Iterative qualitative approach to establishing content validation of a patient-reported outcome measure for arm lymphedema:the LYMPH-Q Upper Extremity Module

Background: Breast cancer-related lymphedema (BRCL) is one of the most common causes of upper extremity (UE) lymphedema in developed nations and substantially impacts health-related quality of life. To advance our understanding of the epidemiology and treatment of BRCL, rigorously developed and validated patient-reported outcome measures (PROMs) are needed. This study aimed to demonstrate the iterative content validity of a modular UE lymphedema-specific PROM called the LYMPH-Q UE module. Methods:A multi-step iterative qualitative approach was used. Semi-structured interview data from in-depth qualitative interviews with adult women (18 years and older) with BCRL were used to develop the first set of the LYMPH-Q UE scales. The content validity of these scales was demonstrated with patient and clinician feedback. Over the course of cognitive debriefing interviews, additional concepts of lymphedema worry and impact on work were identified as missing from the LYMPH-Q UE module. Subsequently, two new qualitative studies (a focus group and in-depth concept elicitation interviews with patients) were conducted, and two new scales were developed to measure lymphedema worry and impact on work life and their content validity was dResults: emonstrated. Qualitative data from in-depth and cognitive interviews with 15 (age 40–74 years) and 16 (age 38–74 years) women with BRCL, respectively, and feedback from 12 clinical experts, were used to develop and demonstrate the content validity of six LYMPH-Q UE scales measuring symptoms, function, appearance, psychological, information, and arm sleeve. Additionally, data from in-depth interviews with 12 (age 35–72 years) women with UE lymphedema and four focus groups (n = 16 women; age 35–74 years) was used to develop and assess the content validity of two new LYMPH-Q UE scales measuring lymphedema worry and impact on work life. The content validity of the previously established six scales was also demonstrated in these subsequent qualitative studies. Conclusion: The LYMPH-Q UE is a modular PROM developed using international guidelines for PROM development and can be used in clinical practice, research, and quality improvement to enhance patient-centered shared decision-making. This study’s innovative and iterative approach to content validation demonstrates that the LYMPH-Q UE is a comprehensive measure that includes important concepts relevant to patients with UE lymphedema.</p

MRI Surveillance and Breast Cancer Mortality in Women With <i>BRCA1</i> and <i>BRCA2</i> Sequence Variations

Importance: Magnetic resonance imaging (MRI) surveillance is offered to women with a pathogenic variant in the BRCA1 or BRCA2 gene who face a high lifetime risk of breast cancer. Surveillance with MRI is effective in downstaging breast cancers, but the association of MRI surveillance with mortality risk has not been well defined. Objective: To compare breast cancer mortality rates in women with a BRCA1 or BRCA2 sequence variation who entered an MRI surveillance program with those who did not. Design, Setting, and Participants: Women with a BRCA1 or BRCA2 sequence variation were identified from 59 participating centers in 11 countries. Participants completed a baseline questionnaire between 1995 and 2015 and a follow-up questionnaire every 2 years to document screening histories, incident cancers, and vital status. Women who had breast cancer, a screening MRI examination, or bilateral mastectomy prior to enrollment were excluded. Participants were followed up from age 30 years (or the date of the baseline questionnaire, whichever was later) until age 75 years, the last follow-up, or death from breast cancer. Data were analyzed from January 1 to July 31, 2023. Exposures: Entrance into an MRI surveillance program. Main Outcomes and Measures: Cox proportional hazards modeling was used to estimate the hazard ratios (HRs) and 95% CIs for breast cancer mortality associated with MRI surveillance compared with no MRI surveillance using a time-dependent analysis. Results: A total of 2488 women (mean [range] age at study entry 41.2 [30-69] years), with a sequence variation in the BRCA1 (n = 2004) or BRCA2 (n = 484) genes were included in the analysis. Of these participants, 1756 (70.6%) had at least 1 screening MRI examination and 732 women (29.4%) did not. After a mean follow-up of 9.2 years, 344 women (13.8%) developed breast cancer and 35 women (1.4%) died of breast cancer. The age-adjusted HRs for breast cancer mortality associated with entering an MRI surveillance program were 0.20 (95% CI, 0.10-0.43; P  Conclusion and Relevance: Results of this cohort study suggest that among women with a BRCA1 sequence variation, MRI surveillance was associated with a significant reduction in breast cancer mortality compared with no MRI surveillance. Further studies of women with BRCA2 sequence variations are needed to ascertain these women obtain the same benefits associated with MRI surveillance.</p

Selecting a BRCA risk assessment model for use in a familial cancer clinic

<p>Abstract</p> <p>Background</p> <p>Risk models are used to calculate the likelihood of carrying a <it>BRCA1 </it>or <it>BRCA2 </it>mutation. We evaluated the performances of currently-used risk models among patients from a large familial program using the criteria of high sensitivity, simple data collection and entry and <it>BRCA </it>score reporting.</p> <p>Methods</p> <p>Risk calculations were performed by applying the BRCAPRO, Manchester, Penn II, Myriad II, FHAT, IBIS and BOADICEA models to 200 non-<it>BRCA </it>carriers and 100 <it>BRCA </it>carriers, consecutively tested between August 1995 and March 2006. Areas under the receiver operating characteristic curves (AUCs) were determined and sensitivity and specificity were calculated at the conventional testing thresholds. In addition, subset analyses were performed for low and high risk probands.</p> <p>Results</p> <p>The BRCAPRO, Penn II, Myriad II, FHAT and BOADICEA models all have similar AUCs of approximately 0.75 for <it>BRCA </it>status. The Manchester and IBIS models have lower AUCs (0. and 0.47 respectively). At the conventional testing thresholds, the sensitivities and specificities for a <it>BRCA </it>mutation were, respectively, as follows: BRCAPRO (0.75, 0.62), Manchester (0.58,0.71), Penn II (0.93,0.31), Myriad II (0.71,0.63), FHAT (0.70,0.63), IBIS (0.20,0.74), BOADICEA (0.70, 0.65).</p> <p>Conclusion</p> <p>The Penn II model most closely met the criteria we established and this supports the use of this model for identifying individuals appropriate for genetic testing at our facility. These data are applicable to other familial clinics provided that variations in sample populations are taken into consideration.</p

Étude des caractéristiques du style d'apprentissage des écoliers en difficulté d'apprentissage au primaire

Cette étude vise une meilleure connaissance des caractéristiques des écoliers en difficulté d'apprentissage au primaire. Pour ce faire, le style d'apprentissage a été retenu comme objet d'étude parce qu'il se situe dans un contexte d'adaptation de l'enseignement aux caractéristiques des écoliers afin de prévenir et de corriger les difficultés d'apprentissage. L'analyse de différents modèles relatifs au style d'apprentissage a permis de choisir un modèle qui prend en considération plusieurs aspects de l'apprenant. Ainsi, le modèle de Lamontagne (1983a, 1983b, 1984), inspiré de l'approche développée aux Etats-Unis par le Dr. Hill (1974) et expérimentée au "Oakland Community College", a été retenu. Dans l'esprit de cet auteur, l'apprentissage est essentiellement une recherche de sens et le style réfère à la façon privilégiée par l'apprenant pour donner du sens à son environnement. Le style d'apprentissage se compose des préférences de l'individu en regard du décodage et du traitement de l'information ainsi que de l'environnement social pour apprendre. Lamontagne a adapté cette approche au contexte québécois et développé des instruments de mesure du style d'apprentissage pour les différents niveaux du système scolaire. Le relevé de la littérature a montré qu'il n'existe pas, actuellement, de données sur les caractéristiques du style d'apprentissage des écoliers québécois en difficulté d'apprentissage du niveau primaire. De plus, les résultats des études américaines sur le sujet sont parfois contradictoires pour des raisons qui tiennent à la fois de leur orientation théorique et de leur méthodologie. L'objectif général de la présente étude est de connaître le style d'apprentissage des écoliers en difficulté du primaire et, plus spécifiquement d'identifier leurs particularités. Les quatre hypothèses de recherche ont été formulées de façon à vérifier si les écoliers en difficulté utilisent plus que les écoliers sans difficulté le mode de communication oral, l'encadrement par l'adulte, le mode d'induction catégoriel et la démarche déductive. Pour procéder à la vérification des hypothèses, toute la population étudiante de la deuxième à la sixième année d'une commission scolaire a été retenue. Ainsi, mille deux cents écoliers sans difficulté d'apprentissage et cent trente-six écoliers en difficulté ont participé à la recherche. Ces derniers étaient ceux qui fréquentaient une classe régulière tout en bénéficiant des services de rééducation. Le questionnaire LAM-I-EL-C (Lamontagne, 1987) a été administré à tous les sujets par les titulaires de classes. Les résultats ont montré que les écoliers en difficulté d'apprentissage présentent des caractéristiques particulières en fonction des cycles du primaire et de certains aspects du style d'apprentissage. Ainsi, ces particularités du style d'apprentissage sont, au 1"*" cycle, l'encadrement par les pairs et le mode d'induction catégoriel et, au 2" cycle, l'encadrement par l'adulte et la démarche déductive. En conséquence, la recherche sur le sujet devrait être poursuivie car le style d'apprentissage est une voie prometteuse pour l'adaptation de l'enseignement aux caractéristiques des écoliers dans une perspective de prévention et de correction des difficultés d'apprentissage

Selecting a BRCA risk assessment model for use in a familial cancer clinic

Abstract Background Risk models are used to calculate the likelihood of carrying a BRCA1 or BRCA2 mutation. We evaluated the performances of currently-used risk models among patients from a large familial program using the criteria of high sensitivity, simple data collection and entry and BRCA score reporting. Methods Risk calculations were performed by applying the BRCAPRO, Manchester, Penn II, Myriad II, FHAT, IBIS and BOADICEA models to 200 non-BRCA carriers and 100 BRCA carriers, consecutively tested between August 1995 and March 2006. Areas under the receiver operating characteristic curves (AUCs) were determined and sensitivity and specificity were calculated at the conventional testing thresholds. In addition, subset analyses were performed for low and high risk probands. Results The BRCAPRO, Penn II, Myriad II, FHAT and BOADICEA models all have similar AUCs of approximately 0.75 for BRCA status. The Manchester and IBIS models have lower AUCs (0. and 0.47 respectively). At the conventional testing thresholds, the sensitivities and specificities for a BRCA mutation were, respectively, as follows: BRCAPRO (0.75, 0.62), Manchester (0.58,0.71), Penn II (0.93,0.31), Myriad II (0.71,0.63), FHAT (0.70,0.63), IBIS (0.20,0.74), BOADICEA (0.70, 0.65). Conclusion The Penn II model most closely met the criteria we established and this supports the use of this model for identifying individuals appropriate for genetic testing at our facility. These data are applicable to other familial clinics provided that variations in sample populations are taken into consideration

Adjuvant Chemotherapy for Breast Cancer in a Patient with Primary Autoimmune Neutropenia

We report an extremely rare and complex case of a 44-year-old woman diagnosed with an early stage triple negative breast cancer in the setting of primary autoimmune neutropenia with a pre-existing severe neutropenia. This case-report demonstrates that adjuvant chemotherapy for breast cancer can be administered in a patient with severe neutropenia. The management is however complicated and requires careful monitoring of side-effects related to both chemotherapy and treatment of autoimmune neutropenia. The role of chemotherapy in the treatment of triple negative breast cancer, the approach to autoimmune neutropenia and potential interactions are reviewed. To our knowledge, this is the first case reporting on the use of chemotherapy in a patient with severe pre-existing primary autoimmune neutropenia

Synergic Interactions Between Hepatic Stellate Cells and Uveal Melanoma in Metastatic Growth

Uveal melanoma (UM) is a malignant intraocular tumor that spreads to the liver in half of the cases. Since hepatic cells could play a role in the therapeutic resistance of metastatic UM, the purpose of our study was to investigate the pro-invasive role of hepatic stellate cells (HSteCs) in metastatic UM at the micro- and macro-metastatic stages. We first performed an immunostaining with the alpha-smooth muscle actin (&alpha;SMA) to localize activated HSteCs in UM liver macro-metastases from four patients. Their accumulation of collagen was assessed with Masson&rsquo;s Trichrome stain. Next, we inoculated metastatic UM cells alone or with human HSteCs in triple-immunodeficient mice, in order to determine if HSteCs are recruited as early as the micro-metastatic stage. The growth of metastatic foci was imaged in the liver by ex vivo fluorescence imaging. Histological analyses were performed with Masson&rsquo;s Trichrome and Picrosirius Red stains, and antibodies against Melan-A and &alpha;SMA. The collagen content was measured in xenografts by quantitative polarization microscopy. In patient hepatectomy samples, activated HSteCs and their pathological matrix were localized surrounding the malignant lesions. In the mouse xenograft model, the number of hepatic metastases was increased when human HSteCs were co-inoculated. Histological analyses revealed a significant recruitment of HSteCs near the micro/macrolesions, and an increase in fibrillar collagen production. Our results show that HSteCs can provide a permissive microenvironment and might increase the therapeutic resistance of metastatic UM