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1.
Artigo em Inglês | MEDLINE | ID: mdl-39368732

RESUMO

OBJECTIVE: There is a high burden of reintervention after repair of Tetralogy of Fallot (TOF). We compare procedural burden and late outcomes in valve sparing repair (VSR) and transannular patch (TAP) cohorts over 30 years. METHODS: Patients undergoing TOF repair (1990-2021, excluding complex TOF) were included in this study (n=1239) with subsequent comparisons between TAP (n=550) and VSR (n=648) cohorts. Descriptive statistics, cumulative incidence frequencies, survival analysis and propensity matching (n=425) were used to analyze reintervention burden and survival. RESULTS: Overall survival of the cohort was 96.7% at 15 years and 95.6% at 25 years, with similar survival between TAP and VSR cohorts (p=0.22). TAP cohort had increased incidence of procedural burden at 25 years (TAP 69.8% versus VSR 37.2%, p<0.001), with 34.6% undergoing ≥2 reinterventions. TAP cohort had higher incidence of surgical PV replacement at 15 years (TAP 20.7% versus VSR 7.6%, p<0.001) and placement of PA stents (TAP 20.2% versus VSR 4.9%, p<0.001). By contrast, VSR had higher incidence of RVOT reoperation at 15 years (VSR 7.3% versus TAP 3.6%, p=0.047). After propensity matching there was no survival advantage between the VSR and TAP cohorts (Era 2) whereas the need for RVOT reoperation was not different between the two cohorts (p=0.060). CONCLUSIONS: The procedural burden remains high following TOF repair. TAP is associated with higher procedural burden in matched and non-matched cohorts. VSR has increased risk of reoperation for RVOT obstruction only in non-matched comparisons. Anatomical complexity and surgical repair strategy influence procedural burden following TOF repair.

2.
J Health Popul Nutr ; 43(1): 156, 2024 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-39363212

RESUMO

BACKGROUND: Primary health care professionals are held accountable for various quality measures in the treatment of patients with chronic diseases such as diabetes. Uncontrolled type 2 diabetes (T2D) remains a considerable health problem; thus, further studying patients with this condition is important for delivering effective interventions. Social determinants of health (SDoH) have been shown to affect various aspects of diabetes care in different subpopulations. We studied the association of SDoH with uncontrolled T2D in a population of adult primary care patients. METHODS: We retrospectively searched our electronic health record for adult patients (≥18 years) with a diagnosis of T2D and a hemoglobin A1c (HbA1c) level of 8% or higher. Patients were empaneled to 2 primary care clinic sites between January 1, 2021, and January 31, 2022. Patients were grouped by HbA1c level to stratify patients according to the extent of uncontrolled T2D. Patient characteristics were compared among groups. Unadjusted and adjusted multinomial logistic regression analysis was used to estimate the odds of various SDoH factors among patient groups with different levels of uncontrolled T2D. RESULTS: The study cohort included 1,596 patients. Most patients were White (79%), and the median age was 58.8 years. The median HbA1c level was 8.9%, and approximately 68% of patients were obese (body mass index [BMI] ≥30). When the study population was grouped by HbA1c level (8% to < 9% [n = 806], ≥9% to < 12% [n = 684], and ≥12% [n = 106]), significant differences among groups were observed in age group (P < .001), marital status (P < .001), race (P < .001), ethnicity (P = .001), and BMI category (P = .01). In groups with higher HbA1c levels, we noticed a higher percentage of patients who were aged 51 to 65 years or single. Among patients with uncontrolled HbA1c levels, more patients were obese than overweight. Patients in the intermediate HbA1c group had increased odds of food insecurity and some decreased social connections, even after adjusting for age, sex, race, ethnicity, and marital status. CONCLUSIONS: Among patients with uncontrolled T2D, higher HbA1c levels were associated with decreased social connections and increased food insecurity. Our findings provide insight into the role of these SDoH in managing T2D and have important implications for primary care practice.


Assuntos
Diabetes Mellitus Tipo 2 , Hemoglobinas Glicadas , Determinantes Sociais da Saúde , Humanos , Diabetes Mellitus Tipo 2/terapia , Pessoa de Meia-Idade , Masculino , Feminino , Estudos Retrospectivos , Idoso , Hemoglobinas Glicadas/análise , Adulto , Determinantes Sociais da Saúde/estatística & dados numéricos , Segurança Alimentar/estatística & dados numéricos , Atenção Primária à Saúde/estatística & dados numéricos
3.
medRxiv ; 2024 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-39371142

RESUMO

Emerging evidence has shown that assortative mating (AM) is a key factor that shapes the landscape of complex human traits. It can increase the overall prevalence of disorders, influence occurrences of comorbidities, and bias estimation of genetic architectures. However, there is lack of large-scale studies to examine the cultural differences and the generational trends of AM for psychiatric disorders. Here, using national registry datasets, we conduct the largest scale of AM analyses on nine psychiatric disorders, with up to 1.4 million mated cases and 6 million matched controls. We performed meta-analyses on AM estimates from Taiwan, Denmark, and Sweden, to examine the potential impact of cultural differences. Generational changes for people born after 1930s were investigated as well. We found that AM of psychiatric disorders are consistent across nations and persistent over generations, with a small proportion of disorders showing generational changes of AM. Our results provide additional insight into the mechanisms of AM across psychiatric disorders and have evident implications on the estimation of the genetic architectures of psychiatric disorders.

4.
ACS Appl Mater Interfaces ; 16(39): 51807-51815, 2024 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-39291561

RESUMO

Two-photon polymerization (TPP) as an unparalleled technology empowers the rapid prototyping of customized three-dimensional (3D) micro/nanostructures, garnering noticeable interest in tissue engineering, drug delivery, and regenerative medicine. These applications have a high requirement on the biocompatibility and integrity of 3D structures. Therefore, it is important to develop two-photon initiator with good water-solubility, initiation efficiency, and biocompatibility. Here, we share our insights into the development of a water-soluble two-photon initiator (WTPI) and applications from the material and manufacturing perspective. We highlight the nonlinear optical properties and the synthesis of WTPI through three pathways. Then we further demonstrate the applications of the TPP technique in the aqueous phase in the fields of tissue engineering, 4D printing, and ceramic manufacturing. Finally, a general conclusion and outlook are provided for the future development and application of WTPI.

5.
Commun Med (Lond) ; 4(1): 180, 2024 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-39300237

RESUMO

BACKGROUND: It has been proposed that having a psychiatric disorder could increase the risk of developing a gastrointestinal disorder, and vice versa. The role of familial coaggregation and shared genetic loading between psychiatric and gastrointestinal disorders remains unclear. METHODS: This study used the Taiwan National Health Insurance Research Database; 4,504,612 individuals born 1970-1999 with parental information, 51,664 same-sex twins, and 3,322,959 persons with full-sibling(s) were enrolled. Genotyping was available for 106,796 unrelated participants from the Taiwan Biobank. A logistic regression model was used to examine the associations of individual history, affected relatives, and polygenic risk scores (PRS) for schizophrenia (SCZ), bipolar disorder (BPD), major depressive disorder (MDD), and obsessive-compulsive disorder (OCD), with the risk of peptic ulcer disease (PUD), gastroesophageal reflux disease (GERD), irritable bowel syndrome (IBS), and inflammatory bowel disease (IBD), and vice versa. RESULTS: Here we show that parental psychiatric disorders are associated with gastrointestinal disorders. Full-siblings of psychiatric cases have an increased risk of gastrointestinal disorders except for SCZ/BPD and IBD; the magnitude of coaggregation is higher in same-sex twins than in full-siblings. The results of bidirectional analyses mostly remain unchanged. PRS for SCZ, MDD, and OCD are associated with IBS, PUD/GERD/IBS/IBD, and PUD/GERD/IBS, respectively. PRS for PUD, GERD, IBS, and IBD are associated with MDD, BPD/MDD, SCZ/BPD/MDD, and BPD, respectively. CONCLUSIONS: There is familial coaggregation and shared genetic etiology between psychiatric and gastrointestinal comorbidity. Individuals with psychiatric disorder-affected relatives or with higher genetic risk for psychiatric disorders should be monitored for gastrointestinal disorders, and vice versa.


It has been proposed that people with psychiatric disorders such as depression could have an increased chance of developing gastrointestinal disorders such as irritable bowel syndrome. We looked at whether this was the case in a large number of people from Taiwan. We found that people with a psychiatric disorder, or with relatives having a psychiatric disorder, were more likely to have gastrointestinal disorders, and vice versa. These findings suggest that people who have psychiatric disorders or have psychiatric disorder-affected relatives should be monitored for gastrointestinal disorders, and vice versa, to enable them to benefit from all the treatments they might need to improve their health.

6.
Artigo em Inglês | MEDLINE | ID: mdl-39321870

RESUMO

BACKGROUND: Long-term enlargement of the aortic arch after aortic arch reconstruction (AAR) in hypoplastic left heart syndrome (HLHS) is not well described. METHODS: Aortic arch measurements for 50 patients with HLHS who achieved Fontan completion were converted to Pediatric Heart Network z-scores. Dimensions were assessed using linear mixed models and differences among time points were evaluated with F-tests. Sub-analysis was conducted comparing Norwood (n=36) vs hybrid (n=14) strategies. RESULTS: Median time to last imaging was 6.4 (IQR, 3.5-11.3) years. Prior to intervention, the main pulmonary artery was dilated whereas the ascending aorta (AA), transverse arch (TA), and isthmus (ISTH) were hypoplastic. With AAR, there were expected increases in all arch z-scores. The aortic arch continued to dilate after AAR reaching peak values at 7 months [Neo-Aortic Complex (NAC): z= 6.9 (5.6-8.0)] or 12 months following stage I [AAo: z=6.1 (2.9-8.3); TA: z=4.7 (3.0-5.9)]. Following peak values, there was a gradual decline in z-scores with most components still at least mildly dilated at 16 years [NAC: z=3.2 (3.1-3.9), AAo: z=3.9 (3.3-4.2); TA: z=3.1 (2.5-3.7)] with abrupt calibre change at ISTH: z= -0.8 (-1.1- -0.3)]. Norwood and hybrid strategies showed similar enlargement profiles after 7 months of age. CONCLUSIONS: Neo-aortic root and aortic arch in HLHS are enlarged early after AAR and continue to enlarge out of proportion to normal controls until 12 months of age, with gradual decline in enlargement up to adolescence. Further work should focus on modifiable surgical factors which may prove important to optimize arch growth and geometry.

7.
BMC Geriatr ; 24(1): 646, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39090539

RESUMO

This study investigated the moderating effect of financial strain or social support on depressive symptoms among older people living alone in Taiwan. Data were collected from the "Taiwan Longitudinal Study on Aging (TLSA)," which included 1513 participants aged 65 and over, among them, 153 (10.1%) were living alone, while 1360 (89.9%) were living with others. Measurement tools included the Depression scale (CES-D), financial stress scale, social support scale, ADL scale, IADL scale, and stress scale, with Cronbach's α coefficients were 0.85, 0.78, 0.67, 0.91, 0.90, and 0.70 respectively. Hierarchical multiple regression was used to examine the moderator effect. The findings revealed that (1) Financial strain was found to moderate the relationship between living alone and depressive symptoms, acting as a promotive moderator among older men living alone. For older women, financial stress does not moderate the relationship between living alone and depressive symptoms. However, financial strain was also identified as a significant factor associated with depressive symptoms among older women living alone. (2) Social support does not moderate effect on the relationship between living alone and depressive symptoms in older men or older women. These results underscore the importance of considering financial stress in mental health policy development by government agencies. It is imperative to address the unique challenges faced by older individuals living alone, particularly in relation to financial strain, in order to promote their mental well-being.


Assuntos
Depressão , Estresse Financeiro , Apoio Social , Humanos , Masculino , Idoso , Feminino , Depressão/psicologia , Depressão/epidemiologia , Depressão/economia , Estudos Longitudinais , Idoso de 80 Anos ou mais , Estresse Financeiro/psicologia , Estresse Financeiro/epidemiologia , Taiwan/epidemiologia
8.
Stem Cells ; 2024 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-39097775

RESUMO

It has been documented that caspase 3 activity is necessary for skeletal muscle regeneration, but how its activity is regulated is largely unknown. Our previous report shows that intracellular TMEM16A, a calcium activated chloride channel, significantly regulates caspase 3 activity in myoblasts during skeletal muscle development. By using a mouse line with satellite cell (SC)-specific deletion of TMEM16A, we examined the role of TMEM16A in regulating caspase 3 activity in SC (or SC-derived myoblast) as well as skeletal muscle regeneration. The mutant animals displayed apparently impaired regeneration capacity in adult muscle along with enhanced ER stress and elevated caspase 3 activity in Tmem16a-/- SC derived myoblasts. Blockade of either excessive ER stress or caspase 3 activity by small molecules significantly restored the inhibited myogenic differentiation of Tmem16a-/- SCs, indicating that excessive caspase 3 activity resulted from TMEM16A deletion contributes to the impaired muscle regeneration and the upstream regulator of caspase 3 was ER stress. Our results revealed an essential role of TMEM16A in satellite cell mediated skeletal muscle regeneration by ensuring a moderate level of caspase 3 activity.

9.
Zhonghua Nan Ke Xue ; 30(6): 547-563, 2024 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-39212365

RESUMO

OBJECTIVE: To evaluate the efficacy and safety of traditional Chinese medicine (TCM) in the treatment of male immune infertility (MII) by meta-analysis. METHODS: We retrieved randomized controlled trial (RCT) on the treatment of male immune infertility with traditional Chinese medicine from the databases of WanFang, Chinese Biomedical Literature, Cochrane Library, Weipu, PubMed and CNKI, and performed methodological quality assessment of the RCTs identified and statistical analysis and evaluation of the publication bias using the RevMan5.4 software. RESULTS: Totally, 25 RCTs (2 563 cases) were included in this study. Compared with Western medicine alone in the treatment of MII, TCM achieved a significantly higher total effectiveness rate (OR = 6.35, 95% CI: 4.96-8.13, P<0.000 01), negative conversion rate of seminal plasma anti-sperm antibodies (OR = 4.52, 95% CI: 2.72 - 7.51, P<0.000 01), negative rate of serum anti-sperm antibodies (OR = 2.98, 95% CI: 2.23-3.96, P<0.000 01), sperm concentration (MD = 15.56, 95% CI: 11.32-19.79, P<0.000 01), grade a sperm motility (MD = 3.85, 95% CI: 1.91-5.79, P=0.000 01), grade a+b sperm motility (MD = 13.77, 95% CI: 7.06-20.48, P<0.000 1), sperm viability (MD = 10.32, 95% CI: 6.78-13.86, P<0.000 01) and pregnancy rate (OR = 3.53, 95% CI: 2.68-4.63, P<0.000 01), but a lower rate of adverse reactions (OR = 0.06, 95% CI: 0.01-0.23, P<0.000 01). There was no statistically significant difference in the percentage of morphologically abnormal sperm between TCM and Western medicine alone in the treatment of MII (MD = -7.53, 95% CI: -15.50-0.44, P = 0.06). CONCLUSION: TCM has a definite effectiveness and high safe in the treatment of male immune infertility.


Assuntos
Medicamentos de Ervas Chinesas , Infertilidade Masculina , Humanos , Masculino , Medicamentos de Ervas Chinesas/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Medicina Tradicional Chinesa/métodos , Fitoterapia
10.
Int J Ophthalmol ; 17(8): 1462-1468, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39156778

RESUMO

AIM: To analyze the distribution of fibrovascular proliferative membranes (FVPMs) in proliferative diabetic retinopathy (PDR) patients that treated with pars plana vitrectomy (PPV), and to evaluate the outcomes separately. METHODS: This was a retrospective and cross-sectional study. Consecutive 25-gauge (25-G) PPV cases operated for PDR from May 2018 to April 2020. According to the FVPMs images outlined after operations, subjects were assigned into three groups: arcade type group, juxtapapillary type group, and central type group. All patients were followed up for over one year. General characteristics, operation-related variables, postoperative parameters and complications were recorded. RESULTS: Among 103 eyes recruited, the FVPMs distribution of nasotemporal and inferiosuperioral was significantly different (both P<0.01), with 95 (92.23%) FVPMs located in the nasal quadrants, and 74 (71.84%) in the inferior. The eyes with a central FVPM required the longest operation time, with silicon oil used in most patients, generally combined with tractional retinal detachment (RD) and rhegmatogenous RD, the worst postoperative best-corrected visual acuity (BCVA) and the highest rates of recurrent RD (all P<0.05). FVPM type, age of onset diabetes mellitus, preoperative BCVA, and combined with tractional RD and rhegmatogenous RD were significantly associated with BCVA improvement (all P<0.05). Compared with the central type group, the arcade type group had higher rates of BCVA improvement. CONCLUSION: FVPMs are more commonly found in the nasal and inferior mid-peripheral retina in addition to the area of arcade vessels. Performing 25-G PPV for treating PDR eyes with central FVPM have relatively worse prognosis.

11.
Transplantation ; 108(9): 1922-1930, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-39167562

RESUMO

BACKGROUND: Ex vivo heart perfusion (EVHP) of donation after circulatory death (DCD) hearts has become an effective strategy in adults; however, the small circulating volume in pediatrics poses the challenge of a low-hemoglobin (Hb) perfusate. We aimed to determine the impact of perfusate Hb levels during EVHP on DCD hearts using a juvenile porcine model. METHODS: Sixteen DCD piglet hearts (11-14 kg) were reperfused for 4 h in unloaded mode followed by working mode. Metabolism, cardiac function, and cell damage were compared between the low-Hb (Hb, 5.0-5.9 g/dL; n = 8) and control (Hb, 7.5-8.4 g/dL; n = 8) groups. Between-group differences were evaluated using 2-sample t -tests or Fisher's Exact tests. RESULTS: During unloaded mode, the low-Hb group showed lower myocardial oxygen consumption ( P < 0.001), a higher arterial lactate level ( P = 0.001), and worse systolic ventricular function ( P < 0.001). During working mode, the low-Hb group had a lower cardiac output (mean, 71% versus 106% of normal cardiac output, P = 0.010) and a higher arterial lactate level ( P = 0.031). Adjusted cardiac troponin-I ( P = 0.112) did not differ between the groups. Morphological myocyte injury in the left ventricle was more severe in the low-Hb group ( P = 0.028). CONCLUSIONS: Low-Hb perfusate with inadequate oxygen delivery induced anaerobic metabolism, resulting in suboptimal DCD heart recovery and declined cardiac function. Arranging an optimal perfusate is crucial to organ protection, and further endeavors to refine the priming volume of EVHP or the transfusion strategy are required.


Assuntos
Transplante de Coração , Hemoglobinas , Perfusão , Animais , Hemoglobinas/metabolismo , Hemoglobinas/análise , Perfusão/métodos , Suínos , Consumo de Oxigênio , Miocárdio/metabolismo , Miocárdio/patologia , Modelos Animais , Sus scrofa , Preservação de Órgãos/métodos
12.
BMC Ophthalmol ; 24(1): 329, 2024 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-39112923

RESUMO

BACKGROUND: Considering that changes in the choroidal thickness are closely related to ocular growth, we studied the choroidal thickness (CT) and the blood flow features in children with unilateral myopic anisometropia (UMA) as well as investigating the relationship between choroidal changes and myopia. METHODS: Subjective refractive, axial length (AL), and biometric parameters were measured in 98 UMA children (age: 8-15 years). CT and choroidal blood-flow features, including the choroidal vessel volume (CVV), choroidal vascularity index (CVI), and choriocapillaris perfusion area (CCPA), were measured through swept-source optical coherence tomography angiography. The macular region was categorized into four concentric circles of diameters 0-1 mm (central fovea), 1-3 mm (parafovea), 3-6 mm (perifovea), and 6-9 mm (extended), and further categorized into superior (S), inferior (I), temporal (T), and nasal (N) quadrants. RESULTS: The aforementioned four regions of myopic eyes displayed significantly lower CT, CVV, and CVI than those of non-myopic eyes. CCPA changes differed across different regions of both the eyes (parts of N and T quadrants). There was an inverse association between CT and the interocular AL difference (central and other regions S, T quadrant). No correlation was noted between CVV and CVI with interocular AL difference. CT and CVV were positively correlated in the 0-6-mm macular region of myopic eyes (Spearman correlation coefficient = 0.763, P < 0.001). CONCLUSIONS: In UMA children, CCT and blood flow may be related to myopia progression. A robust correlation between CT and CVV in the 0-6-mm macular region and reduced CT and diminished blood flow indicated an association with myopia.


Assuntos
Anisometropia , Comprimento Axial do Olho , Corioide , Miopia , Fluxo Sanguíneo Regional , Tomografia de Coerência Óptica , Humanos , Corioide/irrigação sanguínea , Corioide/patologia , Corioide/diagnóstico por imagem , Criança , Adolescente , Masculino , Feminino , Anisometropia/fisiopatologia , Miopia/fisiopatologia , Tomografia de Coerência Óptica/métodos , Comprimento Axial do Olho/patologia , Fluxo Sanguíneo Regional/fisiologia , Refração Ocular/fisiologia , Angiofluoresceinografia/métodos
13.
J Perinatol ; 44(10): 1485-1490, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39147790

RESUMO

OBJECTIVE: Blood product transfusion is a common practice in infants with hypoxic-ischemic encephalopathy (HIE) undoing therapeutic hypothermia (TH). The advantages and disadvantages of conservative or liberal transfusion practices in this fragile population are unknown. Study aims to characterize the transfusion practices in infants with HIE and investigate the association with outcome. STUDY DESIGN: We conducted a retrospective cohort study at a single level IV NICU, evaluating transfusion thresholds, as well as the association between hematological abnormalities or blood product transfusions and outcomes in infants admitted with HIE. RESULT: By univariate analysis, FFP transfusion was associated with increased in-hospital death. However, multivariate analysis adjusting for HIE severity demonstrated no association between hematological abnormality or blood product transfusion and death, nor with neurodevelopmental impairment. CONCLUSION: No association was found between hematological blood product transfusion and death or neurodevelopmental impairment in a retrospective single NICU study of infants with HIE.


Assuntos
Hipóxia-Isquemia Encefálica , Humanos , Hipóxia-Isquemia Encefálica/terapia , Estudos Retrospectivos , Recém-Nascido , Masculino , Feminino , Unidades de Terapia Intensiva Neonatal , Mortalidade Hospitalar , Transfusão de Sangue , Análise Multivariada , Plasma , Hipotermia Induzida
14.
Commun Biol ; 7(1): 836, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38982203

RESUMO

There is a dearth of statistical models that adequately capture the total signal attributed to whole-brain imaging features. The total signal is often widely distributed across the brain, with individual imaging features exhibiting small effect sizes for predicting neurobehavioral phenotypes. The challenge of capturing the total signal is compounded by the distribution of neurobehavioral data, particularly responses to psychological questionnaires, which often feature zero-inflated, highly skewed outcomes. To close this gap, we have developed a novel Variational Bayes algorithm that characterizes the total signal captured by whole-brain imaging features for zero-inflated outcomes. Our zero-inflated variance (ZIV) estimator estimates the fraction of variance explained (FVE) and the proportion of non-null effects (PNN) from large-scale imaging data. In simulations, ZIV demonstrates superior performance over other linear models. When applied to data from the Adolescent Brain Cognitive DevelopmentSM (ABCD) Study, we found that whole-brain imaging features contribute to a larger FVE for externalizing behaviors compared to internalizing behaviors. Moreover, focusing on features contributing to the PNN, ZIV estimator localized key neurocircuitry associated with neurobehavioral traits. To the best of our knowledge, the ZIV estimator is the first specialized method for analyzing zero-inflated neuroimaging data, enhancing future studies on brain-behavior relationships and improving the understanding of neurobehavioral disorders.


Assuntos
Encéfalo , Neuroimagem , Humanos , Encéfalo/diagnóstico por imagem , Neuroimagem/métodos , Adolescente , Algoritmos , Teorema de Bayes , Feminino , Masculino , Imageamento por Ressonância Magnética/métodos , Modelos Estatísticos , Criança
16.
medRxiv ; 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-39006419

RESUMO

Background: Treatment-resistant depression (TRD) is a major challenge in mental health, affecting a significant number of patients and leading to considerable economic and social burdens. The etiological factors contributing to TRD are complex and not fully understood. Objective: To investigate the genetic factors associated with TRD using polygenic scores (PGS) across various traits, and to explore their potential role in the etiology of TRD using large-scale genomic data from the All of Us Research Program (AoU). Methods: Data from 292,663 participants in the AoU were analyzed using a case-cohort design. Treatment resistant depression (TRD), treatment responsive Major Depressive Disorder (trMDD), and all others who have no formal diagnosis of Major Depressive Disorder (non-MDD) were identified through diagnostic codes and prescription patterns. Polygenic scores (PGS) for 61 unique traits from seven domains were used and logistic regressions were conducted to assess associations between PGS and TRD. Finally, Cox proportional hazard models were used to explore the predictive value of PGS for progression rate from the diagnostic event of Major Depressive Disorder (MDD) to TRD. Results: In the discovery set (104128 non-MDD, 16640 trMDD, and 4177 TRD), 44 of 61 selected PGS were found to be significantly associated with MDD, regardless of treatment responsiveness. Eleven of them were found to have stronger associations with TRD than with trMDD, encompassing PGS from domains in education, cognition, personality, sleep, and temperament. Genetic predisposition for insomnia and specific neuroticism traits were associated with increased TRD risk (OR range from 1.05 to 1.15), while higher education and intelligence scores were protective (ORs 0.88 and 0.91, respectively). These associations are consistent across two other independent sets within AoU (n = 104,388 and 63,330). Among 28,964 individuals tracked over time, 3,854 developed TRD within an average of 944 days (95% CI: 883 ~ 992 days) after MDD diagnosis. All eleven previously identified and replicated PGS were found to be modulating the conversion rate from MDD to TRD. Thus, those having higher education PGS would experiencing slower conversion rates than those who have lower education PGS with hazard ratios in 0.79 (80th versus 20th percentile, 95% CI: 0.74 ~ 0.85). Those who had higher insomnia PGS experience faster conversion rates than those who had lower insomnia PGS, with hazard ratios in 1.21 (80th versus 20th percentile, 95% CI: 1.13 ~ 1.30). Conclusions: Our results indicate that genetic predisposition related to neuroticism, cognitive function, and sleep patterns play a significant role in the development of TRD. These findings underscore the importance of considering genetic and psychosocial factors in managing and treating TRD. Future research should focus on integrating genetic data with clinical outcomes to enhance our understanding of pathways leading to treatment resistance.

17.
CJC Open ; 6(6): 830-835, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-39022173

RESUMO

The safety of continuing human epidermal growth factor receptor 2 (HER2)-targeted therapy in women with mild cardiotoxicity remains unclear. We performed a retrospective matched cohort study of 14 patients with human epidermal growth factor receptor 2-positive breast cancer receiving sequential anthracycline and trastuzumab therapy, nested within the Evaluation of Myocardial Changes During Breast Adenocarcinoma Therapy to Detect Cardiotoxicity Earlier With MRI (EMBRACE-MRI) trial. Among patients who developed cardiotoxicity and were treated with heart failure therapy, we compared those who had trastuzumab therapy interrupted to a matched cohort who continued trastuzumab therapy. By a median of 2.5 years of follow-up, no significant differences were present between the groups in the proportion with magnetic resonance imaging-measured left ventricular ejection fraction < 40%, magnetic resonance imaging-measured left ventricular volumes, left ventricular ejection fraction, edema, fibrotic markers, cardiopulmonary fitness, or quality of life.


La question de savoir s'il est sûr de poursuivre le traitement par un médicament ciblant le récepteur 2 du facteur de croissance épidermique humain (HER2) en présence d'une légère cardiotoxicité chez la femme demeure controversée. Nous avons réalisé une étude de cohortes appariées rétrospective auprès de 14 patientes atteintes d'un cancer du sein positif pour le HER2 qui recevaient un traitement séquentiel par l'anthracycline et le trastuzumab, dans le cadre du programme EMBRACE-MRI ( E valuation of M yocardial Changes During Br east A denocarcinoma Therapy to Detect C ardiotoxicity E arlier With MRI ). Parmi les patientes ayant développé une cardiotoxicité et ayant reçu un traitement pour l'insuffisance cardiaque, nous avons comparé celles dont le traitement par le trastuzumab a été interrompu à une cohorte appariée ayant poursuivi ce traitement. Après un suivi médian de 2,5 ans, aucune différence significative n'avait été observée entre les groupes en ce qui concerne le pourcentage de patientes dont la fraction d'éjection ventriculaire gauche était inférieure à 40 % à l'imagerie par résonance magnétique (IRM), le volume ventriculaire gauche à l'IRM, la fraction d'éjection ventriculaire gauche, l'œdème, les marqueurs fibrotiques, la bonne forme physique de l'appareil cardio-pulmonaire ou la qualité de vie.

18.
J Perinatol ; 2024 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-38851855

RESUMO

OBJECTIVE: Pumping studies in mothers of preterm infants are limited by self-reported pumping behaviors and non-objective measures of pumped milk volume and secretory activation (SA). METHODS: Non-randomized observational study of first 14 days postpartum in 29 mothers of preterm infants. Smart pumps measured and stored pumping behaviors and pumped milk volume. Selective ion electrodes measured sodium and sodium:potassium ratio to determine SA. Generalized estimating equations, cluster analyses and multivariate regression were used. RESULTS: SA was delayed (median 5.8 days) and impermanent. Each additional daily pumping increased odds of SA within 2 days by 48% (p = 0.01). High-intensity pumping mothers (N = 17) had greater daily and cumulative pumped milk volume than low-intensity pumping mothers (N = 12). Pumping variables showed daily changes in the first week, then plateaued. CONCLUSION: The first week postpartum is critical for optimizing pumping behaviors. Accurate, objective measures of pumping behaviors, pumped milk volume and SA are a research priority.

19.
J Magn Reson Imaging ; 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38940396

RESUMO

BACKGROUND: Cardiac MRI feature tracking (FT) allows objective assessment of segmental left ventricular (LV) function following a myocardial infarction (MI), but its utilization in sheep, where interventions can be tested, is lacking. PURPOSE: To apply and validate FT in a sheep model of MI and describe post-MI LV remodeling. STUDY TYPE: Animal model, longitudinal. ANIMAL MODEL: Eighteen lambs (6 months, male, n = 14; female, n = 4; 25.2 ± 4.5 kg). FIELD STRENGTH/SEQUENCE: Two-dimensional balanced steady-state free precession (bSSFP) and 3D inversion recovery fast low angle shot (IR-FLASH) sequences at 3 T. ASSESSMENT: Seven lambs underwent test-retest imaging to assess FT interstudy reproducibility. MI was induced in the remaining 11 by coronary ligation with MRI being undertaken before and 15 days post-MI. Injury size was measured by late gadolinium enhancement (LGE) and LV volumes, LV mass, ejection fraction (LVEF), and wall thickness (LVWT) were measured, with FT measures of global and segmental radial, circumferential, and longitudinal strain. STATISTICAL TESTS: Sampling variability, inter-study, intra and interobserver reproducibility were assessed using Pearson's correlation, Bland-Altman analyses, and intra-class correlation coefficients (ICC). Diagnostic performance of segmental strain to predict LGE was assessed using receiver operating characteristic curve analysis. Significant differences were considered P < 0.05. RESULTS: Inter-study reproducibility of FT was overall good to excellent, with global strain being more reproducible than segmental strain (ICC = 0.89-0.98 vs. 0.77-0.96). MI (4.0 ± 3.7% LV mass) led to LV remodeling, as evident by significantly increased LV volumes and LV mass, and significantly decreased LVWT in injured regions, while LVEF was preserved (54.9 ± 6.9% vs. 55.6 ± 5.7%; P = 0.778). Segmental circumferential strain (CS) correlated most strongly with LGE. Basal and mid- CS increased significantly, while apical CS significantly decreased post-MI. DATA CONCLUSION: FT is reproducible and compensation by hyperkinetic remote myocardium may manifest as overall preserved global LV function. EVIDENCE LEVEL: N/A TECHNICAL EFFICACY: Stage 2.

20.
J Med Screen ; : 9691413241260019, 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38869176

RESUMO

OBJECTIVES: Primary human papillomavirus (HPV) testing by clinician-collection is endorsed by U.S. guideline organizations for cervical cancer screening, but uptake remains low and insights into patients' understanding are limited. This study aims to primarily address patient awareness of primary HPV screening by clinician-collection and acceptance of primary HPV screening by clinician- and self-collection, and secondarily assess factors associated with awareness and acceptance. SETTING: Primary care practices affiliated with an academic medical center. METHODS: A cross-sectional survey study of screening-eligible women aged 30-65 years was conducted to assess awareness and acceptability of primary HPV screening. We analyzed bivariate associations of respondent characteristics with awareness of primary HPV screening by clinician-collection, willingness to have clinician- or self-collected primary HPV testing, and reasons for self-collection preference. RESULTS: Respondents (n = 351; response rate = 23.4%) reported cervical cancer screening adherence of 82.8% but awareness of clinician-collected primary HPV as an option was low (18.9%) and only associated with HPV testing with recent screening (p = 0.003). After reviewing a description of primary HPV screening, willingness for clinician-collected (81.8%) or home self-collected (76.1%) HPV testing was high, if recommended by a provider. Acceptability of clinician-collected HPV testing was associated with higher income (p = 0.009) and for self-collection was associated with higher income (p = 0.002) and higher education (p = 0.02). Higher education was associated with reporting self-collection as easier than clinic-collection (p = 0.02). Women expected self-collection to be more convenient (94%), less embarrassing (85%), easier (85%), and less painful (81%) than clinician-collection. CONCLUSIONS: Educational interventions are needed to address low awareness about the current clinician-collected primary HPV screening option and to prepare for anticipated federal licensure of self-collection kits. Informing women about self-collection allows them to recognize benefits which could address screening barriers.

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