dadi.CUDA: Accelerating Population Genetics Inference with Graphics Processing Units.

dadi is a popular but computationally intensive program for inferring models of demographic history and natural selection from population genetic data. I show that running dadi on a Graphics Processing Unit can dramatically speed computation compared with the CPU implementation, with minimal user burden. Motivated by this speed increase, I also extended dadi to four- and five-population models. This functionality is available in dadi version 2.1.0, https://bitbucket.org/gutenkunstlab/dadi/.

Comparative Effectiveness, Safety, and Real-World Outcomes of a Nurse-Led, Protocol-Driven Penicillin Allergy Evaluation From the Hong Kong Drug Allergy Delabelling Initiative (HK-DADI).

BACKGROUND: There is a high prevalence of unconfirmed penicillin allergy, which is associated with a multitude of adverse clinical outcomes. With the overwhelming burden of currently incorrect labels and the lack of allergy specialist services, new delabeling strategies are urgently needed. OBJECTIVE: To assess the effectiveness, safety, and real-world outcomes of a nurse-led, protocol-driven evaluation of penicillin allergy, the Hong Kong Drug Allergy Delabelling Initiative (HK-DADI). METHODS: Adult patients with suspected penicillin allergy were recruited into HK-DADI. Allergy and postdelabeling outcomes were retrospectively compared between patients evaluated via HK-DADI or traditional allergist evaluation. RESULTS: A total of 312 completed penicillin allergy evaluation: 84 (27%) and 228 (73%) via HK-DADI and traditional pathways, respectively. Overall, 280 penicillin allergies were delabeled (90%). The delabeling rate between HK-DADI and traditional pathways was similar (90% vs 89%; P = .796). Among patients of the HK-DADI pathway, the delabeling rate was significantly higher among low-risk (LR) compared with non-LR patients (97% vs 77%; P = .010). Skin tests did not add diagnostic value among LR patients. No patients developed severe or systemic reactions during the evaluation. Upon 6- to 12-month follow-up (median, 10 months), 123 patients experienced infective episodes (44%) and 63 used penicillins again after delabeling (23%). This proportion was significantly higher in patients who were delabeled via HK-DADI compared with the traditional pathway (32% vs 19%; P = .026). CONCLUSIONS: The Hong Kong Drug Allergy Delabelling Initiative, a nurse-led, protocol-driven evaluation, was safe and effective in penicillin allergy delabeling. It led to an even higher rate of future penicillin use after delabeling and mitigated the need for unnecessary skin testing among LR patients.

Final 3-year Results of the Dasatinib Discontinuation Trial in Patients With Chronic Myeloid Leukemia Who Received Dasatinib as a Second-line Treatment.

INTRODUCTION: We previously reported an interim analysis of the DADI (dasatinib discontinuation) trial. The results showed that 48% of patients with chronic myeloid leukemia in the chronic phase who maintained a deep molecular response (DMR) for ≥ 1 year could discontinue second- or subsequent-line dasatinib treatment safely at a median follow-up of 20 months. However, the results from longer follow-up periods would be much more useful from a clinical perspective. PATIENTS AND METHODS: The DADI trial was a prospective, multicenter trial conducted in Japan. After confirming a stable DMR for ≥ 1 year, dasatinib treatment subsequent to imatinib or nilotinib was discontinued. After discontinuation, the loss of DMR (even of 1 point) was defined as stringent molecular relapse, thereby triggering therapy resumption. The predictive factors of treatment-free remission (TFR) were analyzed. RESULTS: The median follow-up period was 44.0 months (interquartile range, 40.5-48.0 months). The estimated overall TFR rate at 36 months was 44.4% (95% confidence interval, 32.0%-56.2%). Only 2 patients developed a molecular relapse after the 1-year cutoff point. The presence of imatinib resistance was a significant risk factor for molecular relapse. Moreover, high natural killer cell and low γδ+ T-cell and CD4+ regulatory T-cell (CD25+CD127low) counts before discontinuation correlated significantly with successful therapy discontinuation. CONCLUSION: These findings suggest that discontinuation of second- or subsequent-line dasatinib after a sustained DMR of ≥ 1 year is feasible, especially for patients with no history of imatinib resistance. In addition, the natural killer cell count was associated with the TFR.

New hope for chronic myelogenous leukemia patients: dasatinib offers better efficacy with shorter treatment.

Although the discovery of tyrosine kinase inhibitors (TKIs) has dramatically improved the prognoses of chronic myelogenous leukemia (CML) patients, a cure has remained elusive. Unanswered questions include how long must a patient continue on TKI therapy, and how does a patient know when he/she can safely stop or finish this therapy? Imagawa et al. have carefully addressed these questions of safety and efficacy using a stop study of the second-generation TKI dasatinib. The results of a multicenter phase II trial termed the "dasatinib discontinuation" (DADI) trial indicated that 48% (30/63) of CML patients who had maintained a deep molecular response (DMR) to second-line or subsequent dasatinib therapy for at least for 1 year did not show any signs of disease relapse. Thus, even after it is stopped, dasatinib treatment may decrease the chance of disease relapse and provide a curative benefit to CML patients. This work by Imagawa et al. strongly supports the clinical utility of the second-generation TKI dasatinib for CML treatment.