OncoPDSS: an evidence-based clinical decision support system for oncology pharmacotherapy at the individual level.

BACKGROUND: Precision oncology pharmacotherapy relies on precise patient-specific alterations that impact drug responses. Due to rapid advances in clinical tumor sequencing, an urgent need exists for a clinical support tool that automatically interprets sequencing results based on a structured knowledge base of alteration events associated with clinical implications. RESULTS: Here, we introduced the Oncology Pharmacotherapy Decision Support System (OncoPDSS), a web server that systematically annotates the effects of alterations on drug responses. The platform integrates actionable evidence from several well-known resources, distills drug indications from anti-cancer drug labels, and extracts cancer clinical trial data from the ClinicalTrials.gov database. A therapy-centric classification strategy was used to identify potentially effective and non-effective pharmacotherapies from user-uploaded alterations of multi-omics based on integrative evidence. For each potentially effective therapy, clinical trials with faculty information were listed to help patients and their health care providers find the most suitable one. CONCLUSIONS: OncoPDSS can serve as both an integrative knowledge base on cancer precision medicine, as well as a clinical decision support system for cancer researchers and clinical oncologists. It receives multi-omics alterations as input and interprets them into pharmacotherapy-centered information, thus helping clinicians to make clinical pharmacotherapy decisions. The OncoPDSS web server is freely accessible at https://oncopdss.capitalbiobigdata.com .

Validation of Cycloserine Efficacy in Treatment of Multidrug-Resistant and Extensively Drug-Resistant Tuberculosis in Beijing, China.

Cycloserine (Cs) is recommended by the World Health Organization as a second-line drug to treat multidrug-resistant tuberculosis (MDR-TB); however, its efficacy has never been sufficiently evaluated. To gain some insights into the value of cycloserine for MDR-TB treatment, in vitro bacteriostatic effect was determined and patient validations were performed prospectively. The in vitro activity of Cs against 104 wild-type Mycobacterium tuberculosis strains was determined, and serum Cs concentrations were measured for 73 MDR TB patients 2 h after administration. The treatment outcomes for 27 MDR-TB patients who had baseline isolates and were treated with Cs-containing regimens were followed up. The MICs for 90% of the recruited 104 wild-type strains were below 32 µg/ml. Eighteen out of 52 patients had peak serum concentrations (Cmax) below 20 µg/ml at the dosage of 500 mg daily, while 13 out of 21 patients had peak serum concentrations higher than 35 µg/ml at the dosage of 750 mg daily. The percentage of favorable treatment outcomes among patients with a Cmax/MIC ratio of ≥1 was statistically significantly higher than that among the group with a Cmax/MIC ratio of <1 (P = 0.022). The epidemiological cutoff value for Cs susceptibility testing was 32 µg/ml. A high percentage of patients receiving the recommended dosage of 10 mg/kg for Cs administration could not acquire desirable blood concentrations; therefore, adjusting the dosage according to drug concentration monitoring is necessary. The Cmax/MIC ratio might be a good indicator for predicting the treatment outcome for patients with MDR-TB or extensively drug-resistant TB (XDR-TB) who are being administered Cs-containing regimens.

Performance of the MTBDRsl Line probe assay for rapid detection of resistance to second-line anti-tuberculosis drugs and ethambutol in China.

This study aimed to assess the performance of the GenoType MTBDRsl Line Probe Assay (LPA) for the detection of resistance to levofloxacin, amikacin, capreomycin and ethambutol on sputum specimens. Sputum samples from patients with smear positive multidrug-resistant tuberculosis, identified with GenoType MTBDRplus LPA, were further evaluated using the MTBDRsl LPA, while phenotypic drug susceptibility testing was used as control. Sputa with discordant outcomes were assessed by gene sequencing. 189 cases were included. The interpretability of the MTBDRsl LPA was 96.8%. The sensitivity and specificity of the MTBDRsl test were 82.5% and 91.5% for levofloxacin, 52.6% and 99.2% for amikacin, 58.1% and 97.7% for capreomycin, and 70.8% and 93.3% for ethambutol respectively. For the diagnosis of extensively drug-resistant tuberculosis, the sensitivity and specificity were 56.1% and 100%. The MTBDRsl LPA presents a specific screening tool to detect resistance to several key second-line anti-tuberculosis drugs and ethambutol in smear positive specimens.