Effectiveness and safety of belantamab mafodotin in patients with relapsed or refractory multiple myeloma in real-world setting: The ALFA study.

OBJECTIVES: The aim of this noninterventional, retrospective ALFA study was to describe belantamab mafodotin effectiveness and safety in patients with relapsed/refractory multiple myeloma in a real-world setting in France. METHODS: Response rate, progression-free survival (PFS), overall survival (OS), and safety were assessed. RESULTS: Among the 184 patients initiating belantamab mafodotin treatment, the overall response rate was 32.7% (≥very good partial response [VGPR] 20.4%, partial response [PR] 12.3%). The median PFS (mPFS) was 2.4 months (95% confidence interval [CI]: 1.9, 3.3), and median OS (mOS) was 8.8 months (95% CI: 6.3, 11.6). According to best response, mPFS was 20.6 months (95% CI: 12.1, not reached [NR]) in patients with ≥VGPR and 7.1 months (95% CI: 4.6, 9.4) in patients with PR; mOS was NR in patients with ≥VGPR and 17.5 months (95% CI: 7.7, NR) in patients with PR. For both OS and PFS, no differences were found in subgroups of interest. The adverse events (AEs) reported in 159 patients (86.4%) were mostly ocular AEs. CONCLUSIONS: ALFA, the largest real-world cohort conducted so far, confirms the results of belantamab mafodotin as reported in the DREAMM-2 clinical trial. The clinical benefit is significant as long as the patient is a responder.

Construction and Validation of an Individual Deprivation Index: a Study Based on a Representative Cohort of the Paris Metropolitan Area.

The association between health status and deprivation is well established. However, it is difficult to measure deprivation at an individual level and already-existing indices in France are not validated or do not meet the needs of health practitioners. The aim of this work was to establish a validated, easy-to-use, multidimensional, relevant index that was representative of the population in the Paris metropolitan area. From the SIRS 2010 cohort study, 14 socio-economic characteristics were selected: health insurance, educational background, socio-professional category, professional status, feelings of loneliness, emotional situation, household type, income, perceived financial situation, social support (support in daily life, financial and emotional), housing situation, and migration origin. In addition, a total of 12 health status, healthcare use, and nutrition-related variables were also selected. Content validity and internal validity of the index were explored. The 14 socio-economic indicators were associated to varying degrees with poorer health status, less use of healthcare, and poorer nutrition and were distributed across the 14 multiple-choice questions of the index. Each answer was rated from 0 to 2. The index value of 10 that isolates 20% of the most deprived individuals was used as threshold. "Being deprived," as defined with this value, was significantly associated with 9 of the 12 studied health variables. This index could be a relevant instrument in the assessment of deprivation and social inequalities of health.

The Bidirectional Relationship between Vision and Cognition: A Systematic Review and Meta-analysis.

TOPIC: Visual impairment (VI) and cognitive impairment (CIM) are prevalent age-related conditions that impose substantial burden on the society. Findings on the hypothesized bidirectional association of VI and CIM remains equivocal. Hence, we conducted a systematic review and meta-analysis to examine this bidirectional relationship. CLINICAL RELEVANCE: Sixty percent risk of CIM has not been well elucidated in the literature. A bidirectional relationship between VI and CIM may support the development of strategies for early detection and management of risk factors for both conditions in older people. METHODS: PubMed, Embase, and Cochrane Central registers were searched systematically for observational studies, published from inception until April 6, 2020, in adults 40 years of age or older reporting objectively measured VI and CIM assessment using clinically validated cognitive screening tests or diagnostic evaluation. Meta-analyses on cross-sectional and longitudinal associations between VI and CIM outcomes (any CIM assessed using screening tests and clinically diagnosed dementia) were examined. Random effect models were used to generate pooled odds ratios (ORs) and 95% confidence intervals (CIs). We also examined study quality, publication bias, and heterogeneity. RESULTS: Forty studies were included (n = 47 913 570). Meta-analyses confirmed that persons with VI were more likely to have CIM, with significantly higher odds of: (1) any CIM (cross-sectional: OR, 2.38 [95% CI, 1.84-3.07]; longitudinal: OR, 1.66 [95% CI, 1.46-1.89]) and (2) clinically diagnosed dementia (cross-sectional: OR, 2.43 [95% CI, 1.48-4.01]; longitudinal: OR, 2.09 [95% CI, 1.37-3.21]) compared with persons without VI. Significant heterogeneity was explained partially by differences in age, sex, and follow-up duration. Also, some evidence suggested that individuals with CIM, relative to cognitively intact persons, were more likely to have VI, with most articles (8/9 [89%]) reporting significantly positive associations; however, meta-analyses on this association could not be conducted because of insufficient data. DISCUSSION: Overall, our work suggests that VI is a risk factor of CIM, although further work is needed to confirm the association of CIM as a risk factor for VI. Strategies for early detection and management of both conditions in older people may minimize individual clinical and public health consequences.

Vision loss and 12-year risk of dementia in older adults: the 3C cohort study.

To analyze the longitudinal relationships between vision loss and the risk of dementia in the first 2 years, from 2 to 4 years and beyond 4 years after inclusion and to determine the roles of depressive symptomatology and engagement in cognitively stimulating activities in these associations. This study is based on the Three-City (3C) study, a population-based cohort of 7736 initially dementia-free participants aged 65 years and over with 12 years of follow-up. Near visual impairment (VI) was measured and distance visual function (VF) loss was self-reported. Dementia was diagnosed and screened over the 12-year period. At baseline, 8.7% had mild near VI, 4.2% had moderate to severe near VI, and 5.3% had distance VF loss. Among the 882 dementia cases diagnosed over the 12-year follow-up period, 140 cases occurred in the first 2 years, 149 from 2 to 4 years and 593 beyond 4 years after inclusion. In Cox multivariate analysis, moderate to severe near VI was associated with an increased risk of dementia in the first 2 years (HR 2.0, 95% CI 1.2-3.3) and from 2 to 4 years (HR 1.8, 95% CI 1.1-3.1) but the association was not significant beyond 4 years after inclusion even if pointing in similar direction (HR 1.3, 95% CI 0.95-1.9). Mild near VI was associated with an increased risk of dementia only in the first 2 years (HR 1.6, 95% CI 1.1-2.5). Moreover, self-reported distance VF loss was associated with an increased risk beyond 4 years after inclusion (HR 1.5, 95% CI 1.1-2.0) but the association was no longer significant after taking into account baseline cognitive performances. Further adjustment for engagement in cognitively stimulating activities only slightly decreased these associations. However, there was an interaction between vision loss and depressive symptomatology, with vision loss associated with dementia only among participants with depressive symptomatology. These results suggest that poor vision, in particular near vision loss, may represent an indicator of dementia risk at short and middle-term, mostly in depressed elderly people.

Visual Loss and Subsequent Activity Limitations in the Elderly: The French Three-City Cohort.

OBJECTIVES: To investigate the relationship between vision and disability in the elderly. METHODS: We used a baseline visual indicator (combining near acuity with Snellen equivalent < 20/30 and self-reported distance visual loss) to explore the association between visual loss and subsequent disability (mobility, instrumental activities of daily living [IADLs], ADLs, and participation restriction) from 1999 to 2007 in 8491 elderly participants of the French Three-City Cohort (Bordeaux, Dijon, and Montpellier). RESULTS: In multiadjusted analyses, near visual impairment, alone or associated with distance visual function loss, was associated with greater risk of developing ADL limitations (P = .027), IADL limitations (P = .002), and participation restriction (P < .001), but not mobility (P = .848). The disabling impact of visual loss was significant for 11 of the 15 activities, when analyzed one by one. CONCLUSIONS: Both near and distance visual loss was associated with greater functional decline over time, and the combination of the two could be even worse. Public Health Implications. In the context of rapid aging of the population, maintaining good vision in the elderly represents a promising prevention track, visual impairment being common in the elderly, largely undermanaged, and mostly reversible. Further research, especially trials, is necessary to estimate the public health impact of such interventions.

Use of interferon gamma release assays in clinical practice: review of QuantiFERON-TB prescription in a French university hospital.

BACKGROUND: In recent years, the clinical use of interferon gamma release assays (IGRAs) has increased exponentially, while their indications remain controversial given difficulties in interpretation. Four indications were recommended by the French National Authority for Health (HAS) in 2006. We evaluated the utilization of the QuantiFERON-TB Gold In-Tube (QFT-IT) test over a 1-y period in a French university hospital and the impact of IGRA results in particular. METHODS: The QFT-IT tests requested in 2009 were analysed retrospectively, excluding those from the Occupational Health Department, the Regional Tuberculosis Centre, and rheumatology consultations for which the indications were clearly defined. RESULTS: Three hundred and sixty QFT-IT tests were analysed. The interpretation was frequently problematic given the inclusion of a significant proportion of patients over 80 y of age (11%), immunocompromised patients (43%), and patients with a known history of tuberculosis (6%). The indications failed to comply with HAS recommendations in 42% of cases (151/360), i.e. 14% of all QFT-IT tests in 2009. Thirty-seven percent of request forms were related to suspected pulmonary tuberculosis. In the case of a positive QFT-IT test, the clinical decision-making was changed in 58% of cases when the indications met the HAS recommendations, compared with only 16% if they did not (p < 0.005). CONCLUSION: When the indications do not meet the health authority recommendations, the diagnostic value of the IGRA remains limited.

Association Between Vision and Brain Cortical Thickness in a Community-Dwelling Elderly Cohort.

Purpose: Visual impairment is a major cause of disability and impairment of cognitive function in older people. Brain structural changes associated with visual function impairment are not well understood. The objective of this study was to assess the association between visual function and cortical thickness in older adults. Methods: Participants were selected from the French population-based ESPRIT cohort of 2259 community-dwelling adults ≥65 years old enrolled between 1999 and 2001. We considered visual function and brain MRI images at the 12-year follow-up in participants who were right-handed and free of dementia and/or stroke, randomly selected from the whole cohort. High-resolution structural T1-weighted brain scans acquired with a 3-Tesla scanner. Regional reconstruction and segmentation involved using the FreeSurfer image-analysis suite. Results: A total of 215 participants were included (mean [SD] age 81.8 [3.7] years; 53.0% women): 30 (14.0%) had central vision loss and 185 (86.0%) normal central vision. Vision loss was associated with thinner cortical thickness in the right insula (within the lateral sulcus of the brain) as compared with the control group (mean thickness 2.38 [0.04] vs 2.50 [0.03] mm, 4.8% thinning, pcorrected= 0.04) after adjustment for age, sex, lifetime depression and cardiovascular disease. Conclusion: The present study describes a significant thinning of the right insular cortex in older adults with vision loss. The insula subserves a wide variety of functions in humans ranging from sensory and affective processing to high-level cognitive processing. Reduced insula thickness associated with vision loss may increase cognitive burden in the ageing brain.

Prevalence and Associated Factors of Uncorrected Refractive Error in Older Adults in a Population-Based Study in France.

Importance: Uncorrected refractive error (URE) is a common cause of visual impairment, but its prevalence in groups of older adults who could be pragmatic targets for improving optical correction remains unknown. Objectives: To estimate the prevalence of URE in older adults, particularly in those with age-related eye disease and those who are unable to attend an outpatient clinic, and to identify the factors associated with URE. Design, Setting, and Participants: This population-based cross-sectional analysis included 707 adults 78 years or older from the Alienor Study in Bordeaux, France. Data were collected from February 12, 2011, through December 21, 2012, and analyzed from November 1, 2017, through July 7, 2018. Main Outcomes and Measures: Uncorrected refractive error was defined as the presenting distance visual acuity in the better-seeing eye improved by at least 5 letters on the Early Treatment Diabetic Retinopathy Study chart (≥1 line on the logMAR chart) using the best-achieved optical correction. Multivariate logistic regressions were used to determine the factors associated with URE. Results: The study population of 707 adults 78 years or older (64.8% women; mean [SD] age, 84.3 [4.4] years) had a prevalence of URE of 38.8% (95% CI, 35.2%-42.5%). Prevalence was high for participants with eye disease (range, 35.0% [95% CI, 28.4%-42.0%] to 44.1% [95% CI, 27.2%-62.1%], depending on the disease) and those without eye disease (30.1%; 95% CI, 24.0%-36.7%). Prevalence was higher in participants who were examined at home (because they could not come to the clinic) than in those examined at the clinic (49.4% [95% CI, 42.8%-55.9%] vs 33.5% [95% CI, 29.2%-37.9%]; P < .001). Having an eye examination performed at home (odds ratio [OR], 1.64; 95% CI, 1.13-2.37), living alone (OR, 0.65; 95% CI, 0.47-0.90), and having the perceptions that the ophthalmologist consultation fees are too expensive (OR, 1.94; 95% CI, 1.12-3.36) and that declining visual acuity is normal with aging (OR, 1.47; 95% CI, 1.04-2.08) were all associated with URE. Conclusions and Relevance: These study results show that the prevalence of URE was high in this population and suggest that preventive strategies aimed at enhancing optical correction could be directed to all older adults and to specific groups by implementing at-home eye examinations for those who have difficulties attending an outpatient clinic and by focusing on those with eye disease who probably already have a regular ophthalmologic follow-up. More studies are needed to evaluate prevalence of URE in different populations and countries with various eye care systems.

Visual Impairment, Undercorrected Refractive Errors, and Activity Limitations in Older Adults: Findings From the Three-City Alienor Study.

Purpose: As vision is required in almost all activities of daily living, visual impairment (VI) may be one of the major treatable factors for preventing activity limitations. We aimed to evaluate the attributable risk of VI associated with activity limitations and the extent to which limitations are avoidable with optimal optical correction of undercorrected refractive errors. Methods: We analyzed 709 older adults from the Three-City-Alienor population-based study. VI was defined by presenting distance visual acuity in the better-seeing eye. Multivariate modified Poisson regressions were used to estimate the associations between vision, activity limitations, and social participation restrictions. Population attributable risk (PAR) and generalized impact fraction (GIF) were estimated. Bootstrapping was used to estimate 95% confidence intervals (CI). Results: After adjustment for potential confounders, VI was associated with each domain of activity limitations, except basic activities of daily living (ADL) limitations. These associations were found for even minimal levels of VI. PAR was estimated at 10.1% (95% CI: 5.2-10.6) for mobility limitations, at 26.0% (95% CI: 13.5-41.2) for instrumental ADL (IADL) limitations, and at 24.9% (95% CI: 10.5-47.1) for social participation restrictions. GIF for improvement of undercorrected refractive errors was 6.1% (95% CI: 3.8-8.5) for mobility limitations, 15.8% (95% CI: 11.5-20.1) for IADL limitations and 21.4% (95% CI: 13.8-28.5) for social participation restrictions. Conclusions: About one-sixth of IADL limitations and one-fifth of social participation restrictions could be prevented by an optimal optical correction. These results underline the importance of eye examinations in older adults to prevent disability.

The effect of introducing IGRA to screen French healthcare workers for tuberculosis and potential conclusions for the work organisation.

INTRODUCTION: In France, pre-employment screening for tuberculosis (TB) is performed for healthcare workers (HCW). Screening is repeated when exposure to TB patients or infectious material occurs. The results of these TB screenings were analysed in a retrospective analysis. METHOD: Tuberculin skin tests (TST) and interferon-gamma release assays (QuantiFERON® Gold In-Tube - QFT) were used to perform the TB screenings. The screening results of 637 HCWs on whom QFT was performed were taken from the records of the University Hospital of Nantes. RESULTS: In three (0.5%) HCW, the QFT was indeterminate. In 22.2%, the QFT was positive. A second QFT was performed in 118 HCWs. The reversion rate was 42% (5 out of 17). The conversion rate was 6% (6 out of 98). A TST was performed on 466 (73.5%) of the HCWs. Results for TST > 10 mm were 77.4%. In those with a TST < 10 mm, QFT was positive in 14% and in those with a TST ≥ 10 mm, QFT was positive in 26.7%. Depending on the definition for conversion in the QFT, the annual attack rate was 4.1% or 7.3%. X-ray and pneumology consultation was based on positive QFT rather than TST alone (52 out of 56). No active TB was detected. CONCLUSION: The TST overestimated the prevalence of LTBI in this cohort. The decision about X-ray and consultation regarding preventive treatment should be based on the QFT rather than the TST results. The high reversion rate should be taken into consideration when consulting with HCWs regarding preventive treatment. The high conversion rate seems to indicate that preventive measures such as wearing masks should be improved.

Evaluation of the tuberculin skin test and the interferon-gamma release assay for TB screening in French healthcare workers.

INTRODUCTION: Using French cut-offs for the Tuberculin Skin Test (TST), results of the TST were compared with the results of an Interferon-gamma Release Assay (IGRA) in Healthcare Workers (HCW) after contact to AFB-positive TB patients. METHODS: Between May 2006 and May 2007, a total of 148 HCWs of the University Hospital in Nantes, France were tested simultaneously with IGRA und TST. A TST was considered to indicate recent latent TB infection (LTBI) if an increase of >10 mm or if TST >/= 15 mm for those with no previous TST result was observed. For those with a positive TST, chest X-ray was performed and preventive chemotherapy was offered. RESULTS: All HCWs were BCG-vaccinated. The IGRA was positive in 18.9% and TST >/= 10 mm was observed in 65.5%. A recent LTBI was believed to be highly probable in 30.4% following TST. Agreement between IGRA and TST was low (kappa 0.041). In 10 (16.7%) out of 60 HCWs who needed chest X-ray following TST the IGRA was positive. In 9 (20%) out of 45 HCWs to whom preventive chemotherapy was offered following TST the IGRA was positive. Of those considered TST-negative following the French guidelines, 20.5% were IGRA-positive. In a two-step strategy - positive TST verified by IGRA - 18 out of 28 (64.3%) IGRA-positive HCWs would not have been detected using French guidelines for TST interpretation. CONCLUSION: The introduction of IGRA in contact tracings of BCG-vaccinated HCWs reduces X-rays and preventive chemotherapies. Increasing the cut-off for a positive TST does not seem to be helpful to overcome the effect of BCG vaccination on TST.