To evaluate the efficacy of irradiation of internal mammary nodes (IMN) on 10-year overall survival in breast cancer patients after mastectomy.
This multicenter phase 3 study enrolled patients with ...positive axillary nodes (pN+) or central/medial tumors with or without pN+. Other inclusion criteria were age <75 and a Karnofsky index ≥70. All patients received postoperative irradiation of the chest wall and supraclavicular nodes and were randomly assigned to receive IMN irradiation or not. Randomization was stratified by tumor location (medial/central or lateral), axillary lymph node status, and adjuvant therapy (chemotherapy vs no chemotherapy). The prescribed dose of irradiation to the target volumes was 50 Gy or equivalent. The first 5 intercostal spaces were included in the IMN target volume, and two-thirds of the dose (31.5 Gy) was given by electrons. The primary outcome was overall survival at 10 years. Disease-free survival and toxicity were secondary outcomes.
T total of 1334 patients were analyzed after a median follow-up of 11.3 years among the survivors. No benefit of IMN irradiation on the overall survival could be demonstrated: the 10-year overall survival was 59.3% in the IMN-nonirradiated group versus 62.6% in the IMN-irradiated group (P=.8). According to stratification factors, we defined 6 subgroups (medial/central or lateral tumor, pN0 only for medial/central or pN+, and chemotherapy or not). In all these subgroups, IMN irradiation did not significantly improve overall survival.
In patients treated with 2-dimensional techniques, we failed to demonstrate a survival benefit for IMN irradiation. This study cannot rule out a moderate benefit, especially with more modern, conformal techniques applied to a higher risk population.
Fall risk in elderly people is usually assessed using clinical tests. These tests consist in a subjective evaluation of gait performed by healthcare professionals, most of the time shortly after the ...first fall occurrence. We propose to complement this one-time, subjective evaluation, by a more quantitative analysis of the gait pattern using a Microsoft Kinect. To evaluate the potential of the Kinect sensor for such a quantitative gait analysis, we benchmarked its performance against that of a gold-standard motion capture system, namely the OptiTrack. The “Kinect” analysis relied on a home-made algorithm specifically developed for this sensor, whereas the OptiTrack analysis relied on the “built-in” OptiTrack algorithm. We measured different gait parameters as step length, step duration, cadence, and gait speed in twenty-five subjects, and compared the results respectively provided by the Kinect and OptiTrack systems. These comparisons were performed using Bland-Altman plot (95% bias and limits of agreement), percentage error, Spearman’s correlation coefficient, concordance correlation coefficient and intra-class correlation. The agreement between the measurements made with the two motion capture systems was very high, demonstrating that associated with the right algorithm, the Kinect is a very reliable and valuable tool to analyze gait. Importantly, the measured spatio-temporal parameters varied significantly between age groups, step length and gait speed proving the most effective discriminating parameters. Kinect-monitoring and quantitative gait pattern analysis could therefore be routinely used to complete subjective clinical evaluation in order to improve fall risk assessment during rehabilitation.
Increased left ventricular wall thickness (LVWT) is a common finding in cardiology. It is not known how often hereditary transthyretin-related familial amyloid cardiomyopathy (mTTR-FAC) is ...responsible for LVWT. Several therapeutic modalities for mTTR-FAC are currently in clinical trials; thus, it is important to establish the prevalence of TTR mutations (mTTR) and the clinical characteristics of the patients with mTTR-FAC.
In a prospective multicentre, cross-sectional study, the TTR gene was sequenced in 298 consecutive patients diagnosed with increased LVWT in primary cardiology clinics in France. Among the included patients, median (25-75th percentiles) age was 62 50;74; 74% were men; 23% were of African origin; and 36% were in NYHA Class III-IV. Median LVWT was 18 (16-21) mm. Seventeen (5.7%; 95% confidence interval CI: 3.4;9.0) patients had mTTR of whom 15 (5.0%; 95% CI 2.9;8.2) had mTTR-FAC. The most frequent mutations were V142I (n = 8), V50M (n = 2), and I127V (n = 2). All mTTR-FAC patients were older than 63 years with a median age of 74 69;79. Of the 15 patients with mTTR-FAC, 8 were of African descent while 7 were of European descent. In the African descendants, mTTR-FAC median age was 74 72;79 vs. 55 46;65 years in non-mTTR-FAC (P < 0.001). In an adjusted multivariate model, African origin, neuropathy, carpal tunnel syndrome, electrocardiogram (ECG) low voltage, and late gadolinium enhancement (LGE) at cardiac-magnetic resonance imaging were all independently associated with mTTR-FAC.
Five per cent of patients diagnosed with hypertrophic cardiomyopathy have mTTR-FAC. Mutated transthyretin genetic screening is warranted in elderly subjects with increased LVWT, particularly, those of African descent with neuropathy, carpal tunnel syndrome, ECG low voltage, or LGE.
Summary Background Prevention strategies are urgently needed to tackle the growing burden of Alzheimer's disease. We aimed to assess efficacy of long-term use of standardised ginkgo biloba extract ...for the reduction of incidence of Alzheimer's disease in elderly adults with memory complaints. Methods In the randomised, parallel-group, double-blind, placebo-controlled GuidAge clinical trial, we enrolled adults aged 70 years or older who spontaneously reported memory complaints to their primary-care physician in France. We randomly allocated participants in a 1:1 ratio according to a computer-generated sequence to a twice per day dose of 120 mg standardised ginkgo biloba extract (EGb761) or matched placebo. Participants and study investigators and personnel were masked to study group assignment. Participants were followed-up for 5 years by primary-care physicians and in expert memory centres. The primary outcome was conversion to probable Alzheimer's disease in participants who received at least one dose of study drug or placebo, compared by use of the log-rank test. This study is registered with ClinicalTrials.gov , number NCT00276510. Findings Between March, 2002, and November, 2004, we enrolled and randomly allocated 2854 participants, of whom 1406 received at least one dose of ginkgo biloba extract and 1414 received at least one dose of placebo. By 5 years, 61 participants in the ginkgo group had been diagnosed with probable Alzheimer's disease (1·2 cases per 100 person-years) compared with 73 participants in the placebo group (1·4 cases per 100 person-years; hazard ratio HR 0·84, 95% CI 0·60–1·18; p=0·306), but the risk was not proportional over time. Incidence of adverse events was much the same between groups. 76 participants in the ginkgo group died compared with 82 participants in the placebo group (0·94, 0·69–1·28; p=0·68). 65 participants in the ginkgo group had a stroke compared with 60 participants in the placebo group (risk ratio 1·12, 95% CI 0·77–1·63; p=0·57). Incidence of other haemorrhagic or cardiovascular events also did not differ between groups. Interpretation Long-term use of standardised ginkgo biloba extract in this trial did not reduce the risk of progression to Alzheimer's disease compared with placebo. Funding Ipsen.
Because of population ageing, fall prevention represents a human, economic, and social issue. Currently, fall-risk is assessed infrequently, and usually only after the first fall occurrence. Home ...monitoring could improve fall prevention. Our aim was to monitor daily activities at home in order to identify the behavioral parameters that best discriminate high fall risk from low fall risk individuals. Microsoft Kinect sensors were placed in the room of 30 patients temporarily residing in a rehabilitation center. The sensors captured the patients' movements while they were going about their daily activities. Different behavioral parameters, such as speed to sit down, gait speed or total sitting time were extracted and analyzed combining statistical and machine learning algorithms. Our algorithms classified the patients according to their estimated fall risk. The automatic fall risk assessment performed by the algorithms was then benchmarked against fall risk assessments performed by clinicians using the Tinetti test and the Timed Up and Go test. Step length, sit-stand transition and total sitting time were the most discriminant parameters to classify patients according to their fall risk. Coupling step length to the speed required to stand up or the total sitting time gave rise to an error-less classification of the patients, i.e., to the same classification as that of the clinicians. A monitoring system extracting step length and sit-stand transitions at home could complement the clinicians' assessment toolkit and improve fall prevention.
Background
As almost all mental disorders are associated with increased suicidal‐related behavior, anhedonia might be a trans‐diagnostic dimension to target for suicide prevention.
Methods
For this ...3‐year‐long prospective study, 2,839 outpatients with mood disorders were recruited. They were divided in: (a) two groups according to the occurrence or not of suicidal ideation during the follow‐up, and (b) two groups according to the occurrence or not of suicide attempts during the follow‐up. Anhedonia was assessed using a composite score (the French version of the 14‐item Snaith‐Hamilton Pleasure Scale and item 13 of the Quick Inventory of Depressive Symptomatology scale) at inclusion and at 6, 12, 24, and 36 months after inclusion.
Results
Patients with mood disorders and anhedonia at least at one follow‐up visit had a 1.4‐fold higher risk of suicidal ideation (adjusted odds ratio = 1.35; 95% confidence interval 1.07, 1.70), even after adjustment for confounding factors of suicide risk (i.e., bipolar or unipolar disorder, sex, age, marital status, education level, antidepressant intake, personal history of suicide attempt, at least one childhood trauma, and mean of the maximum depression score during the follow‐up). Conversely, association between anhedonia and suicide attempt did not remain significant after adjustment.
Conclusions
The significant association between anhedonia and suicide ideation in patients with mood disorders stresses the need of targeting hedonia in mood disorders, and of research focusing on the position to pleasure in life through eudaimonia.
Background
Acetophenone azine (CAS no. 729‐43‐1) present in sports equipment (shoes, socks and shin pads) has been suspected to induce skin allergies. Twelve case reports of allergy in children and ...adults from Europe and North America were published between 2016 and 2021.
Objectives
The objective of this study was to confirm that acetophenone azine is indeed a skin sensitizer based on in vitro/ in vivo testings derived from the Adverse Outcome Pathway (AOP) built for skin sensitization by OECD in 2012.
Methods
Acetophenone azine was tested in vitro according to the human cell line activation test (h‐CLAT) and the ARE‐Nrf2 Luciferase Test (KeratinoSens) and in vivo using the Local Lymph Nodes Assay (LLNA).
Results
Both the h‐CLAT and the KeratinoSens were positive whereas the LLNA performed at 5, 2.5 and 1% (wt/vol) of acetophenone azine, was negative.
Conclusion
Based on these results, acetophenone azine was considered as a skin sensitizer. This was recently confirmed by its classification under the CLP regulation.
Acetophenone azine (AA) induced skin allergies in humans. Based on in vitro/ in vivo testings derived from the AOP for skin sensitization, AA was positive both in h‑CLAT and KeratinoSens but negative in the LLNA. AA was considered a skin sensitizer. This was recently confirmed by its CLP classification.
Behavioural variant of frontotemporal dementia (bvFTD) is a neurodegenerative disease that is clinically characterised by progressive behavioural changes and social interpersonal dysfunctions. Its ...diagnosis remains a clinical challenge, and depression is one of the main causes of misdiagnoses due to the prevalence of apathy in bvFTD.
To evaluate the sensitivity and specificity of the Social Cognition and Emotional Assessment (SEA) and the mini-SEA for differentiating bvFTD from major depressive disorder (MDD).
Scores for the SEA and mini-SEA for 37 patients with bvFTD (divided into subgroups of 17 with early bvFTD and 20 with moderate bvFTD according to the normal range of the Mattis Dementia Rating Scale), 19 MDD patients and 30 control subjects were compared to define the discrimination power of these tools compared with other standard neuropsychological tests.
SEA and mini-SEA scores were significantly lower for both the early and moderate bvFTD groups compared with control subjects and the MDD group, and very few scores overlapped between patients in the bvFTD subgroups and patients in the MDD and control subgroups. SEA and mini-SEA scores distinguished early bvFTD from MDD with sensitivity and specificity rates above 94%.
Unlike standard executive neuropsychological tests, SEA and the mini-SEA can differentiate MDD from bvFTD in the early stages of the disease. The mini-SEA is an easy tool that can be utilised in neurological or psychiatric departments.
Purpose: Using a dual-task paradigm, 2 experiments (Experiments 1 and 2) were conducted to assess differences in the amount of listening effort expended to understand speech in noise in audiovisual ...(AV) and audio-only (A-only) modalities. Experiment 1 had equivalent noise levels in both modalities, and Experiment 2 equated speech recognition performance levels by increasing the noise in the AV versus A-only modality. Method: Sixty adults were randomly assigned to Experiment 1 or Experiment 2. Participants performed speech and tactile recognition tasks separately (single task) and concurrently (dual task). The speech tasks were performed in both modalities. Accuracy and reaction time data were collected as well as ratings of perceived accuracy and effort. Results: In Experiment 1, the AV modality speech recognition was rated as less effortful, and accuracy scores were higher than A only. In Experiment 2, reaction times were slower, tactile task performance was poorer, and listening effort increased, in the AV versus the A-only modality. Conclusions: At equivalent noise levels, speech recognition performance was enhanced and subjectively less effortful in the AV than A-only modality. At equivalent accuracy levels, the dual-task performance decrements (for both tasks) suggest that the noisier AV modality was more effortful than the A-only modality.
Fall prevention is a human, economic and social issue. The Timed Up and Go (TUG) test is widely used to identify individuals with a high fall risk. However, this test has been criticized because its ..."diagnostic" is too dependent on the conditions in which it is performed and on the healthcare professionals running it. We used the Microsoft Kinect ambient sensor to automate this test in order to reduce the subjectivity of outcome measures and to provide additional information about patient performance. Each phase of the TUG test was automatically identified from the depth images of the Kinect. Our algorithms accurately measured and assessed the elements usually measured by healthcare professionals. Specifically, average TUG test durations provided by our system differed by only 0.001 s from those measured by clinicians. In addition, our system automatically extracted several additional parameters that allowed us to accurately discriminate low and high fall risk individuals. These additional parameters notably related to the gait and turn pattern, the sitting position and the duration of each phase. Coupling our algorithms to the Kinect ambient sensor can therefore reliably be used to automate the TUG test and perform a more objective, robust and detailed assessment of fall risk.
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