Establishment of a Prognostic Prediction and Drug Selection Model for Patients with Clear Cell Renal Cell Carcinoma by Multiomics Data Analysis

Rationale. Patients with clear cell renal cell cancer (ccRCC) may have completely different treatment choices and prognoses due to the wide range of heterogeneity of the disease. However, there is a lack of effective models for risk stratification, treatment decision-making, and prognostic prediction of renal cancer patients. The aim of the present study was to establish a model to stratify ccRCC patients in terms of prognostic prediction and drug selection based on multiomics data analysis. Methods. This study was based on the multiomics data (including mRNA, lncRNA, miRNA, methylation, and WES) of 258 ccRCC patients from TCGA database. Firstly, we screened the feature values that had impact on the prognosis and obtained two subtypes. Then, we used 10 algorithms to achieve multiomics clustering and conducted pseudotiming analysis to further validate the robustness of our clustering method, based on which the two subtypes of ccRCC patients were further subtyped. Meanwhile, the immune infiltration was compared between the two subtypes, and drug sensitivity and potential drugs were analyzed. Furthermore, to analyze the heterogeneity of patients at the multiomics level, biological functions between two subtypes were compared. Finally, Boruta and PCA methods were used for dimensionality reduction and cluster analysis to construct a renal cancer risk model based on mRNA expression. Results. A prognosis predicting model of ccRCC was established by dividing patients into the high- and low-risk groups. It was found that overall survival (OS) and progression-free interval (PFI) were significantly different between the two groups ( p < 0.01 ). The area under the OS time-dependent ROC curve for 1, 3, 5, and 10 years in the training set was 0.75, 0.72, 0.71, and 0.68, respectively. Conclusion. The model could precisely predict the prognosis of ccRCC patients and may have implications for drug selection for ccRCC patients.

Experience in the use of olanzapine in an inpatient ward – clinical cases

Treating both schizophrenia and bipolar disorder require chronic drug therapy that must be chosen after careful consideration of the gains and losses associated with it. Hence, the process of the drug selection must take into account both the profile of patient’s symptoms and his coexisting diseases as well as the patient’s tolerance of earlier therapies. Olanzapine reduces positive symptoms of psychosis and enables stabilization in terms of affective episodes via blocking dopaminergic receptors. An important problem related to olanzapine therapy is its negative effect on the metabolism of carbohydrates and lipids. For this reason, appropriate information for the patient and implementation of appropriate prophylaxis, including monitoring of metabolic parameters, are recommended. Despite the risk of metabolic complications in some patients, olanzapine remains at the forefront of antipsychotic drugs, due to the good balance of benefits and losses associated with pharmacotherapy. In this paper, we present two clinical cases of patients who have been treated with olanzapine for schizophrenia and bipolar disorder.

Analisis Potensi Interaksi Obat Pada Resep Spesialis Penyakit Kulit di Salah Satu Klinik di Yogyakarta

Skin diseases often occur in tropical countries, including Indonesia. Data from the Yogyakarta City Health Office showed that skin diseases were included in the top 10 diseases at the Yogyakarta City Health Center in 2020. Various types of drugs for the treatment of skin diseases, ranging from tablets, ointments, creams, pulvis and shampoos. One of the accuracy in drug selection is to avoid drug interactions. Drug-drug interaction (DDI) occurs when two or more drugs can interact in a way that affects the effectiveness of the drug. The purpose of this study is to determine the number and categories of drug interactions. This research was carried out retrospectively by taking medical data on skin diseases at one of the skin and genital clinics in the city of Yogyakarta. The data collection period is for 2 months, namely September and October 2020. The data taken are in the form of demographic data and drug use. The results showed that there were 33 cases of minor interactions. There were 21 cases of loratadine and steroids, 2 cases of ketoconazole and steroid interactions, and 10 cases of cefadroxil and acyclovir interactions. The conclusion is that offering drug combinations that allow drug interactions to occur can avoid drug combinations taken simultaneously and use only in special circumstances. It is recommended that pharmacists provide information on the rules for taking medication to maximize the effectiveness of the drug in curing the patient's illness.

Beyondcell: targeting cancer therapeutic heterogeneity in single-cell RNA-seq data

We present Beyondcell, a computational methodology for identifying tumour cell subpopulations with distinct drug responses in single-cell RNA-seq data and proposing cancer-specific treatments. Our method calculates an enrichment score in a collection of drug signatures, delineating therapeutic clusters (TCs) within cellular populations. Additionally, Beyondcell determines the therapeutic differences among cell populations and generates a prioritised sensitivity-based ranking in order to guide drug selection. We performed Beyondcell analysis in five single-cell datasets and demonstrated that TCs can be exploited to target malignant cells both in cancer cell lines and tumour patients. Beyondcell is available at: https://gitlab.com/bu_cnio/beyondcell.

A Case of Nasal Mucosa Cautery With Reintubation Under Pharyngeal Suction for Massive Epistaxis After Extubation

We describe a case of massive epistaxis that occurred after removal of a nasal endotracheal tube, prompting emergent reintubation. Mask ventilation could not be performed because the nasal cavity was packed with gauze and the airway was being evacuated with a suction catheter. Therefore, instead of inhalational anesthetics and muscle relaxants, boluses of midazolam and remifentanil were administered, and reintubation was promptly performed. Sedation was maintained with dexmedetomidine infusion and midazolam. Nasal cautery was performed near the left sphenopalatine foramen. The patient was extubated without agitation or additional hemorrhage. Immediate recognition of the potential for airway loss, sufficient control of active bleeding, and drug selection in accordance with the emergent circumstances enabled prompt resecuring of the airway without pulmonary aspiration of blood.

Dyspepsia Drug Use Pattern of Outpatients in a Public Health Center in Batununggal District Bandung

Dyspepsia is a condition of pain in the epigastrium and a burning sensation that radiates to the chest. Dyspepsia occupies the 10th position in the 20 largest non-communicable diseases in a Public Health Center in Bandung. The heterogeneous symptoms and the absence of specific treatments can lead to irrational treatment. The research objective is to determine the pattern of drug use in patients with dyspepsia, including the right indication, the proper drug selection, the correct dose, and the proper interval of administration in a Public Health Center in Batununggal District Bandung. This study was an observational study using a cross-sectional study design that was descriptive in nature. The sampling technique employed the purposive sampling method retrospectively. The research was conducted on 104 patients diagnosed with dyspepsia with comorbidities and receiving drugs at an Outpatient Clinic in a Public Health Center in Batununggal District Bandung from January-March 2020. There were 38 male patients (36.538%) and 66 female patients (63.462%). The majority of patients were aged 56-65 years (28.846%). The most used drug class was antacids (60.448%), and the dosage form that was mostly used was tablets (40.299%). The most used single drug was antacids (51.923%), while the most used drug combination was antacids and omeprazole (23.077%). The accuracy of drug selection and the accuracy of indications were 100% correct, the accuracy of the dosage was 59.62% correct, the accuracy of the time interval for drug administration was 71% correct, and the accuracy of the duration of drug administration was 9.62% correct.

Optimizing bulk segregant analysis of drug resistance using Plasmodium falciparum genetic crosses conducted in humanized mice

Background: Classical genetic crosses in malaria parasites involve isolation, genotyping, and phenotyping of multiple progeny parasites, which is time consuming and laborious. Bulk segregant analysis (BSA) offers a powerful and efficient alternative to identify loci underlying complex traits in the human malaria parasite, Plasmodium falciparum. Methods: We have used BSA, which combines genetic crosses using humanized mice with pooled sequencing of progeny populations to measure changes in allele frequency following selection with antimalarial drugs. We used dihydroartemisinin (DHA) drug selection in two genetic crosses (Mal31xKH004 and NF54xNHP1337). We specifically investigated how synchronization, cryopreservation, and the drug selection regimen of progeny pools impacted the success of BSA experiments. Findings: We detected a strong and repeatable quantitative trait locus (QTL) at chr13 kelch13 locus in both crosses, but did not detect QTLs at ferredoxin (fd), the apicoplast ribosomal protein S10 (arps10), multidrug resistance protein 2 (mdr2). QTLs were detected using synchronized, but not unsynchronized pools, consistent with the stage-specific action of DHA. We also successfully applied BSA to cryopreserved progeny pools. Interpretation: Our results provide proof-of-principal of the utility of BSA for rapid, robust genetic mapping of drug resistance loci. Use of cryopreserved progeny pools expands the utility of BSA because we can conduct experiments using archived progeny pools from previous genetic crosses. BSA provides a powerful approach that complements traditional QTL methods for investigating the genetic architecture of resistance to antimalarials, and to reveal new or accessory loci contributing to artemisinin resistance.

A retrospective study on the evaluation of the appropriateness of oral anticoagulant therapy for patients with atrial fibrillation

Background The incidence of atrial fibrillation (AF) is increasing, and effective anticoagulation therapy can prevent adverse events. Selecting the appropriate OAC based on patient characteristics has become a challenge. Interventions are going to be a potential area of focus. Objectives To explore the discrepancies between clinician prescriptions and recommended guidelines of oral anticoagulants (OACs) for patients with atrial fibrillation (AF), and to provide direction for improving anticoagulation strategies for treating patients with AF. Materials and methods Data were collected from the electronic medical record system of Fuwai Yunnan Cardiovascular Hospital between July 2019 and January 2020. The suitability of prescribed OACs for patients with AF was assessed according to the Rules for Avoiding Prescription Inappropriateness, the prescribed medicine label, and any relevant antithrombotic guidelines for treating patients with AF. Results A total of 460 patients met the inclusion criteria. Of these, 53.7% received an appropriate prescription and 46.3% received an inappropriate prescription. Of the patients who received inappropriate prescriptions, 15.4% were prescribed without the presenting appropriate indicators, 1.3% were prescribed inappropriate drug selection, and 29.6% were prescribed inappropriate drug doses. For patients prescribed without providing appropriate indicators, 2.2% had no indication for medication and 13.3% had an indication for medication, but not a specific OAC. For patients with inappropriate drug selection, 1, 5 patients were on rivaroxaban, dabigatran respectively. The distribution of NOAC doses was as follows: dabigatran standard dose (45.2%), the low dose (54.8%). Rivaroxaban standard dose (58.9%), low dose (36.8%), high dose (4.3%). A total of 44 patients (9.6%) experienced bleeding events, 12 patients (2.6%) experienced embolic events, and 7 patients experienced other adverse events after dosing. Conclusions In clinical practice, it is common for patients with AF to receive inappropriate prescriptions of OACs. Therefore there is a need to enhance anticoagulation management in patients with AF to improve the appropriate use of OACs.