Comparison of clinical safety between standard versus extended interval dosing of immune checkpoint inhibitors: a real-world retrospective cohort study.

BACKGROUND: Extended interval dosing (ED) for inhibitors of programmed cell death protein 1 (anti-PD-1) (nivolumab, pembrolizumab) or its ligand (anti-PD-L1) (durvalumab) were recently approved based on pharmacokinetic model results that predicted a benefit-risk profile comparable with the standard dosing (SD) regimen. However, safety data in real-world condition of use are lacking. The objective was to compare the incidence and the risk factors of serious immune-related adverse events (irAEs) and any-grade irAEs between the SD and ED regimens in patients treated with anti-PD-1 or anti-PD-L1. MATERIALS AND METHODS: IrAEs were assessed from medical records in all new users of nivolumab, pembrolizumab, or durvalumab between 1 January 2019 and 31 December 2020 across two oncology centers in France. The incidence of irAEs was compared between both dosing regimens using Cox proportional hazards models adjusting for the main available confounders. RESULTS: Among 686 patients included, 63% were new users of an SD regimen, 14% of ED regimen, and 23% started with SD and switched to ED regimen during follow-up. Overall, 34.6% of patients experienced at least one irAE of any grade and 11.4% presented at least one serious grade ≥3 irAE. No statistical difference was found between the SD and ED regimen on the risk of grade ≥3 irAEs [adjusted hazard ratio (HR) 1.40, 95% confidence interval (CI) 0.71-2.76] but our results suggest an increased risk of any-grade irAEs with the ED regimen (adjusted HR 1.46, 95% CI 1.00-2.12, P = 0.048). IrAEs resolved without sequelae in 46.4% of cases, and they were fatal for three patients (0.4%). Autoimmune pre-existing condition was confirmed as a risk factor for grade ≥3 irAEs (HR 2.56, 95% CI 1.53-4.27) and for all-grade irAEs (HR 1.60, 95% CI 1.17-2.20). CONCLUSIONS: In a real-world setting, according to the regimen chosen by the oncologist based on clinical characteristics, we did not observe an increase in grade ≥3 irAE incidence between the SD and ED regimens.

[Which patient for TAVI in 2019?] / À quel patient proposer un TAVI en 2019 ?

The therapeutic management of aortic stenosis has been drastically changed by the advent of percutaneous valve replacement (TAVI). Since the first implantation, the indications have progressively been extended from the inoperable patient to the patient at low surgical risk. The main objective of this review is to describe the currently recommended main indications of TAVI depending on an individualized assessment of each patient's risk, technical characteristics and anatomical valvular criteria.

[Cognitive decline in geriatric oncology: Trends, evaluation and treatment]. / Cancer de la personne âgée : rechercher, évaluer et prendre en charge le déclin cognitif.

Cancer prevalence increases with aging. Prevalent or incident neurocognitive disorders are frequent in geriatric oncology. Cognitive decline associated with cancer increases the risk of under or over-cancer treatment and makes therapeutic decisions complex. In this context, we present tools to optimize cognitive impairment screening, identification of underlying mechanisms and specific treatments. Geriatric specialists intervention can help global care, social services utilization and patient's orientation when ambulatory cares become difficult.

Construction and validation of a photographic guide for assessing severity of chronic hand dermatitis.

BACKGROUND: A standardized instrument is needed to rate the overall severity of chronic hand dermatitis (CHD), in particular during clinical trials. OBJECTIVES: To design and validate a photographic guide. METHODS: Initially, five experts were asked to grade 50 photographs of CHD, first individually, then as a consensus-building group, in order to select the photographs included in the guide. Then, a validation session with 11 different dermatologists evaluating 28 patients was conducted to assess the interrater reliability and test-retest reproducibility of the assessment of disease severity, relying on the photographic guide, on two consecutive days. Patient order was randomized, and only diseased hands were visible to prevent any bias in evaluation. RESULTS: The experts reached a consensus for development of a photographic guide composed of five severity levels and four photographs per severity level. Results of the validation session showed a high level of interrater reliability and test-retest reproducibility. CONCLUSIONS: The photographic guide is a reliable tool for assessing the morphological severity of hand dermatitis, and can be used as part of a comprehensive evaluation of disease in international multicentre clinical trials.

[Uterine phlebography in pelvic venous stasis]. / Hystérophlébographie dans la stase veineuse pelvienne.

Pelvic veins opacification is very helpful in the diagnosis of vascular pelvic pain. First applied to intrauterine vascularisation and hypoplasia research, hysterophlebography allow the venous side of stasis to be obvious. 1) Normally, a fine intra-parietal network draining in intrauterine peripheric vein (arcuate network) is patterned by the contrast medium. For that 4 vessels roots are leaving: 2 lumbo-ovarian pedicles joining uterine venous side und tubal veins and extending over lumbo-ovarian pedicle; 2 uterine pedicles resulting from 2 uterine veins and receiving vesical veins located in the base of broad ligament. Contrast medium empties very quickly and almost the whole uterus emptying is lasting less than 10 seconds. 2) From a pathological point of view: a) in stasis, intrauterine veins pattern features are: intra-parenchymatous pictures of dilated venous network, local alterations pictures often secondary to thrombosis (9/10 on the left side) with intra-parenchymatous stasis and oblique anastomatic main vessels characterizing uterine veins thrombosis, more than 20 seconds emptying delay. Hysterographic and phlebographic times take advantage to be paired by visualizing mucous lesions (hypoplasia and polyp. endocervical and corporeal) in intra-parenchymatous stasis phenomena. b) Extrauterine stasis signs are characterized by preferentially right pedicles dilatation. Standing in upright position enhances stasis (proclive radiographies at 70 degrees). Dilatation is particularly located at the base of the broad ligament and gives to uterine veins with wide smeets a flexuous feature with wide contasted clusters. Hence here emptying is slow and belayed.

[Uterine phlebography in pelvic venous stasis]. / Hystérophlébographie dans la stase veineuse pelvienne.

Pelvic veins opacification is very helpful in the diagnosis of vascular pelvic pain. First applied to intrauterine vascularisation and hypoplasia research, hysterophlebography allow the venous side of stasis to be obvious. 1) Normally, a fine intra-parietal network draining in intrauterine peripheric vein (arcuate network) is patterned by the contrast medium. For that 4 vessels roots are leaving: 2 lumbo-ovarian pedicles joining uterine venous side und tubal veins and extending over lumbo-ovarian pedicle; 2 uterine pedicles resulting from 2 uterine veins and receiving vesical veins located in the base of broad ligament. Contrast medium empties very quickly and almost the whole uterus emptying is lasting less than 10 seconds. 2) From a pathological point of view: a) in stasis, intrauterine veins pattern features are: intra-parenchymatous pictures of dilated venous network, local alterations pictures often secondary to thrombosis (9/10 on the left side) with intra-parenchymatous stasis and oblique anastomatic main vessels characterizing uterine veins thrombosis, more than 20 seconds emptying delay. Hysterographic and phlebographic times take advantage to be paired by visualizing mucous lesions (hypoplasia and polyp. endocervical and corporeal) in intra-parenchymatous stasis phenomena. b) Extrauterine stasis signs are characterized by preferentially right pedicles dilatation. Standing in upright position enhances stasis (proclive radiographies at 70 degrees). Dilatation is particularly located at the base of the broad ligament and gives to uterine veins with wide smeets a flexuous feature with wide contrasted clusters. Hence here emptying is slow and belayed.

[Standardization of a modular and hierarchic cognitive evaluation scale applicable to dementia. A French version of the Hierarchic Dementia Scale]. / Etalonnage d'une échelle d'évaluation cognitive de structure modulaire et hiérarchisée applicable aux démences. Version française modifiée de la Hierarchic Dementia Scale.

We tested a revised version of the Hierarchic Dementia Scale (HDS), proposed by Cole and Dastoor (1980), in order to improve its clinical usefulness and to enrich our knowledge about ageing. The scale was built with 20 subtests which covered the entire range of cognitive and motor functions. Each subtest was hierarchically organized so that success in a item implied success in inferior items. This hierarchical principle was time-saving and was validated by Cole and Dastoor. 149 control subjects performed this test. They were equally divided in 4 age-groups (55-64, 65-74, 75-84, 85-97) and 2 educational levels. None of these subjects had previous history of somatic or neuropsychiatric disease. They were completely self-sufficient in daily life. A large part of the controls failed in the most difficult items of some subtests: Learning, Calculation, Mental Control, Drawing, Recall, Similarities, Constructional Praxis. For these subtests, significantly different mean-scores were observed between age-groups and educational levels. However, the influence of each factor was variable from one subtest to another. Moreover, subgroups seem to exist in our population according to specific difficulties in some of these subtests. This study calls for caution in the interpretation of results in demented patients. Comparisons with other psychometric tools remain to be performed. This scale seems to be more useful for the quantification and follow-up of cognitive deficits than for the early diagnosis of dementia. In addition, this scale, which briefly explores many aspects of cognitive functions, seems especially useful to approach the heterogeneity of DAT.

[The adolescent and contraception: psychological factors]. / L'adolescente et la contraception: aspects psychologiques

PIP: Psychological aspects of contraception in adolescence tend to be of interest primarily because of the belief that better understanding of psychological resistence to contraception would lead to more effective use and a lower rate of pregnancy. The failure of adolescents to use contraception appears to be due in part to irresponsibility but in part also to a variety of other factors. There is no ideal contraceptive for adolescents. The pill has potentially serious side effects whose significance may be exaggerated by adolescents, and the price of the contraceptive sponge may be prohibitive. Contraceptives themselves are perceived by adolescents as belonging more to parents, physicians, or the media than to themselves. Low-dose pills considered appropriate for adolescents are often abandoned because of their annoying minor side effects. Most adolescents do not seek contraception in an independent way, but out of fear that they are already pregnant or, if they have been sexually active for some time without using contraception, out of fear of infertility. Use of contraception may also be initiated by the partner, or the mother wishing to protect her daughter against pregnancy or to regularize the menstrual cycle. Contraceptive use by adolescents is complex because it signifies delaying rather than spacing or terminating pregnancy. The long duration of use that may be required until the time is right for pregnancy and the need to foresee future consequences are difficult given the cognitive level of adolescents. There are also difficult problems of access, prescription, and follow-up. Prescription of contraceptives for an adolescent is likely to invoke ambivalent feelings. Follow-up should be scheduled at fairly short intervals because of the fragility of motivation for contraceptive use at this age. The constraints of contraceptive use are not adapted to the sporadic and unplanned nature of much adolescent sexual activity. Society has an image of the adolescent as preoccupied with sexuality, but in fact adolescents are seeking to know and understand the new realities of their identity in a process in which the sexual quest plays only a secondary part. In order to improve the contraceptive performance of adolescents, a 3rd party other than a parent is needed to interact in a complementary way with the adolescent and to allow the adolescent to be heard. The objective of the interaction should not be to avoid abortion but to work to replace the rigid complementary interaction of adolescents with parents and other authority figures with a symmetrical model of communication open to the search for identity.^ieng

[Crossed aphasia in right-handed patients. II. Neuropsychological and neurolinguistic study of a case. Evolution over a 2 year period]. / Aphasie croisée chez les droitiers. II. Etude neurolinguistique et neuropsychologique d'un cas. Evolution sur deux ans.

We present an unusual case of crossed aphasia in a doctor who is totally right handed, following an infarction which almost completely destroyed his right hemisphere. The observations--linguistic and extra linguistic--during a study over two years are presented. The aphasia evolved in three stages, taking semiological and evolutive aspects not commonly met with. In speech and writing there were: 1. an oral agrammatism and a written dyssyntaxia in the initial stage; 2. the evolution of a non-fluent speech typically agrammatic leading to a jargonaphasia; 3. a dissociation between oral and written language, characterised by phonemic paraphasias in speech and dyssyntaxia in writing. Comprehension was good except for a verbal class called "empty signs" of language, in which the lexic which refers to the notion of space and time has a primary role. On an extra linguistic level some of the usual signs of right hemisphere lesions were present indicating disturbances of a spatial type. The patient could no longer grasp the concept of numerical value and showed severe difficulties in relation to time. On a linguistic level, the discussion is first considered from a typological point of view; this allows to compare our patient's disorders with a Broca's then with a conduction aphasia, Secondly, the discussion is considered from a semiological point of view, taking into consideration the 10 selected cases in the literature and adding our own; a semiological formula of crossed aphasia is given: agrammatism and/or dyssyntaxia + phonemic paraphasia and/or dysorthographia. A suggestion concerning the role of each hemisphere in the language of our patient is proposed: the possible role played by a congenital deafness in the right ear (discovered in the patient at the age of 8) to explain this abnormal hemispherical functional specialisation is discussed. Original comprehension difficulties concerning the time-space lexic are replaced by a perspective of a cognitive type. We conclude that in our patient, there was a "breakdown" of time and space which comes close to the "indifferenciation" of spatial order and time which Piaget has described in children.

[1960-1980: the resistance to contraception]. / 1960-1980: les resistences a la contraception.

PIP: Resistance to contraception, especially when badly needed, has profound psychological roots, very often unclear. The unconscious desire for a child, vis-a-vis the conscious knowledge of the problems such a child may create, plays a fundamental role in the emotional life of a woman. Men can complicate the problem; they often identify sexual potency with reproductive power, and refuse contraception for their female partners. The role of a physician in such situations is very important, very difficult and delicate. He is the one who knows, who advises, who prescribes, and who must, above all, understand. Information on contraception should be more widespread and more accurate, and every young couple should be convinced that contraception will help resolve many demographic problems, create a more responsible sexuality, improve the affective and economic situation of a family, and diminish maternal and perinatal morbidity.^ieng