Baseline circulating tumour DNA and total metabolic tumour volume as early outcome predictors in aggressive large B-cell lymphoma. A real-world 112-patient cohort.

Approximately 20%-50% of patients with large B-cell lymphoma (LBCL) experience poor outcomes. We aimed to evaluate the combined prognostic value of circulating tumour DNA (ctDNA) and total metabolic tumour volume (TMTV) in LBCL. This observational single-centre study included 112 newly diagnosed LBCL patients, receiving R-CHOP/R-CHOP-like chemotherapies. CtDNA load was calculated following next-generation sequencing of cell-free DNA (cfDNA) using a targeted 40-gene lymphopanel. TMTV was measured using a fully automated artificial intelligence-based method for lymphoma lesion segmentation. CtDNA was detected in cfDNA samples from 95 patients with a median concentration of 3.15 log haploid genome equivalents per mL. TMTV measurements were available for 102 patients. The median TMTV was 501 mL. High ctDNA load (>3.57 log hGE/mL) or high TMTV (>200 mL) were associated with shorter 1-year PFS (44% vs. 83%, p < 0.001 and 64% vs. 97%, p = 0.002, respectively). When combined, three prognostic groups were identified. The shortest PFS was observed when both TMTV and ctDNA load were high (p < 0.001). Even with a short follow up, combining ctDNA load with TMTV improved the risk stratification of patients with aggressive LBCL. In the near future, very high-risk patients could benefit from CAR T-cell therapy or bispecific antibodies as first-line treatments.

Diagnostic Performance of the 4-Item Geriatric Depression Scale for Depression Screening in Older Patients with Cancer: The ELCAPA Cohort Study.

BACKGROUND: In older patients with cancer, depression is difficult to assess because of its heterogeneous clinical expression. The 4-item version of the Geriatric Depression Scale (GDS-4) is quick and easy to administer but has not been validated in this population. The present study was designed to test the diagnostic performance of the GDS-4 in a French cohort of older patients with cancer before treatment. MATERIALS AND METHODS: Our cross-sectional analysis of data from the Elderly Cancer Patient cohort covered all patients with cancer aged ≥70 years and referred for geriatric assessment at two centers in France between 2007 and 2018. The GDS-4's psychometric properties were evaluated against three different measures of depression: the geriatrician's clinical diagnosis (based on a semistructured interview), the 4th edition of the Diagnostic and Statistical Manual of Mental Disorders, and a cluster analysis. The scale's sensitivity, specificity, positive and negative likelihood ratios, and area under the receiver operating characteristic curve (AUROC) were calculated. RESULTS: In a sample of 2,293 patients (median age, 81 years; women, 46%), the GDS-4's sensitivity and specificity for detecting physician-diagnosed depression were, respectively, 90% and 89%. The positive and negative likelihood ratios were 8.2 and 0.11, and the AUROC was 92%. When considering the subset of patients with data on all measures of depression, the sensitivity and specificity values were, respectively, ≥90% and ≥72%, the positive and negative likelihood ratios were, respectively, ≥3.4 and ≤ 0.11, and the AUROC was ≥91%. CONCLUSION: The GDS-4 appears to be a clinically relevant, easy-to-use tool for routine depression screening in older patients with cancer. IMPLICATIONS FOR PRACTICE: Considering the overlap between symptoms of cancer and symptoms of depression, depression is particularly difficult to assess in older geriatric oncology and is associated with poor outcomes; there is a need for a routine psychological screening. Self-report instruments like the 4-item version of the Geriatric Depression Scale appears to be a clinically relevant, easy-to-use tool for routine depression screening in older patients with cancer. Asking four questions might enable physicians to screen older patients with cancer for depression and then guide them toward further clinical evaluation and appropriate care if required.

Effectiveness of pediatric asthma education program in the context of a general hospital in France: A retrospective real-life study.

Objective: To assess the feasibility and effectiveness of a pediatric asthma education program delivered in the context of a French suburban general hospital. Design: Monocentric retrospective study including children with asthma in Melun, Île-de-France, from January to December 2019. Data collected concerned asthma management, symptoms, education, and knowledge. Results: We included 262 patients with a median age of 4.5 years. Asthma education (AE) was taught to 226 (86 %) children, 36 with minimal education (ME), 155 (69 %) with an unstructured asthma education program (USEP) and 71 (31 %) a structured asthma education program (SEP). Patients with an SEP had better knowledge of the disease and its treatment as compared with those with a USEP or ME (p < 0.05). Lung function was evaluated for 70 % of children with ME, 90 % with a USEP (p = 0.144) and 77 % an SEP (p = 0.455). Allergy testing was assessed for 42 % of children with ME, 69 % a USEP (p = 0.020) and 57 % an SEP (p = 0.185). Almost all children with USEP (93 %) and SEP (94 %) also had a written asthma action plan as compared with 49 % of the children with ME (p < 0.001). Also, 76 % of children with ME did not have an asthma follow-up as compared with 37 % with a USEP and 52 % an SEP. Overall, 69 % of children with ME had at least one hospitalization within the year as compared with 32 % with a USEP (p = 0.001) and 59 % an SEP (p = 0.506). Conclusions: An asthma education program delivered in a general hospital resulted in increased disease knowledge for children and their caregivers, together with reduced acute interventions.

Frailty in heart failure according to the presence or absence of wild-type transthyretin cardiac amyloidosis.

AIMS: Wild-type transthyretin cardiac amyloidosis (ATTRwt CA) is a common, underdiagnosed cause of heart failure (HF) in the elderly. Concurrent extracardiac amyloid infiltration might be responsible for a specific frailty phenotype. This study aims to compare the prevalence and characteristics of frailty parameters in HF patients, with or without ATTRwt CA. METHODS: In a comparative cross-sectional study, we prospectively included consecutive HF patients with or without ATTRwt CA (the HF + ATTRwt+ and HF + ATTRwt- groups, respectively) between April 2018 and April 2021. Logistic regression models were used to compare the groups with regard to frailty as assessed using multidimensional geriatric tools. RESULTS: We included 123 patients (68 HF + ATTRwt+ and 55 HF + ATTRwt-). The mean age was 80.9 (standard deviation 6.3) years, 87% were male, 34% had left ventricular systolic dysfunction and 34% were New York Heart Association (NYHA) III. Relative to the HF + ATTRwt- group, patients in the HF + ATTRwt+ group were more likely to have shrinking [odds ratios = 2.9 (95% confidence interval, 1.1 to 1.7), P = 0.03], balance disorders [1.8 (1.1 to 2.8), P = 0.02], memory complaints [2.5, (1.0 to 5.9), P = 0.05] and overactive bladder [1.5 (1.1 to 2.2), P = 0.03], independently of age, sex, NYHA class and diabetes status. The proportion of very frail patients was higher (albeit not significantly) in the HF + ATTRwt+ group than in the HF + ATTRwt- group [2.4 (0.9 to 6.9), P = 0.10]. CONCLUSIONS: ATTRwt CA is associated with a specific frailty phenotype. Patients with ATTRwt CA should be screened for frailty and managed collaboratively by cardiologists and geriatricians, with a view to improving quality of life.

Geriatric assessment and quality of life for 2 years in older patients with head and neck cancer.

Due to the location and toxicity of treatments, head and neck cancer (HNC) has a major impact on quality of life (QoL). Objective: to assess the effects of geriatric-assessment (GA)-driven interventions on QoL over 2 years in older adults with HNC.EGeSOR was a randomized study of HNC patients aged ≥65, receiving a pretreatment GA, a geriatric intervention and follow-up (intervention) or standard of care (control). The primary endpoint was QoL score using the European Organisation for Research and Treatment of Cancer's (EORTC QLQ-C30) and HNC (QLQ-HN35) QoL questionnaires over 24 months.In total, 475 patients were included (median age: 75.3; women: 31%; oral cancer: 44%). QoL scores improved over 24 months with various trajectories, without significant differences between the groups. A total of 74% of patients (interventional group) did not receive the complete intervention. Cancer characteristics, functional status, and risk of frailty were associated with change in the Global Health Status QoL score.There is a need to develop an alternative model of implementation such as patient-centered health-care pathways. TRIAL REGISTRATION: NCT02025062.

Which Occupations Did People Engage in during Lockdown? A European Cross-Sectional Descriptive Survey by Generation.

Objective: The primary objective was to describe the occupations people engaged in more frequently during lockdown than before the coronavirus disease 2019 pandemic as a function of generation. The secondary objectives were to (i) describe the levels of importance, performance, and satisfaction for these occupations and (ii) identify factors affecting the levels of importance, performance, and satisfaction. Method: We conducted an online, cross-sectional survey of young adults (YAs, aged 18-39), middle-aged adults (MAs, aged 40-59), and older adults (OAs, aged 60 or over). Results: 2534 participants (YAs: 47%, MAs: 33%, and OAs: 20%) cited 4500 occupations. The occupations in which people most engaged were leisure occupations (67%), followed by productive occupations (31%) and then self-care (2%) occupations. YAs gave a median (interquartile range) importance score of 8 (6; 9) to leisure, 8 (7; 10) to productivity, and 8 (7; 10) to self-care. MAs gave a median importance score of 8 (6; 10) to leisure, 8 (7; 10) to productivity, and 8 (7; 10) to self-care. OAs gave a median importance score of 8 (7; 10) to leisure, 8 (7; 9) to productivity, and 9 (8; 10) to self-care. In a pre-/postlockdown comparison, the changes in performance scores among YAs were +5 (3; 6) for leisure, +4 (2; 5) for productivity, and +4 (3; 6) for self-care. Among MAs, these changes were, respectively, +4 (3; 6), +3 (2; 5), and +4.5 (3; 6). Among OAs, these changes were, respectively, +3 (1; 5) for leisure, +3 (2; 5) for productivity, and +2 (0; 4) for self-care. The changes in satisfaction scores among YAs were +3 (0; 5) for leisure, +3 (0; 5) for productivity, and +3 (1; 6) for self-care. Among MAs, these changes were, respectively, +3 (0; 5), +2 (0; 4), and +5 (0; 6). Among OAs, these changes were, respectively, +2 (0; 4), +2 (0; 4), and +2 (0; 4). Conclusions: Lockdown led to stronger engagements in quiet leisure and alternative forms of socialization. Occupational therapists may have a role in helping community-dwelling people to balance and structure their new daily routine.

Elevated uranium concentration and low activity ratio (234U/238U) in the Œuf river as the result of groundwater-surface water interaction (Essonne river valley, South of Paris Basin, France).

Uranium (U) is a naturally occurring radioactive heavy metal widely distributed on Earth. Noticeable elevated U concentration and low activity ratio (AR) were occasionally detected in headwater stream of the Essonne river (Seine Basin, France), the namely Œuf river. This paper aims at providing new insight on geogenic U features in headwater streams and examines the role of river-groundwater interaction. The Œuf river was sampled four times in 2020 to investigate the influence of heterogeneous geology and hydrological seasonality. The dissolved fraction of water samples was analyzed for a variety of chemical parameters (anion, major, minor and trace element concentrations, isotopes 234U and 238U). The Œuf river was shown to exhibit elevated U concentration up to 19.3 µg L-1 (exceeding by 100-fold the value of 0.19 µg L-1 known for riverine average) and low AR down to 0.41 (almost the third of the value expected in surface water, i.e., 1.17). The Œuf river got enriched in U when receiving groundwater from Beauce Limestone Aquifer System. High U concentration (above 15 µg L-1) was found in association with low AR (below 0.5) in the stream water when flowing in the outcrop zone of one BLAS unit. Taking advantage of changes in the stream flow conditions and the geochemical contrast between surface and ground waters, mixing volumes were calculated. This study first examined the potential of using U isotopes in combination with selenium as hydrogeochemical tracers of the river-groundwater continuum. In HWS, the aquifer discharge was shown to supply 12 to 59 % of the river water. This study demonstrates the key role played by the river-groundwater interaction on river water chemistry in small streams draining catchment with various geology setting. It also supports the use of combining redox sensitive trace elements to track the river-groundwater continuum.

Determinants of Inclusion in Mainstream School for Children with Autism Spectrum Disorders from the EpiTED Study: A 10-Year Follow-up Cohort.

Inclusion of students with Autism Spectrum Disorder (ASD) in mainstream schools has a positive impact on their social and daily living behaviors. Our objective was to identify clinical and socio-demographic variables promoting or limiting inclusion in mainstream school through childhood and adolescence. The EpiTED study is a long-term, prospective, multicenter cohort of 281 ASD children included before the age of 7, with a 10-year follow-up in France. Variables significantly linked to inclusion in mainstream school were identified using a mixed-effect logistic regression model: greater autonomy [OR = 1.45 (1.29-1.63)], lesser symptom severity [OR = 0.96 (0.92-0.99)] and fewer siblings [OR = 0.86 (0.75-0.99)]. In the multivariate model, the probability for a child of being included in mainstream school decreased over time [OR = 0.91 (0.85-0.97)], i.e. with age.

Systematic review of carbon footprint of surgical procedures.

The ecological sustainability of the operating room (OR) is a matter of recent interest. The present systematic review aimed to review the current literature assessing the carbon footprint of surgical procedures in different surgical fields. Following to the PRISMA statement checklist, three databases (MEDLINE, EMBASE, Cochrane Library) were searched by independent reviewers, who screened records on title and abstract first, and then on the full text. Risk of bias was evaluated using the MINORS system. Over the 878 articles initially identified, 36 original studies were included. They considered ophthalmologic surgical procedures (30.5%), general/digestive surgery (19.4%), gynecologic procedures (13.9%), orthopedic procedures (8.3%), neurosurgery (5.5%), otolaryngology/head and neck surgery (5.5%), plastic/dermatological surgery (5.5%), and cardiac surgery (2.8%). Despite a great methodological heterogeneity, data showed that a single surgical procedure emits 4-814 kgCO2e, with anesthetic gases and energy consumption representing the largest sources of greenhouse gas emission. Minimally invasive surgical techniques may require more resources than conventional open surgery, particularly for packaging and plastics, energy use, and waste production. Each OR has the potential to produce from 0.2 to 4kg of waste per case with substantial differences depending on the type of intervention, hospital setting, and geographic area. Overall, the selected studies were found to be of moderate quality. Based on a qualitative synthesis of the available literature, the OR can be targeted by programs and protocols implemented to reduce the carbon footprint and improve the waste stream of the OR.

Effect of Cholinesterase Inhibitors on Mortality in Patients With Dementia: A Systematic Review of Randomized and Nonrandomized Trials.

BACKGROUND AND OBJECTIVES: Cholinesterase inhibitors (ChEIs) have cardiovascular effects in addition to their neurological activity and might alter mortality. We wanted to know if treatment with ChEIs modifies mortality in patients with dementia. METHODS: We searched PubMed, EMBASE, Cochrane CENTRAL, ClinicalTrials.gov and ICRTP, from their inception to November 2021, and screened bibliographies of reviews, guidelines and included studies. We included randomized controlled trials (RCTs) and non-randomized controlled studies at lower risk of bias comparing ChEI treatment with placebo or usual treatment, for 6 months or longer, in patients with dementia of any type. Two investigators independently assessed studies for inclusion, assessed their risk of bias and extracted data, using predefined forms. Any discordance between investigators was solved by discussion and consensus. Data on all-cause and cardiovascular mortality, measured as either crude death rates or multivariate adjusted hazard ratios (HR), was pooled using a random-effect model. Information size achieved was assessed using trial sequential analysis (TSA). We followed PRISMA guidelines. RESULTS: 24 studies (12 RCTs, 12 cohorts, mean follow-up 6 to 120 months), cumulating 79 153 patients with Alzheimer's (13 studies), Parkinson's (1), vascular (1) or any type (9) dementia, fulfilled inclusion criteria. Pooled all-cause mortality in control patients was 15.1 per 100 person-years. Treatment with ChEIs was associated with lower all-cause mortality (unadjusted RR 0.74, 95%CI 0.66 - 0.84; adjusted HR 0.77, 95%CI 0.70 - 0.84, moderate to high quality evidence). This result was consistent between randomized and non-randomized studies and in several sensitivity analyses. No difference appeared between subgroups by type of dementia, age, individual drug or dementia severity. Less data was available for cardiovascular mortality (3 RCTs, 2 cohorts, 9 182 patients, low to moderate quality evidence), which was also lower in patients treated with ChEIs (unadjusted RR 0.61, 95%CI 0.40 - 0.93, adjusted HR 0.47, 95%CI 0.32 - 0.68). In TSA analysis, results for all-cause mortality were conclusive, but not those for cardiovascular mortality. DISCUSSION: There is moderate to high quality evidence of a consistent association between long-term treatment with ChEIs and a reduction in all-cause mortality in patients with dementia. These findings may influence decisions to prescribe ChEIs in those patients. TRIAL REGISTRATION INFORMATION: This systematic review was registered in the PROSPERO international prospective register of systematic reviews with the number CRD42021254458 (11/06/2021).

Overly broad-spectrum antibiotic treatment of wild-type Pseudomonas aeruginosa infections in relation to the EUCAST new definition of susceptibility testing categories, a retrospective multicentre cohort study.

Objectives: EUCAST changed the definition of the 'intermediate' (I) category in 2019, now defined as 'susceptible, increased exposure'. This new definition could lead to an increased prescription of antibiotics still reported as 'S', compared with those now reported as 'I'. The objective of this study was to evaluate the influence of this definition on the use of overly broad-spectrum antibiotics for the treatment of infections caused by WT Pseudomonas aeruginosa. Methods: A retrospective observational multicentre study was conducted, involving five hospitals. Two 15 month study periods were defined, before and after the implementation of the new definition. All patients with an infection caused by WT P. aeruginosa treated by ß-lactams were included. The main endpoint was the proportion of patients treated by an overly broad-spectrum antibiotic treatment by meropenem or ceftolozane/tazobactam. Results: Two hundred and ninety-one patients were included. No difference between groups was found, in terms of infection, microbiology or demographic characteristics. Two overly broad-spectrum antibiotic treatments by meropenem or ceftolozane/tazobactam were observed in Period 1 (1.2%), versus 13 in Period 2 (10.8%; P < 0.001). No overly broad-spectrum treatment was observed when the antimicrobial stewardship team had given advice. Conclusions: This new definition can cause a negative impact on the use of overly broad-spectrum antibiotic treatment due to misunderstanding by clinicians. Its successful implementation requires adaptation of software for reporting antibiotic susceptibility, a sustained strong information campaign by microbiologists and support by an antimicrobial stewardship team.

Effectiveness of Geriatric Assessment-Driven Interventions on Survival and Functional and Nutritional Status in Older Patients with Head and Neck Cancer: A Randomized Controlled Trial (EGeSOR).

This study assesses the efficacy of Geriatric Assessment (GA)-driven interventions and follow-up on six-month mortality, functional, and nutritional status in older patients with head and neck cancer (HNC). HNC patients aged 65 years or over were included between November 2013 and September 2018 by 15 Ear, Nose, and Throat (ENT) and maxillofacial surgery departments at 13 centers in France. The study was of an open-label, multicenter, randomized, controlled, and parallel-group design, with independent outcome assessments. The patients were randomized 1:1 to benefit from GA-driven interventions and follow-up versus standard of care. The interventions consisted in a pre-therapeutic GA, a standardized geriatric intervention, and follow-up, tailored to the cancer-treatment plan for 24 months. The primary outcome was a composite criterion including six-month mortality, functional impairment (fall in the Activities of Daily Living (ADL) score ≥2), and weight loss ≥10%. Among the patients included (n = 499), 475 were randomized to the experimental (n = 238) or control arm (n = 237). The median age was 75.3 years [70.4-81.9]; 69.5% were men, and the principal tumor site was oral cavity (43.9%). There were no statistically significant differences regarding the primary endpoint (n = 98 events; 41.0% in the experimental arm versus 90 (38.0%); p = 0.53), or for each criterion (i.e., death (31 (13%) versus 27 (11.4%); p = 0.48), weight loss of ≥10% (69 (29%) versus 65 (27.4%); p = 0.73) and fall in ADL score ≥2 (9 (3.8%) versus 13 (5.5%); p = 0.35)). In older patients with HNC, GA-driven interventions and follow-up failed to improve six-month overall survival, functional, and nutritional status.