontinuation and overdose. Appropriate pain management strategies are crucial to avoid opioid misuse and decrease the large societal burden caused by chronic pain. Our work points to the high prevalence of self-reported chronic pain among individuals who primarily use fentanyl. Among those with self-reported fentanyl use and chronic pain, self-medication with street opioids was found to be common and associated with higher reported pain levels on a typical day. This highlights the need for pain management strategies to be integrated into opioid dependence treatment and more research in the overlap of pain and fentanyl use.

Drug resistance and possible therapeutic options against influenza A virus infection over past years.

Influenza A virus infection, commonly known as the flu, has persisted in the community for centuries. Although we have yearly vaccinations to prevent seasonal flu, there remains a dire need for antiviral drugs to treat active infections. The constantly evolving genome of the influenza A virus limits the number of effective antiviral therapeutic options. Over time, antiviral drugs become inefficient due to the development of resistance, as seen with adamantanes, which are now largely ineffective against most circulating strains of the virus. Neuraminidase inhibitors have long been the drug of choice, but due to selection pressure, strains are becoming resistant to this class of drugs. Baloxavir marboxil, a drug with a novel mode of action, can be used against strains resistant to other classes of drugs but is still not available in many countries. Deep research into nanoparticles has shown they are effective as antiviral drugs, opening a new avenue of research to use them as antiviral agents with novel modes of action. As this deadly virus, which has killed millions of people in the past, continues to develop resistance, there is an urgent need for new therapeutic agents with novel modes of action to halt active infections in patients. This review article covers the available therapeutic antiviral drug options with different modes of action, their effectiveness, and resistance to various strains of influenza A virus.

Western Anthelmintics in Early Twentieth-Century China Colonial Practices and Knowledge on "Tropical Diseases" of the In/between.

Protestant (medical) missionaries were the main proponents of Western medicine in China after the Opium Wars. Several studies have highlighted how they used spectacular surgery as a means of gaining public trust. As well as surgery, they also administered anthelmintic drugs such as santonin as a tool of persuasion and conversion. Many anthelmintic drugs of the European materia medica had a colonial history. My paper analyses how coloniality materialised in medical practice and anthelmintics in China. For the late nineteenth century, I will examine the colonial practices in which the drug santonin was involved. At the time, santonin was the drug of choice for treating roundworm. In the early twentieth century, medical missionaries became involved in parasitological research on parasitic worms such as hookworm and Fasciolopsis buski. For this period, I will explore how new knowledge about anthelmintics emerged in the scattered knowledge space of China, and how it related to colonialism and imperialism.

Current and future medical treatment for endometriosis

Endometriosis is a chronic, progressive inflammatory disease that occurs in approximately 10% of women of reproductive age, resulting in a decreased quality of life due to dysmenorrhea, chronic pain, and other problems. The primary treatment is pain control and fertility preservation, and while preserving ovarian function through drug therapy and surgery, assisted reproductive technology (ART), including in vitro fertilization (IVF), is also utilized. Hormonal therapies such as low-dose estrogen/progestin (LEP), progestins, and GnRH analogs are often the drug of choice. We presented that IAP (inhibitor of apoptotic protein) inhibitors can potentially be novel agents for treating endometriosis. Our studies using cultured cells derived from human endometriotic lesions and mouse models have revealed that inflammatory cytokines and antiapoptotic factors (IAPs) produced by peritoneal macrophages or endometriosis cells are crucial and that NF-κB (nuclear factor-kappa B) plays a central role in the pathogenesis of endometriosis. The high expression of IAPs in human endometriotic tissues, its facilitative role in ectopic survival, and the effect of IAPs on drug-resistant apoptosis of human endometriotic cells indicate its potential as a novel drug for IAP inhibitors. We found that the medicinal herb parthenolide and selective estrogen receptor modulators (SERM) can reduce lesions through NF-κB inhibition. Recently, new findings were obtained by non-invasive observation of early lesions using bioluminescence technology and by applying knockout mouse models. We will show the possibility of new therapeutic agents for endometriosis.

Nodularin-R Synergistically Enhances Abiraterone Against Castrate- Resistant Prostate Cancer via PPP1CA Inhibition.

Clinically, most prostate cancer (PCa) patients inevitably progress to castration-resistant prostate cancer (CRPC) with poor prognosis after androgen deprivation therapy (ADT), including abiraterone, the drug of choice for ADT. Therefore, it is necessary to explore the resistance mechanism of abiraterone in depth. Genome-wide CRISPR/Cas9 knockout technology was used to screen CRPC cell line 22Rv1 for abiraterone-resistant genes. Combined with bioinformatics, a key gene with high expression and poor prognosis in CRPC patients was screened. Then, the effects of target gene on abiraterone-resistant 22Rv1 cell function were explored by silencing and overexpression. Further, a natural product with potential targeting effect was identified and validated by molecular docking and protein expression. Molecular dynamics simulations revealed potential mechanism for the natural product affecting target protein expression. Finally, the combined anti-CRPC effects of the natural product and abiraterone were validated by cellular and invivo experiments. Five common resistance genes (KCNJ3, COL2A1, PPP1CA, MDH2 and EXOSC5) were identified successfully, among which high PPP1CA expression had the worst prognosis for disease-free survival. Moreover, PPP1CA was highly expressed in abiraterone-resistant 22Rv1 cells. Silencing PPP1CA increased cell sensitivity to abiraterone while promoting apoptosis and inhibiting clone formation. Overexpressing PPP1CA exerted the opposite effects. Molecular docking revealed the binding mode of the natural product nodularin-R to PPP1CA with a dose-dependent manner for inhibition. Mechanistically, nodularin-R attenuates the interaction between PPP1CA and USP11 (deubiquitinating enzyme), potentially promoting PPP1CA degradation. Additionally, combination of 2.72 μM nodularin-R and 54.5 μM abiraterone synergistically inhibited the resistant 22Rv1 cell function. Invivo experiments also revealed that combination therapy significantly inhibited tumour growth and reduced inducible expression of PPP1CA. PPP1CA is a key driver for abiraterone resistance, and nodularin-R enhances the anti-CRPC effects of abiraterone by inhibiting PPP1CA.

Effect of metformin therapy on the development of vitamin B12 deficiency in patients with type 2 diabetes mellitus

Introduction. For the past decades, metformin has been the drug of choice for the treatment of patients with type 2 diabetes mellitus (T2DM). However, its long-term use leads to a number of side effects, such as the development of vitamin B12 deficiency (VB12).Aim. Assess the safety of metformin use in real clinical practice in the treatment of patients with type 2 diabetes based on the analysis of the incidence of VB12 deficiency.Materials and methods. Sixty patients with T2DM aged 27 to 65 years were examined in a city polyclinic. The average anamnestic duration of T2DM was 68 [4; 291] months. All patients were on selected hypoglycemic therapy: 19 patients (31.7%) received metformin monotherapy, and 41 patients (68.3%) received metformin as part of combination therapy. The average duration of metformin therapy was 62 [3; 291] months. All patients underwent analysis of the VB12 content in the blood serum depending on the duration of metformin intake. Results. The average VB12 level in the examined patients was 345 [99; 770] pg/ml. Normal VB12 levels were observed in 51 (85%) patients (386 [221; 770] pg/ml), VB12 deficiency (<200 pg/ml) was detected in 9 (15%) patients (146 [99; 195] pg/ml), the differences between VB12 levels were significant (p < 0.05). At the same time, in 37 (61.7%) patients with normal VB12 levels, its values were assessed as borderline (in the range of 200–450 pg/ml), and amounted to 335 [221; 470] pg/ml. VB12 deficiency developed more often in patients taking metformin for more than 1 year (16.7%), borderline VB12 levels were more often found in patients taking metformin for less than a year (58.3%) and more than 5 years (71%). However, the dependence of VB12 levels on the duration of metformin intake was not significant (p > 0.05).Conclusion. Metformin use results in the development of VB12 deficiency in every sixth patient with T2DM, primarily after one year of treatment.

In-utero exposure to tenofovir-containing pre-exposure prophylaxis and bone mineral content in HIV-unexposed infants in South Africa.

Tenofovir disoproxil fumarate (TDF) is a common drug of choice for pre-exposure prophylaxis (PrEP) or as a combination HIV treatment for pregnant women. In-utero exposure to TDF was found to be associated with lower bone mineral content (BMC) in HIV-exposed uninfected neonates. Data for infants born to women taking TDF-PrEP are lacking. The CAP016 randomized control trial was conducted in South Africa between September 2017 and August 2021 and pregnant women either initiated TDF/FTC PrEP in pregnancy (Immediate PrEP arm-IP) or at cessation of breastfeeding (Deferred PrEP arm-DP). In a secondary data analysis, we evaluated BMC in HIV-unexposed infants in the CAP016 trial in the first 18 months of life in association with maternal TDF-PrEP use during pregnancy. Infants born to women randomized to the IP arm or DP arm in the CAP016 clinical trial had BMC measurements of the whole body with head (WBH) and lumbar spine (LS) by dual energy X-ray absorptiometry (DXA) at 6, 26, 50 and 74 weeks. Of 481 infants born to women enrolled in the CAP016 clinical trial, 335 (69.6%) infants had a minimum of one DXA scan of the WBH and LS between 6 and 74 weeks of age (168 IP and 167 DP). Women in the IP arm received TDF-FTC PreP for a median of 19 weeks between initiation in pregnancy and delivery. Using a mixed linear regression model and adjusted for gestational age, sex and ever-breastfed, the mean difference (95% CI) for BMC of the WBH between IP and DP arms were -0.74 (-8.69 to 7.20), -1.26 (-10.75 to 8.23), -9.17 (-20.02 to 1.69) and 5.02 (-6.74 to 16.78) g at 6, 26, 50 and 74 weeks (p = 0.283). Mean differences in BMC of the LS were 0.07 (-0.10 to 0.23), 0.02 (-0.18 to 0.22), -0.14 (-0.36 to 0.09) and 0.14 (-0.11 to 0.38) g at 6, 26, 50 and 74 weeks, respectively (p = 0.329). In a randomized controlled trial, there were no differences in BMC of the WBH and LS between infants exposed to in-utero TDF-FTC PrEP and unexposed infants in the first 18 months of life.

Application of mPEG-PCL-mPEG Micelles for Anti-Zika Ribavirin Delivery.

Nanoparticles are rapidly becoming the method of choice for a number of nanomedicine applications, especially drug delivery. Many current nanoparticle models for drug delivery include a metal base with a drug conjugated to its surface. However, this raises concerns regarding toxicity since the conjugated drug and metal-based center of the nanoparticle are generally not biocompatible. A novel approach to solve this dilemma is the development of nanosized biocompatible polymer-based micellar nanoparticles (MNPs), created from methoxy poly(ethylene-glycol) poly(ɛ-caprolactone)-methoxy poly(ethylene glycol) (i.e., mPEG-PCL-mPEG) triblock polymers formed around an antiviral drug of choice, ribavirin. The goal is to create a drug carrier triblock nanoparticle system that is labile at a specific intercellular pH resulting in drug release, leading to the suppression of viral pathogens, and without undue toxicity to the cell. Through this approach we created a drug-loaded nanoparticle that dissociates when exposed to pH of 5.49 (endosomal pH), releasing ribavirin intercellularly, resulting in effective suppression of the mosquito-borne virus, Zika, in JEG-3 cells (gestational choriocarcinoma cells), in comparison to untreated and unencapsulated ribavirin controls as shown by plaque reduction assays and confirmation by RT-PCR. The level of suppression observed by ribavirin-loaded MNPs was achieved while requiring approximately 90% less ribavirin than in experiments utilizing unencapsulated ribavirin. The drug delivery system that is described here has shown significant suppression of Zika virus and suggests a role for this drug delivery system as an antiviral platform against additional viral pathogens.

Which antidiabetic drugs do patients of T2DM prefer in India and why? A discrete choice experiment

ABSTRACT Background: Uncontrolled diabetes persists despite guideline-based treatment, partly attributed to inadequate patient involvement. This research addresses shared decision-making by eliciting patient preferences in Type 2 Diabetes Mellitus (T2DM) treatment based on certain key attributes and explores their correlation with socio-demographic-clinical profiles. Methods: A discrete choice experiment (DCE) was conducted among T2DM outpatients in an Indian tertiary care center. A choice card was developed using the contextual choice framework, having six second-line antidiabetic drugs (ADs) from different classes incorporating seven attributes. Face-to-face interviews were conducted with patients, and elicited preferences were analyzed using descriptive statistics, Chi-square analysis, and multinomial logistic regression. Results: Out of the 87 evaluated participant choices, the most preferred drug was Glimepiride (51.7%), followed by Dapagliflozin (22.9%) and Teneligliptin (17.2%). Overall, the most important attributes were the effect on weight (29%), followed by route of administration (24%), and additional benefits offered by the drug (18%). Significant associations were found between participants’ drug preferences and their age (P = 0.002), socioeconomic status (P = 0.04), occupation (P = 0.004), and monthly income (P = 0.03). Age was not a significant predictor of drug choice for any of the drugs. Multinomial logistic regression showed that the overall model was statistically significant (P = 0.025), and it correctly predicted drug choice for 58.6% of the participants. Conclusion: Glimepiride was the most preferred option overall while the effect on weight was the most important attribute for patients in determining their preference. The study highlighted the importance of shared decisions and can guide practitioners in considering patient preferences when prescribing antidiabetic drugs.

Adverse cardiological and neurological reactions associated with air traffic and the possibility of their pharmacological correction

Air transport may provoke or aggravate a medical event in a passenger with concomitant medical problems. We searched the PubMed and Scopus databases for the period up to 08/29/2024 for sources that examined the impact of air travel on human health. There are 2 main categories of stressors associated with air travel and affecting the body, generally divided into:(1) psychological and physical stressors and (2) physiological Possible changes in health associated with air travel can be divided into functional, mostly reversible, and organic: (1) exacerbation/decompensation of existing somatic pathology;(2) development of pathological conditions de novo, for which possible stressors can serve as a trigger, directly or sequentially as a result of the previous development and progression of functional disorders. The literature focuses on safety issues during air travel for patients with existing cardiovascular pathology. Adverse functional cardiological and neurological reactions and their pharmacological correction have been less studied. Fear of flying and phobia of flying are very common among the general population and can lead to significant stress. For situational correction of reactions to everyday stressful events, it is possible to use drugs with anxiolytic action of a non-benzodiazepine This group includes the drug Valocordin®, the action of which is aimed at various manifestations of stress, anxiety states, autonomic dysfunction, increased excitability and irritability, mild sleep disorders. In case of pre-flight anxiety and fear, taking Valocordin® (depending on the situation or in a short course) can be the drug of choice for both the air traveler and his relatives seeing him off/meeting him.

A comparative study of two different doses of dexmedetomedine as an adjuvant to lignocaine in infiltration block for tympanoplasty: a triple-blinded, prospective, randomized controlled trial.

The ideal anesthetic drug choice for local infiltration anesthesia under monitored anesthesia care must provide analgesia and patients' comfort along with a bloodless surgical field for patients. We hypothesized that dexemedetomidine can provide better visibility of the surgical field at a higher dose of 1 µg/kg than 0.5 µg/kg, along with providing sedation and analgesia. After institutional ethics committee clearance and written informed consent, this prospective, randomized, triple blind study was conducted on ninety patients, between 18- 65 years who were scheduled for tympanoplasty. The patients were randomly assigned to either the dexmedetomidine (DEX) 0.5 group or the DEX 1.0 group, and received 10 ml solution containing 2% lignocaine with 0.5 µg/kg dexmedetomidine, or the 1 µg/kg dexmedetomidine. The operative surgeon performed local infiltration using standardized 5-point infiltration technique around the auricle. The primary objective was to compare the intraoperative bleeding at the surgical site. The comparison of normally distributed variables was conducted using the Student's t-test, whereas non-normally distributed variables was compared using the Mann-Whitney U test. The analysis of qualitative data was conducted using the chisquare/Fisher's exact test. A P value less than 0.05 was considered statistically significant. The overall bleeding score was significantly higher in the DEX 0.5 group (3.21 ± 0.727) than the DEX 1.0 group (1.43 ± 0.661) (P value < 0.001). The time to first analgesic requirement and surgeon satisfaction score were also significantly higher in the DEX 1.0 group. Combining dexmedetomidine at a dose of 1 µg/kg with 2% lignocaine for infiltration provided improved analgesia and improved the surgical field during tympanoplasty performed under monitored anesthesia care.

Atrial fibrillation and multimorbidity: How to choose the perfect direct oral anticoagulant?

Atrial fibrillation is one of the most common tachyarrhythmias, the prevalence of which is steadily increasing due to an increase in the proportion of the elderly population. The presence of a comorbidities in elderly patients with atrial fibrillation, increasing the risk of thromboembolic events, has a significant impact on the clinical strategy of atrial fibrillation, as well as on the choice of therapeutic tactics, especially anticoagulant therapy with proven efficacy and low risk of bleeding. One of the most common concomitant diseases in patients with atrial fibrillation are chronic kidney disease, anemia and coronary artery disease. These comorbidities in patients with atrial fibrillation not only increase the risk of stroke and/or systemic embolism, but are also accompanied by an increased risk of cardiovascular mortality, all causes mortality, and hemorrhagic events. At the same time, according to research data, about half of polymorbid patients with atrial fibrillation do not receive anticoagulant therapy, which indicates a low awareness of physicians about rational pharmacotherapy based on clinical recommendations for this cohort of patients. The drug of choice with the most studied safety profile and a high degree of efficacy in these patients is apixaban from the group of direct oral anticoagulants. Unlike vitamin K antagonists and other representatives of direct oral anticoagulants, apixaban, according to the conducted studies, is associated with a more significant reduction in the risk of thromboembolic events, and most importantly, has a lesser effect on the risks of bleeding in patients, predisposing to hemorrhagic complications, with atrial fibrillationand concomitant coronary artery disease, anemia, chronic kidney disease.

Association of P2Y12 inhibitor pretreatment strategy with short and long term ischemic and bleeding outcomes in NSTE-ACS patients

Abstract Background and Aims Oral P2Y12 inhibitors form the basis of both short and long term antiplatelet therapy in NSTE-ACS patients. While reducing thrombogenic activity and ischemic risk is the basis of routine P2Y12 inhibitor pretreatment in NSTE-ACS patients, timing of treatment became controversial as a result of studies showing routine P2Y12 inhibitor pretreatment is associated with an increased risk of bleeding. Even though routine pretreatment is no longer recommended in the ESC guidelines, the inadequacies in RCTs combining all treatment modalities have been noted. Our study aims to determine the relationship between P2Y12 inhibitor pretreatment strategy and short and long-term ischemic and bleeding events. Methods The study was designed as a single-center, prospective and observational study. 2602 patients, aged between 18 and 85, diagnosed with NSTE-ACS in accordance with ESC guidelines were included in the study. 2189 patients were administered with P2Y12 inhibitor pretreatment while 413 patients weren't. Demographic data, CVD risk factors, ECG, echocardiography and laboratory findings at the time of admission, interventional procedural details, type of antiplatelet and anticoagulant treatment and application time were recorded. Patients were divided into two groups as pretreatment and no-pretreatment according to the time of administration of P2Y12 inhibitor loading dose. In the no-pretreatment group choice of P2Y12 inhibitor was left to operator in the cath lab before proceeding to PCI. Post-procedural in-hospital and long term follow up (1 year) were obtained through hospital and national registry systems and patient survey. Results In the no-pretreatment group 91.3% of patients underwent coronary angiography and PCI was performed in 51.8%. In patients proceeding to PCI, 58.5% were given clopidogrel and 41.5% were given a potent P2Y12 inhibitor. In the pretreatment group, clopidogrel was the drug of choice in 93.8% of patients. In the pretreatment group, the primary composite endpoint (MACE and bleeding events) were more common during in-hospital follow-up and this difference was due to a significant increase in both BARC class I &amp; II and class III, IV &amp; V bleedings (Table 1). In the long-term follow up, statistically significant difference was only seen in BARC class I &amp; II bleedings in the pretreatment group. There were no difference in MACE rates in neither in-hospital or long-term follow up (Table 2). Also in multivariate regression analysis, pretreatment with a P2Y12 inhibitor was found to be an independent predictor of short term primary composite endpoints and long-term all-cause mortality. Conclusion The results of our study investigating the effects of the P2Y12 inhibitor pretreatment strategy on ischemic and bleeding endpoints in NSTE-ACS patients showed that the pretreatment strategy did not lead to an improvement in MACE rates in in-hospital and long-term follow-up but caused on overall increase in bleeding events.Kaplan-Meier Survival Analysis

Analysis of safety and outcome of use of NOAC in intracardiac thrombi over warfarin

Abstract Introduction Intracardiac clots occur in 15- 25% of patients post myocardial infarction and in patient with atrial fibrillation. It holds poor outcome if not treated with anticoagulation. Warfarin remains the drug of choice in such patients, however recently according to the newly published data, the European Society of Cardiology (ESC) has recommended non-vitamin K antagonist anticoagulant (NOAC) for intracardiac clots as a class 2A recommendation. There is no documented data in the region of the gulf regarding the use of NOAC in intracardiac clots. Aim We aim in this study to evaluate the use of NOAC in the treatment of intracardiac clots over warfarin, by studying the effectiveness, safety and associated complications. Methodology A retrospective cohort study from April 2017 to December 2023 was conducted of patient’s above 18 years old who have a documented intracardiac clot on echocardiography. The patient were grouped into patients discharged on NOAC and those discharged on warfarin. The participants were studied for resolution of clot and development of complication; death, bleeding and thrombosis. Results A total of 253 patients fulfilled the inclusion criteria. Out of which 45 ( 18%) patients were discharged on NOAC and 208 (82%) on warfarin. The two groups had similar demographics with equally mean age of 71 years old , 89% being males, 38% hypertensive and most common clot in the left ventricle in both groups. From those patients with documented follow up ( NOAC 45% average of 8 months, Warfarin 62% average of 7 months); 48% in the NOAC group had a documented resolution of the clot while 44% in the warfarin group had a documented resolution of the intracardiac clot.(p value of 0.7) The median resolution time in the NOAC group was 4 months while in the warfarin group 3.5 months. Bleeding occurred in 19% and mortality rate was 5% in NOAC group, while in the warfarin group 10% developed bleeding and mortality rate was 6%. Conclusion Our data pointed out the safety of NOAC as a reasonable alternative to warfarin inpatient with intracardiac clots emphasizing the ESC recommendation in this regards. We recommend a randomized studies to prove the superiority of NOAC as anticoagulation of choice in intracardiac thrombi.

Non-steroid anti-inflammatory drugs: recommendations and precautions for safe use in a multidisciplinary surgical department

Aim of the study. Conducting a safety analysis of the use of non-steroidal anti-inflammatory drugs in order to develop informed recommendations and precautions for medical practice.Materials and methods. A retrospective analysis of inpatient medical records of 250 patients in the multidisciplinary surgery department was conducted for the period from December 2023 to February 2024.Results and discussion. Based on the results of the analysis of inpatient medical records, such criteria as the presence of indications for the prescription of non-steroidal anti-inflammatory drugs (according to the diagnosis, clinical pain syndrome and according to pain assessment scales), compliance of the choice of non-steroidal anti-inflammatory drugs with national protocols/international recommendations, compliance with age, the patient's physiological/ pathological condition and allergy history for the prescription of non-steroidal anti-inflammatory drugs were 100%. The indicator for compliance of a single therapeutic dose, route of administration, frequency, duration and an appropriate diluent of non-steroidal anti-inflammatory drugs with instructions for use was 86%, where medication errors were mainly made in the frequency of use of drugs. The percentage of polypharmacy was 20%. The criterion for assessing drug-drug interactions between drugs taken by patients showed that interactions of high clinical significance (major) were 8%, while those of moderate clinical significance (moderate) were 40%.Conclusions. Nonsteroidal anti-inflammatory drugs are convenient and affordable drugs that are widely used in the treatment of diseases of various organs and systems. Therefore, to ensure the rational and safe use of drugs in this group, it is necessary to introduce effective recommendations and precautions:1. Timely completion of pain assessment scales and diary records in the Damumed medical information system;2. Development in the Damumed medical information system of divisions of appointments into planned and pro re nata (as necessary), introduction into the system of accurately recording the time of execution of doctors’ prescriptions by nursing staff for strict compliance with the intervals between doses of non-steroidal anti-inflammatory drugs allowed by the instructions.3. Introduction into the practice of doctors the use of tools to combat polypharmacy in patients ≥65 years old: Beers criteria;4. Conducting educational activities, covering both medical personnel and patients, in order to increase the level of registration of unwanted adverse reactions.

Клинико-эпидемиологические особенности системной красной волчанки у детей: данные наблюдений ГБУЗ “Морозовская ДГКБ ДЗМ”

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease of unknown etiology characterized by hyperproduction of autoantibodies. The problems of timely diagnosis and identification of predictors of an unfavorable outcome of SLE are relevant due to the variable clinical picture and a high risk of 5-year mortality in the absence of treatment. The purposes of this research were to assess the frequency of various variants of SLE onset, to identify trigger factors contributing to the development of the disease and to analyze the degree of disease activity in children. Materials and methods used: a single-center cohort retrospective study was conducted involving patients aged 9 to 17 y/o who had undergone inpatient treatment at the rheumatological department of the Morozov Children’s City Clinical Hospital (Moscow, Russia) in 2020-2023, specifying age, gender, assessing the frequency of observed symptoms of SLE onset, disease activity according to the SLEDAI scale, laboratory parameters and drug treatment. Results: total of 45 records were analyzed: 75.5% (34) girls/24.5% (11) boys; median age 15 [13; 15] y/o; most frequent clinical syndrome was cutaneous (75.5%); kidney damage was noted in 40% of cases. 86.6% had hematological disorders as follows: thrombocytopenia and leukopenia (48.9%), anemia (46.6%): Coombs-positive anemia (71.4%), lymphopenia (37.7%) and increased ESR (66.6%). Antinuclear factor (ANF Hep2) was detected in all cases. According to the SLEDAI-2K scale, the median disease activity was 11 [7; 16] points. Low disease activity (less than 6 points) was observed in 4.4% (2), average (6 to 10 points) in 44.4% (20), high (11 to 19 points) in 37.7% (17), above average (over 20 points) in 13.3% (6). Moreover, disease activity was higher in girls (p=0.940) and a relationship was found between the time required for diagnosis and disease activity according to the SLEDAI-2K scale (p=0.206). Drug therapy: glucocorticoids (GCS) orally in all cases, intravenous pulse GCS therapy in 71.0%. Hydroxychloroquine therapy was prescribed in 100.0%, mycophenolate mofetil in 57.7%, intravenous immunoglobulin in 37.7%, cyclophosphamide in 13.3%, methotrexate in 6.6%, biological therapy in 31.0%, the drug of choice was rituximab. Conclusion: updating the data on the frequency of various variants of SLE debut as well as identifying the new trigger factors contributing to the development of the disease are necessary steps aiming to increasing the awareness of the SLE course with its debut in childhood, optimizing the diagnosis process and reducing the risk for complications.