Reintroduction of immune-checkpoint inhibitors after immune-related meningitis: a case series of melanoma patients.

Immune-checkpoint inhibitors (ICIs) targeting cytotoxic T lymphocyte-associated antigen-4 and programmed cell death ligand-1) are associated with several immune-related neurological disorders. Cases of meningitis related to ICIs are poorly described in literature and probably underestimated. Several guidelines are available for the acute management of these adverse events, but the safety of resuming ICIs in these patients remains unclear. We conducted a retrospective case series of immune-related meningitis associated with ICIs that occurred between October 1 2015 and October 31 2019 in two centers: Saint-Louis and Cochin hospitals, Paris, France. Diagnosis was defined by a (1) high count of lymphocytes (>8 cells/mm3) and/or high level of proteins (>0.45 g/L) without bacteria/virus or tumor cells detection, in cerebrospinal fluid and (2) normal brain and spine imaging. Patients were followed-up for at least 6 months from the meningitis onset. Seven cases of immune-related meningitis are here reported. Median delay of meningitis occurrence after ICIs onset was 9 days. Steroid treatment was introduced in four patients at a dose of 1 mg/kg (prednisone), allowing a complete recovery within 2 weeks. The other three patients spontaneously improved within 3 weeks. Given the favorable outcome, ICIs were reintroduced in all patients. The rechallenge was well tolerated and no patients experienced meningitis recurrence. In conclusion, in our series, the clinical course was favorable and steroids were not always required. Resuming ICIs in these patients appeared safe and can thus be considered in case of isolated meningitis. However, a careful analysis of the risk/benefit ratio should be done on a case-by-case basis.

Mapping French people and health professionals' positions regarding the circumstances of morphine use to relieve cancer pain.

BACKGROUND: Cancer patients suffer in part because some health professionals prescribe or administer amounts of analgesics, namely opioids, which are too small or too widely spaced to be fully effective. Patients' reluctance to use opioids for pain treatment is often mentioned as a reason not to apply the official guidelines, but very few studies have been conducted on people's attitudes about opioid use to relieve cancer pain. METHODS: One hundred twenty lay participants and 30 health professionals (7 physicians and 23 nurses) were presented with a set of vignettes describing a terminally ill woman with cancer who is in pain. The vignettes were composed according to a four within-subject factor design: (a) level of pain reported by the patient, (b) patient's explicit request for additional administration of analgesics, (c) the physicians' final decision (e.g., to use a stronger analgesic combining paracetamol and codeine), and (d) the way the decision was made (collectively or not). Participants were asked to assess the extent to which the physician's decision was, in their view, acceptable. RESULTS: Seven qualitatively different positions were found among participants. They were called as follows: tend to disagree with any decision (9%), increase the strength of the painkiller in any case (16%), give morphine preferentially (9%), partly depends on pain level (23%), fully depends on pain level (6%), depends on decision process and on pain level (22%), and tend not to disagree with any collective decision (25%). CONCLUSIONS: Overall, 91% of participants agreed with the use of morphine in terminally ill cancer patients when the pain level was high (score of 7) and the decision to increase the strength of the painkiller was taken collectively. This percentage dropped to 69% when the team was not involved in the decision and to 40% when the pain level was lower (score of 4). If opposition to the use of morphine exists, it is not opposition to morphine itself but opposition to the circumstances of its use.

French laypeople's and health professionals' views on the acceptability of terminal sedation.

AIM: To study the views on the acceptability of terminal sedation (TS) of laypeople and health professionals in France. METHOD: In November 2013-June 2015, 223 laypeople and 53 health professionals (21 physicians and 32) judged the acceptability of TS in 48 realistic scenarios composed of all combinations of four factors: (a) the patients' life expectancy, (b) their request for sedation, (c) the decision-making process and (d) the type of sedation. In all scenarios, the patients were women with a terminal illness suffering from intractable pain and receiving the best possible care. The ratings were subjected to cluster analysis and analyses of variance. RESULTS: Five qualitatively different positions were found that were termed TS acceptable if decision taken collectively (15%), TS acceptable if patient explicitly requested it (19%), TS acceptable if patient did not explicitly oppose it (47%), 24-hour sedation not acceptable (6%) and TS always acceptable (13%). The percentage of older participants in the 'always acceptable' cluster was higher than the percentage of younger participants. CONCLUSIONS: Laypeople and health professionals do not appear to be systematically opposed to TS. The most important factors in increasing its acceptability were the patients' request for sedation and the collective character of the decision-making process.