Adverse Drug Effects Research Articles

Using a Patient Portal to Screen Patients for Symptoms After Starting New Medications.

Conduct systematic proactive pharmacovigilance screening for symptoms patients experienced after starting new medications using an electronic patient portal. We aimed to design and test the feasibility of the system, measure patient response rates, provide any needed support for patients experiencing potentially drug-related problems, and describe types of symptoms and problems patients report. We created an automated daily report of all new prescriptions, excluding likely non-new and various over-the-counter meds, and sent invitations via patient portal inviting patients to inquire if they had started the medication, and if "yes," inquire if they had they experienced any new symptoms that could be potential adverse drug effects. Reported symptoms were classified by clinical pharmacists using SOC MeDra taxonomy, and patients were offered follow-up and support as desired and needed. Of 11,724 included prescriptions for 9360 unique patients, 2758 (29.4%) patients responded. Of 2616 unique medication starts, patients reported at least 1 new symptom that represented a potential adverse drug reaction (ADR) in 678/2616 (25.9%). Nearly one-third of those experiencing new symptoms (30.3%) reported 2 or more new symptoms after initiating the drug. GI disorders accounted for 30% of the total reported ADRs. Systematic portal-based surveillance for potential adverse drug reactions was feasible, had higher response rates than other methods (such as automated interactive phone calling), and uncovered rates of potential ADRs (roughly 1 in 4 patients) consistent with other methods/studies.

Self-Medication “Boon or Bane!!”: A Cross-Sectional Survey of Undergraduate Medical Students

Background: Self-medication can be a boon as well as curse to mankind whose proper application can reduce the unnecessary pressure on the health care system. The focus of this study was to assess the knowledge, attitude, and self-medication practices among undergraduate (UG) medical students, who are more likely to self-medicate themselves due to their limited knowledge and easy drug availability. Methods: The study involved distributing questionnaires among undergraduate medical students at Government Medical College, using a cross-sectional approach. The data was collected in June 2022, with 360 responses analyzed. The questionnaire, consisting of 17 close-ended questions, included demographics, prevalence, indications for self-medication, commonly self-medicated drugs, patterns of self-medication, and knowledge about safety and consequences. Results: 327 students willingly participated in the study of which 164 were females and 163 were males belonging to the age group of 18-25 years. The prevalence of self-medication was found to be 75.5%. Most common indication was cold, cough & sore throat (70.4%) followed by headache (66%). Antipyretics (71.2%) and analgesics (62.3%) were most commonly used class of drugs. 84.5% students are aware about adverse effects of drugs. 74% opine that self-medication is not a good practice. Conclusion: Due to rising incidence of self-medication amongst the undergraduate medical students there is an increased risk of adverse drug effects. Thus, it is crucial to undertake measures that emphasize education and awareness, aiming to discourage self-medication among them.

A polifarmáciás idős betegek gyógyszerészi gondozásának gazdasági előnyei

The danger of polypharmacy (polypragmasia) lies in the fact that it usually affects older people who suffer from several chronic diseases and who are also less likely to medication adherence. For this reason, it is important to follow the drug therapy of these patients in the pharmacies, where feedback to general practitioners and specialists can take place in the event of a problem. For this reason, the development of pharmaceutical care is crucial. In the case of polypharmacy patients, inadequate drug therapy greatly increases the development of adverse drug effects and thus may increase mortality and morbidity indicators. Knowing the facts, it can be said that although pharmaceutical care involves additional costs, the adverse drug effects filtered out by it mean reduction in expenses.

Functional exosomes modified with chitosan effectively alleviate anthracycline-induced cardiotoxicity

Anthracyclines belong to a class of anti-tumor antibiotics, and their severe cardiotoxicity significantly limits their clinical use. Exosomes play key roles in intercellular communication, characterized by high biocompatibility and specific tissue and organ homing effects. In this study, doxorubicin, an anthracycline anticancer drug widely used in clinical chemotherapy, was selected as a model drug. To address the significant cardiotoxicity associated with doxorubicin, tumor exosomes are utilized as drug carriers. The homing effect of autologous exosomes enhances drug uptake by tumor cells and reduces cardiotoxicity. To enhance the stability of exosomes, improve therapeutic effectiveness, and reduce toxic side effects, chitosan was utilized to modify the surface of exosomes. Chitosan has a specific anti-tumor effect because it can target the CD44 receptor of tumor stem cells and interact with tumor cells through charge adsorption. Through in vitro cell experiments, in vivo pharmacokinetic experiments, and an in situ ectopic nude mouse tumor model, the study demonstrated that chitosan-modified tumor exosomes significantly alleviated the severe cardiotoxicity of doxorubicin, while also showing remarkable anti-tumor efficacy. This study introduces a novel approach to reduce the adverse side effects of anthracycline chemotherapeutic drugs and presents a highly promising nanocarrier delivery system.

Investigation of synergistic effect and mechanism of green tea extract and coffee extract on α‐amylase and α‐glucosidase inhibition

SummaryTo address the adverse effects of current hypoglycaemic drugs and the limited effect of individual extracts, this research investigated the inhibitory effect of combined green tea extract (GTE) and coffee (CE) on α‐amylase (α‐AMY) and α‐glucosidase (α‐GLU) and their inhibitory mechanisms. The inhibitory effects of single extracts and the complexes on α‐AMY and α‐GLU activities were compared by the principle of equivalence line. The results showed that the complexes had a good synergistic inhibition effect on both α‐AMY and α‐GLU at GTE: CE = 4:1 (w/w). Fluorescence spectroscopy and circular dichroism spectroscopy indicated that the complexes of GTE: CE = 4:1 (w/w) altered the secondary and tertiary structures of α‐AMY and α‐GLU more than the individual extracts, resulting in a synergistic inhibitory effect. The orthogonal experiments showed that tea polyphenols (TP) and coffee polyphenols (CP) were the main components responsible for the synergistic inhibitory effect of the two extracts.

Evaluation of the inhibitory effects of sitamaquine on Babesia infections

The treatment strategies for either human or animal babesiosis have been established and used for many years. With the rising indications of drug resistance and adverse side effects, finding effective and alternative therapies is urgently needed. Sitamaquine (SQ) is an 8-aminoquinoline that was first synthesized as a part of the collaborative anti-malarial program that led to primaquine. In this study, we evaluated the inhibitory effects of SQ on Babesia spp. in vitro and in vivo. The half-maximal inhibitory concentration (IC50) on in vitro cultured Babesia gibsoni was 8.04 ± 1.34 μM. Babesia gibsoni parasites showed degenerative morphological changes following SQ treatment. The in vivo growth inhibitory effects of SQ were evaluated in BALB/c mice infected with B. microti and atovaquone (ATV)-resistant B. microti strain. Oral administration of SQ at a dose of 20 mg/kg significantly inhibited the growth of B. microti and ATV-resistant B. microti. Meanwhile, SQ also showed inhibitory effects on the growth of B. rodhaini, a lethal rodent Babesia species. All mice infected with B. rodhaini treated with SQ survived, whereas the mice in the control group succumbed to the disease. The results obtained in this study indicate that SQ has potent inhibition effects against Babesia spp., which support SQ as a prospective alternative candidate for babesiosis treatment.

Risk of immediate postoperative fever in PFAPA patients undergoing tonsillectomy

ObjectivePeriodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome is the most common periodic fever syndrome in children. Tonsillectomy is considered a potential treatment option.A common concept is that patients with PFAPA are more likely to have postoperative fever, which might be hard to distinguish from other etiologies such as malignant hyperthermia or drug adverse effects. For this reason, many institutions require these patients to be cared for at their main center and not at satellite centers.Our objective was to evaluate the rate of immediate postoperative fever in PFAPA patients undergoing tonsillectomy. Material and methodsFollowing IRB approval (STUDY20060029), a retrospective chart review of all PFAPA patients who underwent tonsillectomy at a tertiary children's hospital between January 1st, 2013, and September 30th, 2022.The PHIS database was queried from January 1st, 2013, to June 30th, 2022, for pediatric tonsillectomy and PFAPA. ResultsSixty-one patients underwent tonsillectomy for PFAPA during the study period at our institution. Only one (1.6 %) had immediate postoperative fever. Fever episode resolution was seen in 90.25 % of patients, 41/41 (100 %) of the patients reported fever episodes pre-op, compared with 4/41 (9.75 %) post-op (McNemar's Chi-squared test, Chi2 = 37.0, p < 0.001).481,118 pediatric tonsillectomies were recorded in the PHIS database during this period, 1197 (0.25 %) were also diagnosed with PFAPA. None of the PFAPA patients had an immediate post-operative fever. ConclusionsOur results suggest there is no increased risk of immediate postoperative fever in PFAPA patients undergoing tonsillectomy.

Group 5 Pulmonary Hypertension: Multiple Systemic Diseases, Multiple Mechanisms of Pulmonary Hypertension, and Multiple Management Challenges

: Group 5 pulmonary hypertension (PH) with unclear and/or multifactorial mechanisms includes a wide variety of conditions associated with PH, and the mechanisms by which PH develops vary dramatically depending on the underlying condition. Indeed, in many group 5 conditions, such as sarcoidosis, multiple distinct drivers of PH are present concurrently in a single patient, with the predominant factor depending on the predisposing disease phenotype. For this reason, thorough diagnostic evaluation to most accurately phenotype every patient with group 5 PH is essential. Treatment of these patients should begin by fully characterizing and optimizing the management of their underlying disease, often in conjunction with disease experts. Initial targets of PH treatment include identifying and correcting factors that worsen PH, such as volume overload and hypoxemia, as well as a complete PH evaluation, searching for other undiagnosed causes of PH (e.g., congenital heart disease or chronic thromboembolic disease). Data to guide treatment with therapies specific to pulmonary arterial hypertension (PAH) are inadequate for any specific recommendations, and adverse effects in group 5 patients are common. If these therapies are considered, evaluation by a multidisciplinary team that includes a PH specialist is recommended. Factors in the selection of PAH therapies should include consideration of the dominant physiologic features of the underlying disease, the severity of hemodynamic and right ventricular abnormalities, the risk of adverse drug effects, and any known contraindications to PAH-specific medications based on the underlying condition. Vigilant monitoring following initiation of PAH-specific therapy is critical, as the clinical effects are hard to predict, and untoward events, such as uncovering pulmonary veno-occlusive disease, may occur. Collaborative care by a multidisciplinary team of experts is key to the management of this challenging patient population.

DNA/RNA heteroduplex technology with cationic oligopeptide reduces class-related adverse effects of nucleic acid drugs

Antisense oligonucleotides (ASOs) are a therapeutic modality for incurable diseases. However, systemic injection of gapmer-type ASOs causes class-related toxicities, including prolongation of activated partial thromboplastin time (aPTT) and thrombocytopenia. We previously reported that cholesterol-conjugated DNA/RNA heteroduplex oligonucleotides (Chol-HDOs) exhibit significantly enhanced gene silencing effects compared to ASOs, even in the central nervous system, through crossing the blood-brain barrier. In the present study, we initially evaluated the effect of the HDO structure on class-related toxicities. The HDO structure ameliorated the class-related toxicities associated with ASOs, but they remained to some extent. As a further antidote, we have developed artificial cationic oligopeptides, L-2,4-diaminobutanoic acid oligomers (DabOs), which bind to the phosphates in the major groove of A-type double helical structure of HDOs. DabO/Chol-HDO complex showed significantly improved aPTT prolongation and thrombocytopenia in mice while maintaining gene silencing efficacy. Moreover, the conjugation with DabOs effectively prevented cerebral infarction, a condition frequently observed in mice intravenously injected with high-dose Chol-HDO. These approaches, combining HDO technology with DabOs, offer distinct advantages over conventional strategies in reducing toxicities. Consequently, the DabO/HDO complex represents a promising platform for overcoming the class-related toxicities associated with therapeutic ASOs.

The contemporary issues related to conventional treatment of acne and the way forward

Background: People perceive acne as a minority disorder (not a major health concern), but it has a significant impact and burden on the victims. Although conventional drugs are available for its treatment, which are applied directly to the affected skin, such as azelaic acid, benzoyl peroxide, and salicylic acid etc. or formulationAcne vulgaris is a common skin condition that can have a significant impact on individuals, yet conventional treatments often come with various contemporary issues. This paper discusses the contemporary issues related to the conventional treatment of acne and explores a way forward. Acne vulgaris is a chronic inflammatory disorder of the pilosebaceous unit, with a high prevalence globally and in Nigeria. Although conventional drugs are available for treatment, there are several contemporary issues related to their usage that need to be addressed. Method: Relevant literature, including stakeholder reports and studies conducted globally and locally, were searched and reviewed to identify the contemporary issues related to conventional acne treatment. The key contemporary issues identified include economic, environmental, emotional, social, and spiritual concerns. Findings: The economic burden of costly conventional medications makes them inaccessible for many. Environmental issues arise from the use of potentially harmful chemicals that can pollute water sources and contribute to climate change. Acne can also lead to emotional distress, social stigma, and spiritual conflicts, especially due to the side effects of conventional treatments. Given the limitations of conventional treatments, the article recommends the use of scientifically-proven herbal remedies as a promising alternative strategy. Herbs such as tea tree oil, green tea, chasteberry, black seed, and spikeweed have demonstrated antibacterial, anti-inflammatory, and anti-androgenic properties that can effectively manage acne without the adverse effects of conventional drugs. Conclusion: The use of evidence-based herbal medicines offers a way forward in the treatment of acne, addressing the contemporary issues associated with conventional approaches. Further clinical research and regulatory approval are necessary to integrate these herbal remedies into conventional acne management and ensure their widespread and safe use. Novelty/Originality of this article: This study proposes an integrated acne treatment framework that combines conventional therapies with evidence-based herbal medicine. This approach addresses contemporary issues in acne treatment by considering economic, environmental, and socio-cultural aspects.

Pyrones Isolated from Annona Acutiflora Exhibit Promising Cytotoxic Effects on Cancer Cell Lines.

This work discusses the ongoing challenge of cancer, focusing on therapy issues such as chemotherapy resistance and adverse drug effects. It emphasizes the need for new anticancer agents with improved efficacy and fewer side effects, exploring natural products from plant sources. The Annonaceae family, specifically the Annona genus, is highlighted for its medicinal properties, including anti-inflammatory and anticancer effects. The study focuses on the isolation and elucidation of the substances present in Annona acutiflora leaves. The methodology involves chromatographic and spectroscopy techniques. The isolated compounds, (6S)-5'-oxohepten-1'E,3'E-dienyl)-5,6-dihydro-2H-pyran-2-one (1), (6R)-5'-oxohepten-1'Z,3'E-dienyl)-5,6-dihydro-2H-pyran-2-one (2) and (6R)-5'-oxohepten-1'Z,3'E-dienyl)-5,6-dihydro-2H-pyran-2-one (3) were investigated for cytotoxicity assays on cancer cell lines and normal cells. Results show promising cytotoxic activity, particularly with compound 3, demonstrating potential activity against oral cancer (43.18 μM), hepatocarcinoma (17.24 μM), melanoma (5.39 μM), and colon cancer (59.03 μM). The compound outperforms carboplatin in selectivity against oral cancer (S. I. 2.15) and melanoma (S. I. 17.22). The study concludes by suggesting the potential of these α-pyrones as effective and less toxic alternatives for cancer therapy.

Fentanyl versus Dexmedetomidine Infusion in Head and Neck Free Flap Surgery for Comparison of Hemodynamic Parameters and Anaesthetic Requirements: A Randomised Controlled Trial.

This prospective, double-blinded, randomized study aimed to compare the efficacy of dexmedetomidine and fentanyl infusions in maintaining hemodynamics during head and neck free flap surgery, as well as their impact on the relative amount of blood loss. Twenty patients with American Society of Anesthesiologists physical status I and II scheduled for elective head and neck free flap surgery were enrolled. The patients were randomly assigned to receive either dexmedetomidine (1µg/kg over 10min at anesthesia induction, followed by 0.2 to 0.75µg/kg per hour infusion during maintenance) or fentanyl (1 to 2µg/kg per hour infusion during maintenance). Intraoperative hemodynamic parameters, blood loss, blood transfusion requirements, surgeon satisfaction, adverse drug effects, and free flap survival up to 7 days were recorded. The dexmedetomidine group achieved a mean arterial pressure (MAP) value between 60 and 70 mmHg at multiple time points (15min, 3rd, 4th, 5th, and 6th hours), while the fentanyl group did not reach this range at any time point. The intergroup statistical analysis revealed a significant difference only at the 5th hour with (95% CI: -16.17 to -0.62) and P = 0.036. Additionally, the dexmedetomidine group exhibited lower heart rates (< 70/min) at several time points (15min, 2nd, 3rd, 4th, 5th, and 6th hours) compared to the fentanyl group. The intergroup comparison indicated a statistically significant difference only at the 3rd hour with (95% CI: -20.94 to -0.45) and P = 0.042. Dexmedetomidine can be a useful adjuvant of GA for inducing controlled hypotension and decreasing bleeding in free flap surgery of the head and neck region without any detrimental effect on the free flap survival.

Dupilumab in Patients with Atopic Dermatitis: A Multicentric, Long-Term, Real-World Portuguese Study.

Several clinical trials have established the efficacy and safety of dupilumab for treating atopic dermatitis (AD). However, literature remains scarce in reporting the long-term effectiveness, safety, and drug survival of dupilumab in real-world settings. This study aimed to describe the latter outcomes of dupilumab in patients with AD. This Portuguese, multicentric, observational, retrospective study included consecutive adult patients with AD who initiated dupilumab between January 2019 and September 2023, with a follow-up period up to 30months. Drug discontinuation and adverse effects data were used to estimate drug survival. Clinical assessments included the Eczema Area and Severity Index (EASI), pruritus numerical rating scale (NRS), and Dermatology Life Quality Index (DLQI). A total of 312 patients were included in the study, with 56.4% being male (median age of 30years, range 18-83). The 30-month drug survival rate was 82.0%. During the study period, 12.5% of the sample (n = 39 patients) discontinued treatment: 7.3% due to treatment failure, 2.9% due to safety concerns, 1.3% due to complete disease control, 0.6% due to pregnancy, and 0.3% due to lack of compliance. Adverse events not leading to drug discontinuation were noted in 25.6% of the sample (n = 80). Conjunctivitis was the most frequently reported adverse event (17%), followed by facial erythema (9%). At 30months, the mean EASI decreased significantly from 27.30 ± 11.89 at baseline to 2.92 ± 3.96 (p < 0.001), reflecting an overall improvement of 89.3%. Similarly, pruritus NRS decreased from 7.36 ± 1.90 at baseline to 1.74 ± 2.16 at month 30 (p < 0.001), improving by 76.4%, and mean DLQI changed from 18.0 ± 7.09 at baseline to 2.67 ± 3.95 at month 30 (p < 0.001), decreasing by 85.2%. This study increases our current understanding of dupilumab in real-world settings, demonstrating its long-term effectiveness and safety in treating AD.

Perfil das prescrições de fitoterápicos anabolizantes comercializados por uma farmácia magistral no Rio de Janeiro

Introduction: Since antiquity, humans have used plants for various purposes, including improving physical performance. However, in recent years, the search for herbal medicines aimed at mimicking the anabolic effect, with lower health risks and without being detected in doping control, has sparked the interest of athletes and gym users. Objective: To evaluate which herbal drugs with possible androgenic activity are prescribed as magistral formulations in the city of Rio de Janeiro. Method: Data from 10,276 prescriptions recorded in the database of a network of compounding pharmacies located in the city of Rio de Janeiro between January and December 2020 were collected and analyzed. The prescribed and dispensed formulations contained Ajuga turkestanica, Cyanotis vaga, Eurycoma longifolia, Lepidium meyenii, Mucuna pruriens, Tribulus terrestris, Trigonella foenum-graecum, and Withania somnifera. Results: Most prescriptions (57.0%) were for women, prescribed by specialists in orthomolecular medicine (38.0%), and only 4.0% of prescriptions were prescribed by nutritionists. Regarding the types of medications, 8,116 prescriptions (79.0%) were formulations of combinations of one or more anabolic herbal drugs with pharmaceuticals. M. pruriens was the most prescribed herbal drug (29.0%), with or without combination. Conclusions: Most of the prescribed plants still do not have proven efficacy and safety regarding anabolic action; therefore more clinical studies are necessary to determine the possible drug interactions and adverse effects of these herbal drugs.

Treatment Outcomes of Dipeptidyl Peptidase-4 Inhibitors and Sodium-Glucose Co-Transporter-2 Inhibitors in Diabetes Mellitus with Poor Glycemic Control

Background: Diabetes, a progressive disease necessitating multifaceted pharmacological interventions for glycemic control, commonly employs Dipeptidyl Peptidase-4 inhibitors (DPP-4i) and Sodium-Glucose Co-Transporter-2 inhibitors (SGLT-2i). The ongoing challenge lies in determining the superior option for safety and efficacy. Objective: This study aims to describe the treatment outcomes of DPP-4 inhibitors (DPP-4i) and Sodium- Glucose Co-Transporter-2 inhibitors (SGLT-2i) in individuals with diabetes mellitus (DM) receiving metformin with poor glycemic control. Methods: This prospective study was conducted at the Endocrinology Outpatient Department of Dhaka Medical College Hospital, Dhaka, and included 90 individuals with diabetes mellitus who met the selection criteria. Divided into two groups, Group I (n=45) received DPP-4 inhibitors plus metformin, and Group II (n=45) received SGLT2 inhibitors plus metformin. Baseline data, including HbA1c, fasting blood glucose (FBG), blood glucose 2 hours after breakfast, weight, lipid profile, and serum creatinine, were recorded at the first visit and 12 weeks. Safety was assessed based on adverse drug effects. Results: After 12 weeks, both groups exhibited significant reductions in HbA1c, FBG, and postprandial blood glucose levels. However, the SGLT-2i group demonstrated significant improvements in HbA1c (P&lt;0.012), fasting plasma glucose (P&lt;0.003), and postprandial glucose levels (P&lt;0.001), along with a reduction in body weight (P&lt;0.042). Hypoglycemia rates were low and balanced between groups. Notably, SGLT-2i usage correlated with an increased incidence of urinary tract infections (13.33% vs. 6.66% in DPP-4i) and exclusive genital infections (11.11%, P&lt;0.022). Conclusion: Diabetic patients receiving SGLT-2 inhibitors had better glycemic control and body weight improvements in comparison to DPP-4 inhibitors. However, SGLT-2 inhibitors encountered more genital infections than DPP-4 inhibitors. J MEDICINE 2024; 25: 107-114

Advancing medical imaging: detecting polypharmacy and adverse drug effects with Graph Convolutional Networks (GCN)

Polypharmacy involves an individual using many medications at the same time and is a frequent healthcare technique used to treat complex medical disorders. Nevertheless, it also presents substantial risks of negative medication responses and interactions. Identifying and addressing adverse effects caused by polypharmacy is crucial to ensure patient safety and improve healthcare results. This paper introduces a new method using Graph Convolutional Networks (GCN) to identify polypharmacy side effects. Our strategy involves developing a medicine interaction graph in which edges signify drug-drug intuitive predicated on pharmacological properties and hubs symbolize drugs. GCN is a well-suited profound learning procedure for graph-based representations of social information. It can be used to anticipate the probability of medicate unfavorable impacts and to memorize important representations of sedate intuitive. Tests were conducted on a huge dataset of patients’ pharmaceutical records commented on with watched medicate unfavorable impacts in arrange to approve our strategy. Execution of the GCN show, which was prepared on a subset of this dataset, was evaluated through a disarray framework. The perplexity network shows the precision with which the show categories occasions. Our discoveries demonstrate empowering advance within the recognizable proof of antagonistic responses related with polypharmaceuticals. For cardiovascular system target drugs, GCN technique achieved an accuracy of 94.12%, precision of 86.56%, F1-Score of 88.56%, AUC of 89.74% and recall of 87.92%. For respiratory system target drugs, GCN technique achieved an accuracy of 93.38%, precision of 85.64%, F1-Score of 89.79%, AUC of 91.85% and recall of 86.35%. And for nervous system target drugs, GCN technique achieved an accuracy of 95.27%, precision of 88.36%, F1-Score of 86.49%, AUC of 88.83% and recall of 84.73%. This research provides a significant contribution to pharmacovigilance by proposing a data-driven method to detect and reduce polypharmacy side effects, thereby increasing patient safety and healthcare decision-making.

Use of allopurinol to manage skewed 6-mercaptopurine metabolism in pediatric maintenance acute lymphoblastic leukemia treatment.

6-mercaptopurine is a cornerstone of maintenance therapy for pediatric ALL. Response to 6MP is typically determined by the ANC. Therapeutic ANC range while receiving 6MP is between 500 and 1500/μL. In addition to desired myelosuppression, 6MP is associated with multiple adverse drug effects. Increased doses of 6MP can lead to therapeutic ANC values; however, patients may experience adverse effects before obtaining therapeutic myelosuppression, often deemed "skewed metabolism." Allopurinol may potentially correct skewed 6MP metabolism. Pediatric patients with ALL with 6MMP and 6TGN metabolites drawn during maintenance therapy were analyzed for allopurinol use. The primary outcome evaluated the percentage of time spent in therapeutic ANC range before and after allopurinol initiation. In addition, the difference in 6MMP:6TGN ratios before and after allopurinol initiation, incidence of hepatotoxicity, and rates of relapse, were analyzed. Ninety-five patients were included for analysis. Thirty-two (34%) patients received allopurinol. There were no significant differences in baseline demographics between the patients who received allopurinol and those who did not. When comparing ANC values pre- and post-allopurinol initiation, a statistically significant increase in the percentage of time spent in therapeutic range was observed (27% vs. 43%; p = .03). In addition, when comparing metabolite ratios pre- and post-allopurinol initiation, a statistically significant decrease in 6MMP:6TGN metabolite ratio values was observed (86.7 vs. 3.6; p < .0001). Allopurinol significantly increased the percent time in therapeutic ANC range and can be safely utilized to significantly lower the ratio of 6MMP:6TGN metabolites, alleviating the undesirable side effects of 6MMP, and optimizing the anti-leukemic effects associated with 6TGN.

DIGEP-Pred 2.0: A web application for predicting drug-induced cell signaling and gene expression changes.

The analysis of drug-induced gene expression profiles (DIGEP) is widely used to estimate the potential therapeutic and adverse drug effects as well as the molecular mechanisms of drug action. However, the corresponding experimental data is absent for many existing drugs and drug-like compounds. To solve this problem, we created the DIGEP-Pred 2.0 web application, which allows predicting DIGEP and potential drug targets by structural formula of drug-like compounds. It is based on the combined use of structure-activity relationships (SARs) and network analysis. SAR models were created using PASS (Prediction of Activity Spectra for Substances) technology for data from the Comparative Toxicogenomics Database (CTD), the Connectivity Map (CMap) for the prediction of DIGEP, and PubChem and ChEMBL for the prediction of molecular mechanisms of action (MoA). Using only the structural formula of a compound, the user can obtain information on potential gene expression changes in several cell lines and drug targets, which are potential master regulators responsible for the observed DIGEP. The mean accuracy of prediction calculated by leave-one-out cross validation was 86.5 % for 13377 genes and 94.8 % for 2932 proteins (CTD data), and it was 97.9 % for 2170 MoAs. SAR models (mean accuracy-87.5 %) were also created for CMap data given on MCF7, PC3, and HL60 cell lines with different threshold values for the logarithm of fold changes: 0.5, 0.7, 1, 1.5, and 2. Additionally, the data on pathways (KEGG, Reactome), biological processes of Gene Ontology, and diseases (DisGeNet) enriched by the predicted genes, together with the estimation of target-master regulators based on OmniPath data, is also provided. DIGEP-Pred 2.0 web application is freely available at https://www.way2drug.com/digep-pred.

An update on the perioperative management of postcraniotomy pain.

Pain after craniotomy is often severe and undertreated. Providing adequate analgesia while avoiding medication adverse effects and physiological complications of pain remains a perioperative challenge. Multimodal pain management includes regional anesthesia and analgesic adjuncts. Strategies aim to reduce or eliminate opioids and the associated side effects. Many individual pharmacologic interventions have been studied with beneficial effects on acute pain following craniotomy. Evidence has been accumulating in support of scalp blockade, nonsteroidal anti-inflammatory drugs (NSAIDs), dexmedetomidine, paracetamol, and gabapentinoids. The strongest evidence supports scalp block in reducing postcraniotomy pain and opioid requirements. Improving analgesia following craniotomy continues to be a challenge that should be managed with multimodal medications and regional techniques. Additional studies are needed to identify the most effective regimen, balancing efficacy and adverse drug effects.

Efficacy and Safety of Tocilizumab with Methylprednisolone versus Methylprednisolone Only as a Treatment for Severe Covid-19 Patients

Abstract Background SARS-CoV-2 was identified as a worldwide fatal pandemic that causes acute respiratory infections. The aim of this work was to compare the effect of Using combined therapy: (tocilizumab with Methylprednisolone) versus using (Methylprednisolone alone) as immuno-modulatory therapy on 28 days mortality mortality, need for mechanical ventilation &amp; adverse effects. Methods This retrospective observational cohort study was carried out on 60 patients diagnosed as having covid 19 infection with cytokine storm and severe acute respiratory syndrome during the period(2020-2021). Patients were divided into 2 groups: (TCZ+MP)group received 2 doses of tocilizumab within 24 hrs (5 mg/kg in each dose) in addition to a dose of methylprednisolone(2mg/kg/day)for7days and(MP)group:received only a dose of methylprednisolone (2 mg\kg\day) for 7days. All patients were subjected to routine laboratory investigations (Complete blood count, liver function tests, kidney function tests, LDH, ferritin, D-dimer, frequent ABGs (P/F ratio), CRP, IL6, procalcitonin&amp; albumin), and radiology investigation (Chest x-ray and CT chest). Results 60 patients with ARDS(both genders) were included in this study, in TCZ+MPgroup, 8(26.67%) of 30 patients died, compared to 17(56,67%) of 30patients in (MP)group, so mortality rate was significantly lower in patients on TCZ+MPgroup than those on (MP)group (P value =0.018). In TCZ+MPgroup, 12(40%) of 30 patients needed mechanical ventilation compared to 22(73.33%) of 30 patients in MP group, so Number of patients who required mechanical ventilation was significantly lower in patients on TCZ+MPgroup than MP group (P value = 0.009). Adverse effects of intervention drugs after 28 days were insignificantly different between both groups (P value = 0.018). Conclusions In patients with severe COVID-19 infection, combination therapy of tocilizumab &amp;methylprednisolone reduced mortality rate and need for mechanical ventilation as compared with the use of methylprednisolone alone.