Association between Risk of Obstructive Sleep Apnea and Cognitive Performance, Frailty, and Quality of Life Among Older Adults with Atrial Fibrillation

Background: Geriatric impairments and obstructive sleep apnea (OSA) are prevalent among patients with atrial fibrillation (AF) and adversely impact patient’s long-term outcomes. Little is known, however, about the association between OSA and frailty, cognitive performance, and AF-related quality of life in older men and women with AF. Objective: To examine the association of OSA with frailty, cognitive performance, and AF- related quality of life among older adults with AF. Methods: Data from the Systemic Assessment of Geriatrics Elements-AF study were used which includes participants ≥ 65 years with AF and a CHA2DS2-VASc ≥ 2. Multivariable adjusted logistic regression models were used to examine the association between OSA, as measured by the STOP-BANG questionnaire, and geriatric impairments including frailty, cognitive performance, and AF-related quality of life. Results: A total of 970 participants with AF (mean age 75 years, 51% male) were included in the analysis. Among the 680 participants without a medical history of OSA, 179 (26%) participants had low risk of OSA, 360 (53%) had an intermediate risk, and 141 participants (21%) had a high risk for OSA. Compared to those with low risk of OSA, those at intermediate or high risk for OSA were significantly more likely to be frail (aOR= 1.66, 95% CI: 1.08–2.56; aOR= 3.00, 95% CI: 1.69-5.32, respectively) after adjusting for sociodemographic, clinical, and health behavioral variables. Risk of OSA was not associated with cognitive performance and AF- related quality of life after adjusting for several potentially confounding factors. Conclusions: Older adults with AF who are at intermediate or high risk for OSA have a greater likelihood of being frail. Our findings identify a group of patients at high risk who would benefit from early screening for OSA. Future longitudinal studies are needed to assess the effect of OSA treatment on frailty, physical functioning, and QoL among patients with AF

Paratubal serous borderline tumor in an 85 years old woman: A case report

Paratubal cysts are incidental, common and benign lesions with few cases of borderline tumor and adenocarcinoma been reported in the literature. Herein, we are discussing a case of an 85 years old woman who visited her Obstetrics and Gynecologist for a chief complaint of post-menopausal bleeding. Physical examination revealed a slightly enlarged uterus. The diagnosis of fibroids were made on ultrasound. A total hysterectomy with bilateral salpingo-oophorectomy was performed without complications. The gross examination of the specimen was most remarkable for multiple intramural fibroids and a right simple paratubal cyst meausirng 1 × 1 cm. Microscopical evaluation of the paratubal cyst showed a simple cyst lined by stratified cuboidal epithelium with mild cytologic atypia and no stromal invasion, findings consistent with serous borderline tumor rising in a paratubal cyst. Due to the small size of the tumor and its confinement to the cyst, a follow-up was advised. Serous borderline tumors arising in paratubal cyst are very rare with only eight cases reported in the literature. Their existence should be acknowledged to plan patient treatment and outcome

Digital health tools to promote diabetes education and management of cardiovascular risk factors among under-resourced populations

Diabetes is a major risk factor for the development of cardiovascular disease, the leading cause of death in the United States, further highlighting the need for improved diabetes management, particularly among individuals from ethnic minorities or low socioeconomic status

Technology, community, and equity: Considerations for collecting social determinants data

Gathering detailed information on an individual’s neighborhood environment is becoming increasingly recognized as a crucial component of understanding the impact that social determinants have on individual and public health, and this has been further highlighted by the ongoing COVID-19 pandemic. Emerging research clearly demonstrates COVID-19’s differential impact on underserved and rural communities, and it is imperative to adequately capture important neighborhood-level predictors of health outcomes to better understand the extent to which these communities have been affected, and to equitably promote their recovery and healing. mHealth tools have drastically transformed the framework of data collection within clinical and population health research and can significantly reduce accessibility barriers for research participants to allow for convenient, continuous real-time health and activity space assessments. Digital interventions leveraging remote data collection, and providing study participants with requisite devices when necessary, serves to bridge the digital divide that would otherwise preclude rural populations’ participation in key research opportunities for advancing health equity

Identification de gènes impliqués dans des dysplasies osseuses rares dans des familles libanaises consanguines

La pratique du mariage entre apparentés au sein de la population libanaise, favorisée par des raisons sociales, religieuses, géographiques et aussi politiques, a vu apparaître des sous-groupes de populations de taille plus ou moins réduite, parfois à la limite d isolats génétiques. Ceci a engendré une augmentation de la prévalence des maladies autosomiques récessives fréquentes mais aussi et surtout rares. Parmi ces dernières, les chondrodysplasies ont retenu notre attention. Elles sont caractérisées par un retard statural dû à un défaut du processus d ossification endochondale, qui est responsable de la croissance des os longs. Au cours de ces dernières décennies, plus de 230 gènes responsables d environ 400 maladies osseuses constitutionnelles ont été identifiés. Cependant, les bases moléculaires d'une centaine de dysplasies osseuses restent, à ce jour, inconnues. L identification de gènes codant pour des protéines de nature extrêmement variée a contribué à la compréhension du mécanisme complexe d ossification endochondrale. Mon travail de thèse, réalisé en cotutelle entre l équipe de recherche Bases moléculaires et physiopathologiques des chondrodysplasies de l hôpital Necker enfants-malades, à Paris en France et l Unité de Génétique Médicale (UGM) de l Université Saint-Joseph au Liban, a consisté à identifier des gènes impliqués dans des dysplasies osseuses autosomiques récessives dans quatre familles libanaises consanguines. Dans ce cadre, différentes stratégies ont été adoptées. La première a été une stratégie d intersection des variations détectées par le séquençage de l exome de deux patients, atteints d une forme sévère de dysplasie spondylodysplastique létale et issus de deux familles libanaises consanguines et non apparentées (Familles A et B). Nous avons identifié une mutation homozygote du gène MAGMAS (NM_016069, p.Asn76Asp) (Mitochondria-associated granulocyte macrophage CSF-signaling molecule) à l origine de la maladie dans les deux familles A et B. MAGMAS est une protéine associée à la mitochondrie et impliquée dans la régulation de l import actif des protéines vers la matrice mitochondriale. Par immunohistochimie, nous avons montré que MAGMAS est spécifiquement exprimée au niveau de l os et de la zone hypertrophique du cartilage. MAGMAS, ayant une fonction cruciale pour la survie, est très conservé entre les espèces. Après avoir généré des souches de levures exprimant une copie normale ou mutée du gène humain MAGMAS, nous avons validé l effet délétère de la mutation p.Asn76Asp, i) sur la croissance des levures, en montrant que les souches portant le gène humain muté présentent un caractère thermosensible, ii) sur la fonction d import des protéines vers la matrice mitochondriale, qui est altérée dans les souches mutées et iii) sur la stabilité de la protéine. Nous avons également observé un effet de la mutation sur la morphologie des mitochondries et des peroxysomes des cellules de levures, suggérant une induction de l autophagie dans les souches de levures portant la mutation p.Asn76Asp. L identification de mutations de MAGMAS dans une dysplasie osseuse sévère, permet d attribuer à cette protéine un rôle spécifique dans le processus complexe d ossification endochondrale. La deuxième stratégie a été une combinaison, au sein d une même famille, d une stratégie de cartographie par homozygotie et du séquençage de l exome d un seul patient. Cette approche a été utilisée dans une famille consanguine avec 3 enfants atteints porteurs d une dysplasie rhizomélique (Famille C). Nous avons identifié une mutation homozygote du gène NWD1 (NACHT and WD repeat domain containing 1) (NM_001007525, p.Cys1376Tyr) responsable de la maladie dans cette famille C. Ce gène code pour une protéine ayant des domaines WD répétés qui lui confèrent un rôle dans divers mécanismes comme la transduction de signal, la régulation de la transcription, le transport vésiculaire et le contrôle du cycle cellulaire. (...)Social, religious, geographic and political reasons have favored the consanguineous marriage in the Lebanese population. This led to an increase in the prevalence of autosomal recessive disorders, especially the rare entities including chondrodysplasias. This group of diseases is due to an impairment of the endochondral ossification process. Causative mutations have now been identified in over 230 different genes in more than 400 unique skeletal phenotypes. However, the genetic basis of over 100 different entities remains to be determined. My PhD research project, held between the research group Bases moléculaires et physiopathologiques des chondrodysplasies of Necker enfants-malades hospital (INSERM U781, PARIS, France) and the Medical Genetics Unit of Saint-Joseph University (Lebanon), aims to identify genes involved in autosomal recessive skeletal dysplasias in four consanguineous Lebanese families. Different strategies were carried out: the first consists in overlapping data from whole exome sequencing of two patients affected by a new lethal type of spondylodysplastic dysplasia and issued from two consanguineous unrelated Lebanese families (Families A and B). Here, we report a homozygous missense mutation in the Mitochondria-associated granulocyte macrophage CSF-signaling gene (MAGMAS: NM_016069, p.Asn76Asp) in this severe skeletal dysplasia. MAGMAS, also referred to as PAM16, is a mitochondria-associated protein, involved in pre-proteins import into mitochondria and essential for cell growth and development. We demonstrate that MAGMAS is expressed in trabecular bone and cartilage at early developmental stages underlining its specific role in skeletogenesis. We also give strong evidence of the deleterious effect of the identified mutation on the stability of the protein, its in-vivo activity and the viability of yeast strains. We also show that the mutation is able to induce autophagy in yeast cells. Reporting deleterious MAGMAS mutation in a skeletal dysplasia supports a key and specific role for this mitochondrial protein in ossification. Additional studies would be of interest to further understand the specific role of magmas in ossification. The second strategy was to combine, in a consanguineous family, homozygosity mapping with whole exome sequencing of one of the patients. This strategy was undertaken in family C with 3 patients affected by a rhizomelic dysplasia. It allowed us to identify a homozygous missense mutation in the NWD1 gene (NACHT and WD repeat domain containing 1: NM_001007525, p.Cys1376Tyr) as responsible for the skeletal dysplasia in this family. NWD1 belongs to a large group of WD-repeat domain-containing proteins that are involved in different physiological mechanisms such as signal transduction, transcription regulation, vesicular transport and cell cycle control. (...)PARIS5-Bibliotheque electronique (751069902) / SudocSudocFranceF

Prognostic value of geriatric conditions for death and bleeding in older patients with atrial fibrillation

Background: Geriatric conditions, such as frailty and cognitive impairment, are prevalent in older patients with atrial fibrillation (AF). We examined the prognostic value of geriatric conditions for predicting 1-year mortality and bleeding events in these patients. Methods: SAGE (Systematic Assessment of Geriatric Elements)-AF study is a multicenter cohort study which enrolled individuals (mean age 75 years, 48% women, 86% taking oral anticoagulation) 65 years and older with AF and CHA2DS2 -VASc score of 2 or higher from clinics in Massachusetts and Georgia, USA between 2016 and 2018. A six-component geriatric assessment included validated measures of frailty, cognitive function, social support, depressive symptoms, vision, and hearing was performed at baseline. Study endpoints included all-cause mortality and clinically relevant bleeding. Results: At 1 year, 1,097 (96.5%) individuals attended the follow up visit, 44 (3.9%) had died, and 56 (5.1%) had clinically relevant bleeding. After adjustment for demographic and clinical factors, social isolation (odds ratio [OR] 1.69, 95% confidence interval [CI]: 1.01-2.84), depression (OR 1.94, 95% CI: 1.28-2.95) and frailty (OR 2.55, 95% CI: 1.55-4.19) were significantly associated with the composite endpoint of death or clinically relevant bleeding. After multivariable adjustment, depression (OR 1.79, 95% CI 1.09-2.93) and frailty (OR 2.83, 95% CI 1.55-5.17) were significantly associated with clinically relevant bleeding. Conclusions: Social isolation, depression, and frailty were prognostic of dying or experiencing clinically relevant bleeding during the coming year in older men and women with AF. Assessing geriatric impairments merits consideration in the care of these patients

Clinically Meaningful Change in Quality of Life and Associated Factors Among Older Patients With Atrial Fibrillation

Background: Among older patients with atrial fibrillation, there are limited data examining clinically meaningful changes in quality of life (QoL). We examined the extent of, and factors associated with, clinically meaningful change in QoL over 1-year among older adults with atrial fibrillation. Methods and Results: Patients from cardiology, electrophysiology, and primary care clinics in Massachusetts and Georgia were enrolled in a cohort study (2015-2018). The Atrial Fibrillation Effect on Quality-of-Life questionnaire was used to assess overall QoL and across 3 subscales: symptoms, daily activities, and treatment concern. Clinically meaningful change in QoL (ie, difference between 1-year and baseline QoL score) was categorized as either a decline ( \u3c /=-5.0 points), no clinically meaningful change (-5.0 to +5.0 points), or an increase ( \u3e /=+5.0 points). Ordinal logistic models were used to examine factors associated with QoL changes. Participants (n=1097) were on average 75 years old, 48% were women, and 87% White. Approximately 40% experienced a clinically meaningful increase in QoL and 1 in every 5 patients experienced a decline in QoL. After multivariable adjustment, women, non-Whites, those who reported depressive and anxiety symptoms, fair/poor self-rated health, low social support, heart failure, or diabetes mellitus experienced clinically meaningful declines in QoL. Conclusions: These findings provide insights to the magnitude of, and factors associated with, clinically meaningful change in QoL among older patients with atrial fibrillation. Assessment of comorbidities and psychosocial factors may help identify patients at high risk for declining QoL and those who require additional surveillance to maximize important clinical and patient-centered outcomes

“Fork and bracket” syndrome expands the spectrum of SBF1-related sensory motor polyneuropathies

Charcot-Marie-Tooth neuropathy type 4 (CMT4) comprises a large group of genetically heterogeneous progressive sensory motor neuropathies characterized by autosomal recessive inheritance. Among these, CMT4B includes 3 forms related to genes of the myotubularin family, namely CMT4B1 (MTMR2), CMT4B2 (MTMR13/SBF2), and CMT4B3 (MTMR5/SBF1)

Multimorbidity, physical frailty, and self-rated health in older patients with atrial fibrillation

BACKGROUND: Holistic care models emphasize management of comorbid conditions to improve patient-reported outcomes in treatment of atrial fibrillation (AF). We investigated relations between multimorbidity, physical frailty, and self-rated health (SRH) among older adults with AF. METHODS: Patients (n = 1235) with AF aged 65 years and older were recruited from five medical centers in Massachusetts and Georgia between 2015 and 2018. Ten previously diagnosed cardiometabolic and 8 non-cardiometabolic conditions were assessed from medical records. Physical Frailty was assessed with the Cardiovascular Health Study frailty scale. SRH was categorized as either excellent/very good , good , and fair/poor . Separate multivariable ordinal logistic models were used to examine the associations between multimorbidity and SRH, physical frailty and SRH, and multimorbidity and physical frailty. RESULTS: Overall, 16% of participants rated their health as fair/poor and 14% were frail. Hypertension (90%), dyslipidemia (80%), and heart failure (37%) were the most prevalent cardiometabolic conditions. Arthritis (51%), anemia (31%), and cancer (30%), the most common non-cardiometabolic diseases. After multivariable adjustment, patients with higher multimorbidity were more likely to report poorer health status (Odds Ratio (OR): 2.15 [95% CI: 1.53-3.03], \u3e /= 8 vs 1-4; OR: 1.37 [95% CI: 1.02-1.83], 5-7 vs 1-4), as did those with more prevalent cardiometabolic and non-cardiometabolic conditions. Patients who were pre-frail (OR: 1.73 [95% CI: 1.30-2.30]) or frail (OR: 6.81 [95% CI: 4.34-10.68]) reported poorer health status. Higher multimorbidity was associated with worse frailty status. CONCLUSIONS: Multimorbidity and physical frailty were common and related to SRH. Our findings suggest that holistic management approaches may influence SRH among older patients with AF