In retrospective evaluation of the adaptive escalation design, none of the cases overshot the actually reported top dose; one case resulted in a top dose that was within 20% under the estimated maximum tolerated dose in the original study. The median reduction of total number of participants per study was 38%. Trial simulations confirmed the retrospective evaluation, showing a similar performance of the adaptive escalation design compared with the conventional 6 + 2 design, at a reduced study size for compounds with a presumed acceptable therapeutic window. The adaptive escalation design was shown to make “best use” of participants in FIH studies without compromising safety.Palliative care was initially developed for patients with a cancer diagnosis and severe symptoms. Despite the ambition to broaden the palliative care approach to include other groups, patients with cancer are still a majority in specialised palliative care. The broader view and development of palliative care has led to an intense debate on existing definitions. Following a request from The Lancet Commission on global palliative care, the International Association of Hospice and Palliative Care (IAHPC) has presented a new definition. The proposal was developed in several stages, in collaboration with specialists in palliative care from a total of 88 countries. The IAHPC’s definition differs from the WHO’s definition in several aspects. Most importantly, the IAHPC’s definition takes a reversed perspective and instead of focusing on life-threatening illness as motivating palliative care, the new proposal focuses on serious suffering of a person with severe illness.Contrast induced encephalopathy (CIE) is a rare side effect to contrast media. The clinical presentation comprises cortical blindness, seizures and focal neurological aberrations. A 72-year old man with aortic stenosis underwent transcatheter aortic valve implantation (TAVI). At the end of the procedure he suffered from sudden onset of seizures. Information from the medical charts revealed information about a similar seizure nine years earlier, also in conjunction with administration of intraarterial contrast. The man recovered within one hour without sequelae. Midazolam and similar agents can be used prophylactically in future exposures to contrast media to lower the risk of recurrence.Patients normally use opioids for less than 3 days after soft tissue and simple bone surgery in the upper extremity [2], but packages of prescribed medications include many pills beyond this need. To address this, we designed a bag of painkillers to optimize pain treatment, primarily for those with long lasting brachial plexus block that may have severe pain debut at home [1]. The bag includes seven oxycodone tablets of 5 mg, and 1 day’s worth of ibuprofen and paracetamol in case patients did not buy these preoperatively as instructed. For those with long-lasting ropivacaine brachial plexus block, smart bag treatment was timed to begin 7 hours after ropivacaine initiation. Based on interviews of the first 103 patients, 78% were satisfied. Surgeons and nurses also appreciated the reduced administrative tasks and faster patient discharge.

Stress-related mucosal bleeding (SRMB) occurs in approximately 2-4% of critically ill patients. Patients with aneurysmal subarachnoid hemorrhage (aSAH) have a (diffuse) space-occupying lesion, are critically ill, often require mechanical ventilation, and frequently receive anticoagulation or antiplatelet therapy after aneurysm embolization, all of which may be risk factors for SRMB. However, no studies have evaluated SRMB in patients with aSAH. Aims of the study were to determine the incidence of SRMB in aSAH patients, evaluate the effect of acid suppression on SRMB, and identify specific risk factors for SRMB.

This was a multicenter, retrospective, observational study conducted across 17 centers. Each center reviewed up to 50 of the most recent cases of aSAH. Patients with length of stay (LOS) < 48h or active GI bleeding on admission were excluded. Variables related to demographics, aSAH severity, gastrointestinal (GI) bleeding, provision of SRMB prophylaxis, adverse events, intensive care unit (ICU),/min and the incidence of cerebral vasospasm as specific risk factors associated with GI bleeding. Cerebral vasospasm has not previously been described as a risk for GI bleeding (OR 2.5 95% CI 1.09-5.79).

Clinically important GI bleeding occurred in 4.9% of patients with aSAH, similar to the general critical care population. Risk factors associated with GI bleeding were prolonged mechanical ventilation (> 48h), creatinine clearance < 60ml/min, presence of coagulopathy, elevation of intracranial pressure, and cerebral vasospasm. Further prospective research is needed to confirm this observation within this patient population.

 48 h), creatinine clearance  less then  60 ml/min, presence of coagulopathy, elevation of intracranial pressure, and cerebral vasospasm. Further prospective research is needed to confirm this observation within this patient population.

Acute physiologic derangements and multiple organ dysfunction are common after subarachnoid hemorrhage. We aimed to evaluate the simplified acute physiology score 3 (SAPS-3) and the sequential organ failure assessment (SOFA) scores for the prediction of in-hospital mortality in a large multicenter cohort of SAH patients.

This was a retrospective analysis of prospectively collected data from 45 ICUs in Brazil, during 2014 and 2015. Patients admitted with non-traumatic subarachnoid hemorrhage (SAH) were included. Clinical and outcome data were retrieved from an electronic ICU quality registry. SAPS-3 and SOFA scores, without the neurological components (i.e., nSAPS-3 and nSOFA, respectively) were recorded, as well as the World Federation of Neurological Surgeons (WFNS) scale. see more We used multilevel logistic regression analysis to identify factors associated with in-hospital mortality. We evaluated performance using the area under the receiver operating characteristic curve (AUROC), as well as calibration belts and precision-recall plots.