IMPORTANCE trial: a provisional study-design of a single-center, phase II, double-blinded, placebo-controlled, randomized, 4-week study to compare the efficacy and safety of intranasal esketamine in chronic opioid refractory pain.

Background:  Cancer is the second leading cause of death globally. Up to 86% of advanced cancer patients experience significant pain, while 10-20% live in chronic pain. Besides, increasing prescription of opioids resulted in 33,000 deaths in the US in 2015. Both reduce patients' functional status and quality of life. While cancer survival rates are increasing, therapeutic options for chronic opioid refractory pain are still limited. Esketamine is the s-enantiomer of ketamine, with superior analgesic effect and less psychotomimetic side effects. Intranasal esketamine was approved by the FDA for treatment-resistant depression. However, its use in chronic cancer pain has never been tested. Therefore, we propose a phase II, randomized, placebo-controlled trial to evaluate the efficacy and safety of intranasal esketamine in chronic opioid refractory cancer pain. Methods and analysis: We will recruit 120 subjects with chronic opioid refractory pain, defined as pain lasting more than 3 months despite optimal therapy with high dose opioids (>60 mg morphine equivalent dose/day) and optimal adjuvant therapy. Subjects will be randomized into two groups: intranasal esketamine (56mg) and placebo. Treatment will be administered twice a week for four consecutive weeks. The primary outcome is defined as reduction in the Numeric Pain Rating Scale (NPRS) after first application. Secondary outcomes include NPRS reduction after four weeks, the number of daily morphine rescue doses, functional status and satisfaction, and depression. Conclusion: This study may extend therapeutic options in patients with chronic pain, thus improving their quality of life and reducing opioid use. Trial registration: Clinical Trials.gov, NCT04666623. Registered on 14 December 2020.

Infection surveillance in pediatric hematopoietic stem cell transplantation recipients.

OBJECTIVE: To describe the profile of reported healthcare-associated infections (HAIs) in pediatric patients submitted to hematopoietic stem cell transplantation (HSCT) at a reference center. METHODS: Retrospective cohort of pediatric patients who were submitted to HSCT from 2008 to 2016. The criteria for HAI were based on those established by the National Healthcare Safety Network. Data were collected by active surveillance performed daily by professionals. This study was approved by the institutional research ethics committee. RESULTS: A total of 86 HSCTs were performed in 81 patients younger than 18 years of age (median, 10 years). Of these, 69 (85%) were males. Aplastic anemia and leukemia were the main diagnoses. A total of 140 HAIs were diagnosed with an incidence density of 28.2 infections/1000 patient-days. The most common HAI was laboratory-confirmed bloodstream infection (46), the majority of which was reported to be central venous catheter-associated (43). Gram-negative bacteria were the most prevalent microorganisms (58.5%). Almost all the infections occurred until 30 days after transplantation, and 17 deaths were observed within 180 days after the procedure. CONCLUSION: Active surveillance of HAIs in HSCT children allowed the evaluation of the incidence and profile of HAIs, which is essential for the health care of these patients.