In recent years, reinforcement learning (RL) has gained traction in the healthcare domain. In particular, RL methods have been explored for haemodynamic optimization of septic patients in the Intensive Care Unit. Most hospitals however, lack the data and expertise for model development, necessitating transfer of models developed using external datasets. This approach assumes model generalizability across different patient populations, the validity of which has not previously been tested. In addition, there is limited knowledge on safety and reliability. These challenges need to be addressed to further facilitate implementation of RL models in clinical practice.
 
  We developed and validated a new reinforcement learning model for hemodynamic optimization in sepsis on the MIMIC intensive care database from the USA using a dueling double deep Q network. We then transferred this model to the European AmsterdamUMCdb intensive care database. T-Distributed Stochastic Neighbor Embedding and Sequential Organ Failure previous work.
 
  We created a reinforcement learning model for optimal bedside hemodynamic management and demonstrated model transferability between populations from the USA and Europe for the first time. We proposed new methods for deep policy inspection integrating expert domain knowledge. This is expected to facilitate progression to bedside clinical decision support for the treatment of critically ill patients.
 We created a reinforcement learning model for optimal bedside hemodynamic management and demonstrated model transferability between populations from the USA and Europe for the first time. We proposed new methods for deep policy inspection integrating expert domain knowledge. This is expected to facilitate progression to bedside clinical decision support for the treatment of critically ill patients.As the population ages, patients' complexity and the scope of their care is increasing. Over 60% of the population is 65 years of age or older and suffers from multi-morbidity, which is associated with two times as many patient-physician encounters. Yet clinical practice guidelines (CPGs) are developed to treat a single disease. To reconcile these two competing issues, previously we developed a framework for mitigation, i.e., identifying and addressing adverse interactions in multi-morbid patients managed according to multiple CPGs. That framework relies on first-order logic (FOL) to represent CPGs and secondary medical knowledge and FOL theorem proving to establish valid patient management plans. In the work presented here, we leverage our earlier research and simplify the mitigation process by representing it as a planning problem using the Planning Domain Definition Language (PDDL). This new framework, called MitPlan, identifies and addresses adverse interactions using durative planning actions that embody clinical actions (including medication administration and patient testing), supports a physician-defined length of planning horizons, and optimizes plans based on patient preferences and action costs. It supports a variety of criteria when developing management plans, including the total cost of prescribed treatment and the cost of the revisions to be introduced. The solution to MitPlan's planning problem is a sequence of timed actions that are easy to interpret when creating a management plan. We demonstrate MitPlan's capabilities using illustrative and clinical case studies.
  We aimed to examine cemiplimab, a programmed cell death 1 inhibitor, in the first-line treatment of advanced non-small-cell lung cancer with programmed cell death ligand 1 (PD-L1) of at least 50%.
 
  In EMPOWER-Lung 1, a multicentre, open-label, global, phase 3 study, eligible patients recruited in 138 clinics from 24 countries (aged ≥18 years with histologically or cytologically confirmed advanced non-small-cell lung cancer, an Eastern Cooperative Oncology Group performance status of 0-1; never-smokers were ineligible) were randomly assigned (11) to cemiplimab 350 mg every 3 weeks or platinum-doublet chemotherapy. Crossover from chemotherapy to cemiplimab was allowed following disease progression. Primary endpoints were overall survival and progression-free survival per masked independent review committee. Primary endpoints were assessed in the intention-to-treat population and in a prespecified PD-L1 of at least 50% population (per US Food and Drug Administration request to the sponsor), which consisted ofdverse events occurred in 98 (28%) of 355 patients treated with cemiplimab and 135 (39%) of 342 patients treated with chemotherapy.
 
  Cemiplimab monotherapy significantly improved overall survival and progression-free survival compared with chemotherapy in patients with advanced non-small-cell lung cancer with PD-L1 of at least 50%, providing a potential new treatment option for this patient population.
 
  Regeneron Pharmaceuticals and Sanofi.
 Regeneron Pharmaceuticals and Sanofi.
  Androgen suppression is a central component of prostate cancer management but causes substantial long-term toxicity. Transdermal administration of oestradiol (tE2) circumvents first-pass hepatic metabolism and, therefore, should avoid the cardiovascular toxicity seen with oral oestrogen and the oestrogen-depletion effects seen with luteinising hormone releasing hormone agonists (LHRHa). We present long-term cardiovascular follow-up data from the Prostate Adenocarcinoma Transcutaneous Hormone (PATCH) trial programme.
 
  PATCH is a seamless phase 2/3, randomised, multicentre trial programme at 52 study sites in the UK.  https://www.selleckchem.com/products/nx-1607.html  Men with locally advanced or metastatic prostate cancer were randomly allocated (12 from August, 2007 then 11 from February, 2011) to either LHRHa according to local practice or tE2 patches (four 100 μg patches per 24 h, changed twice weekly, reducing to three patches twice weekly if castrate at 4 weeks [defined as testosterone ≤1·7 nmol/L]). Randomisation was done using a computer-based minimistments in cardiovascular mortality or morbidity. Oestrogens administered transdermally should be reconsidered for androgen suppression in the management of prostate cancer.
 
  Cancer Research UK, and Medical Research Council Clinical Trials Unit at University College London.
 Cancer Research UK, and Medical Research Council Clinical Trials Unit at University College London.