WRONGFUL BIRTH: A POSSIBILIDADE DE REPARAÇÃO CIVIL NOS CASOS DE TRISSOMIA DO CROMOSSOMO 21 NÃO DETECTADOS DURANTE A GESTAÇÃO

O presente trabalho discute a possibilidade de reparação civil nos casos de Síndrome de Down não detectados durante a gestação pelo profissional médico responsável pela assistência pré-natal, à luz do ordenamento jurídico brasileiro. Atualmente, com o avanço da tecnologia, tornou-se possível um diagnóstico pré-natal cada vez mais preciso. A detecção precoce de uma disfunção genética como a Síndrome de Down, permite aos futuros pais se prepararem emocional e financeiramente para a chegada do bebê e a buscarem informações sobre as peculiaridades advindas da aneuploidia. Em países onde o abordo é permitido, o wrongful birth versa sobre a perda da chance do exercício do direito de aborto. No Brasil, embora não exista no ordenamento jurídico a possibilidade de se interromper uma gravidez senão pelas exceções previstas em lei, é possível afirmar que essas ações ganham relevância na esfera cível. Com a constitucionalização do Direito, o avanço da ciência jurídica aliado à evolução da ciência médica e do desenvolvimento tecnológico surgiram novas modalidades de danos reparáveis, fato que obrigou o Poder Judiciário a alterar a sua estrutura jurisprudencial, refletindo na valorização da função compensatória e na necessidade de oferecer assistência à vítima do dano. Por essa razão, buscou-se por meio de pesquisa bibliografia, sustentar o cabimento da indenização pelo wrongful birth pelo erro de diagnóstico pré-natal, pois interfere diretamente no planejamento familiar dos futuros pais

A Network-Based Algorithm for Clustering Multivariate Repeated Measures Data

The National Aeronautics and Space Administration (NASA) Astronaut Corps is a unique occupational cohort for which vast amounts of measures data have been collected repeatedly in research or operational studies pre-, in-, and post-flight, as well as during multiple clinical care visits. In exploratory analyses aimed at generating hypotheses regarding physiological changes associated with spaceflight exposure, such as impaired vision, it is of interest to identify anomalies and trends across these expansive datasets. Multivariate clustering algorithms for repeated measures data may help parse the data to identify homogeneous groups of astronauts that have higher risks for a particular physiological change. However, available clustering methods may not be able to accommodate the complex data structures found in NASA data, since the methods often rely on strict model assumptions, require equally-spaced and balanced assessment times, cannot accommodate missing data or differing time scales across variables, and cannot process continuous and discrete data simultaneously. To fill this gap, we propose a network-based, multivariate clustering algorithm for repeated measures data that can be tailored to fit various research settings. Using simulated data, we demonstrate how our method can be used to identify patterns in complex data structures found in practice

Molecular imaging by micro-CT: specific E-selectin imaging

The primary goal of this study was to design a fluorescent E-selectin-targeted iodine-containing liposome for specific E-selectin imaging with the use of micro-CT. The secondary goal was to correlate the results of micro-CT imaging with other imaging techniques with cellular resolution, i.e., confocal and intravital microscopy. E-selectin-targeted liposomes were tested on endothelial cells in culture and in vivo in HT-29 tumor-bearing mice (n = 12). The liposomes contained iodine (as micro-CT contrast medium) and fluorophore (as optical contrast medium) for confocal and intravital microscopy. Optical imaging methods were used to confirm at the cellular level, the observations made with micro-CT. An ischemia-reperfusion model was used to trigger neovessel formation for intravital imaging. The E-selectin-targeted liposomes were avidly taken up by activated endothelial cells, whereas nontargeted liposomes were not. Direct binding of the E-selectin-targeted liposomes was proved by intravital microscopy, where bright spots clearly appeared on the activated vessels. Micro-CT imaging also demonstrated accumulation of the targeted lipsomes into subcutaneous tumor by an increase of 32 ± 8HU. Hence, internalization by activated endothelial cells was rapid and mediated by E-selectin. We conclude that micro-CT associated with specific molecular contrast agent is able to detect specific molecular markers on activated vessel walls in viv

Covid-19 Severity Scale For Claims Data Research

OBJECTIVE: to create and validate a methodology to assign a severity level to an episode of COVID-19 for retrospective analysis in claims data. DATA SOURCE: Secondary data obtained by license agreement from Optum provided claims records nationally for 19,761,754 persons, of which, 692,094 persons had COVID-19 in 2020. STUDY DESIGN: The World Health Organization (WHO) COVID-19 Progression Scale was used as a model to identify endpoints as measures of episode severity within claims data. Endpoints used included symptoms, respiratory status, progression to levels of treatment and mortality. DATA COLLECTION/EXTRACTION METHODS: The strategy for identification of cases relied upon the February 2020 guidance from the Centers for Disease Control and Prevention (CDC). PRINCIPAL FINDINGS: A total of 709,846 persons (3.6%) met the criteria for one of the nine severity levels based on diagnosis codes with 692,094 having confirmatory diagnoses. The rates for each level varied considerably by age groups, with the older age groups reaching higher severity levels at a higher rate. Mean and median costs increased as severity level increased. Statistical validation of the severity scales revealed that the rates for each level varied considerably by age group, with the older ages reaching higher severity levels (p \u3c 0.001). Other demographic factors such as race and ethnicity, geographic region, and comorbidity count had statistically significant associations with severity level of COVID-19. CONCLUSION: A standardized severity scale for use with claims data will allow researchers to evaluate episodes so that analyses can be conducted on the processes of intervention, effectiveness, efficiencies, costs and outcomes related to COVID-19

The comparative burden of mild, moderate and severe Fibromyalgia: results from a cross-sectional survey in the United States

<p>Abstract</p> <p>Background</p> <p>Fibromyalgia (FM) is characterized by chronic, widespread pain, fatigue, and other symptoms; yet few studies have comprehensively assessed its humanistic burden. This observational study evaluates the impact of FM severity on patients' symptoms, health-related quality of life (HRQoL), and productivity in the United States.</p> <p>Methods</p> <p>203 FM subjects were recruited from 20 physician offices. Subjects completed a questionnaire including the EuroQol 5D (EQ-5D), Fibromyalgia Impact Questionnaire (FIQ), Multidimensional Assessment of Fatigue (MAF), Medical Outcomes Study Sleep Scale (MOS-SS), and Hospital Anxiety and Depression Scale (HADS) and questions about demographics, pain and other symptoms, HRQoL and productivity. FIQ total scores were used to define FM severity, with 0- < 39, 39- < 59, and 59-100, representing mild, moderate, and severe FM, respectively. Sites recorded subjects' clinical characteristics and FM treatment on case report forms using medical records. Summary statistics were calculated for continuous variables and frequency distributions for categorical variables. Differences across FM severity groups were evaluated using the Kruskal-Wallis or Chi-square tests. Statistical significance was evaluated at the 0.05 level.</p> <p>Results</p> <p>Mean (SD) age was 47.9 (10.9); 95% were female. Most (92%) were prescribed medication for FM; 24% and 66% reported moderate and severe FM, respectively. Mean (SD) scores were: 6.3 (2.1) for pain intensity; 0.35 (0.35) for EQ-5D; 30.7 (14.2) for MAF; 57.5 (18.4) for MOS-SS Sleep Problems Index; 10.2 (4.8) for HADS anxiety and 9.4 (4.4) for HADS depression. Subjects with worse FM severity reported significantly increased pain severity, HRQoL, fatigue, sleep disturbance, anxiety and depression (p < 0.001). Overall, 50% of subjects reported some disruption in their employment due to FM; this differed across severity levels (p < 0.001). Employed subjects missed a mean (SD) of 1.8 (3.9) workdays during the past 4 weeks; this also differed across severity levels (p = 0.03).</p> <p>Conclusions</p> <p>FM imposes a substantial humanistic burden on patients in the United States, and leads to substantial productivity loss, despite treatment. This burden is higher among subjects with worse FM severity.</p

Detection efficacy of [89Zr]Zr-PSMA-617 PET/CT in [68Ga]Ga-PSMA-11 PET/CT-negative biochemical recurrence of prostate cancer

Rationale In patients with biochemical recurrence of prostate cancer (BCR), preliminary data suggest that prostate-specifc membrane antigen (PSMA) ligand radiotracers labeled with zirconium-89 (89Zr; half-life ~ 78.41 h), which allow imaging≥24 h post-injection, detect suspicious lesions that are missed when using tracers incorporating short-lived radionuclides. Materials and methods To confrm [ 89Zr]Zr-PSMA-617 positron emission tomography/computed tomography (PET/CT) detection efcacy regarding such lesions, and compare quality of 1-h, 24-h, and 48-h [ 89Zr]Zr-PSMA-617 scans, we retrospectively analyzed visual fndings and PET variables refecting lesional [ 89Zr]Zr-PSMA-617 uptake and lesion-to-background ratio. The cohort comprised 23 men with BCR post-prostatectomy, median (minimum–maximum) prostate-specifc antigen (PSA) 0.54 (0.11–2.50) ng/mL, and negative [ 68Ga]Ga-PSMA-11 scans 40±28 d earlier. Primary endpoints were percentages of patients with, and classifcations of, suspicious lesions. Results Altogether, 18/23 patients (78%) had 36 suspicious lesions (minimum–maximum per patient: 1–4) on both 24-h and 48-h scans (n=33 lesions) or only 48-h scans (n=3 lesions). Only one lesion appeared on a 1-h scan. Lesions putatively represented local recurrence in 11 cases, and nodal or bone metastasis in 21 or 4 cases, respectively; 1/1 lesion was histologically confrmed as a nodal metastasis. In all 15 patients given radiotherapy based on [ 89Zr]Zr-PSMA-617 PET/CT, PSA values decreased after this treatment. Comparison of PET variables in 24-h vs 48-h scans suggested no clear superiority of either regarding radiotracer uptake, but improved lesion-to-background ratio at 48 h. Conclusions In men with BCR and low PSA, [ 89Zr]Zr-PSMA-617 PET/CT seems efective in fnding prostate malignancy not seen on [ 68Ga]Ga-PSMA-11 PET/CT. The higher detection rates and lesion-to-background ratios of 48-h scans versus 24-h scans suggest that imaging at the later time may be preferable. Prospective study of [ 89Zr]Zr-PSMA-617 PET/CT is warranted

Tumor Sink Effect with Prostate-Specific Membrane Antigen-Targeted Theranostics in Patients with Metastatic Castration-Resistant Prostate Cancer: Intra-Individual Evaluations

“Tumor sink effects”, decreased physiological uptake of radiopharmaceuticals due to sequestration by a tumor, may impact radioligand therapy (RLT) toxicity and dosing. We investigated these effects with prostate-specific membrane antigen (PSMA)-targeted radiopharmaceuticals in the healthy organs-at-risk (the parotid glands, kidneys, liver, and spleen) of 33 patients with metastatic castration-resistant prostate cancer (mCRPC). We retrospectively performed three intra-individual comparisons. First, we correlated changes from baseline to post-RLT (after two 177-lutetium (177Lu)-PSMA-617 cycles) in total lesional PSMA (∆TLP) and organ mean standardized uptake values (∆SUVmean). Second, in 25 RLT responders, we compared the organ SUVmean post-RLT versus that at baseline. Lastly, we correlated the baseline TLP and organ SUVmean. Data were acquired via 68-gallium-PSMA-11 positron emission tomography before the first and after the second 177Lu-PSMA-617 cycle. In the parotid glands and spleen, ∆TLP and ∆SUVmean showed a significant inverse correlation (r = −0.40, p = 0.023 and r = −0.36, p = 0.042, respectively). Additionally, in those tissues, the median organ SUVmean rose significantly from baseline after the response to RLT (p ≤ 0.022), and the baseline TLP and SUVmean were significantly negatively correlated (r = −0.44, p = 0.01 and r = −0.42, p = 0.016, respectively). These observations suggest tumor sink effects with PSMA-targeted radiopharmaceuticals in the salivary glands and spleen of patients with mCRPC

Burden of Illness Associated with Peripheral and Central Neuropathic Pain among Adults Seeking Treatment in the U nited S tates: A Patient‐Centered Evaluation

Objective The aim of this study was to evaluate patient‐reported burden associated with peripheral and central neuropathic pain ( NeP ) by pain severity and NeP condition. Design Six hundred twenty‐four subjects with one of six NeP conditions were recruited during routine office visits. Subjects consented to retrospective chart review and completed a one‐time questionnaire (including E uro Q ol‐5 dimensions, 12‐item S hort‐ F orm H ealth S urvey, B rief P ain I nventory‐ S hort F orm, M edical O utcomes S tudy S leep S cale, H ospital A nxiety and D epression S cale, and demographic and clinical characteristics). Pain severity scores were used to stratify subjects by mild, moderate, and severe pain. Summary statistics and frequency distributions were calculated. Differences by severity level were compared using K ruskal– W allis (continuous variables) and chi‐square or F isher's exact test (categorical variables). Effect size was computed with C ohen's d (mild vs severe). Results Subjects' mean age was 55.5. The majority (80.8%) had moderate or severe pain. Patient‐reported outcomes (health status, physical and mental health, pain interference with function, sleep, anxiety, and depression) were significantly worse among subjects with greater pain severity (all P  0.95) for all others. The observed burden was most substantial among chronic low back pain‐ NeP , although the pattern of disease burden was similar across the six NeP conditions. Conclusions Subjects across NeP conditions exhibited high pain levels, which were significantly associated with poor function, compromised health status and sleep, and increased anxiety and depression. Results indicate substantial patient burden across broad NeP , particularly among subjects with severe pain.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/109996/1/pme12502.pd

The SAMI Galaxy Survey: Revising the Fraction of Slow Rotators in IFS Galaxy Surveys

The fraction of galaxies supported by internal rotation compared to galaxies stabilized by internal pressure provides a strong constraint on galaxy formation models. In integral field spectroscopy surveys, this fraction is biased because survey instruments typically only trace the inner parts of the most massive galaxies. We present aperture corrections for the two most widely used stellar kinematic quantities $V/\sigma$ and $\lambda_{R}$. Our demonstration involves integral field data from the SAMI Galaxy Survey and the ATLAS$^{\rm{3D}}$ Survey. We find a tight relation for both $V/\sigma$ and $\lambda_{R}$ when measured in different apertures that can be used as a linear transformation as a function of radius, i.e., a first-order aperture correction. We find that $V/\sigma$ and $\lambda_{R}$ radial growth curves are well approximated by second order polynomials. By only fitting the inner profile (0.5$R_{\rm{e}}$), we successfully recover the profile out to one $R_{\rm{e}}$ if a constraint between the linear and quadratic parameter in the fit is applied. However, the aperture corrections for $V/\sigma$ and $\lambda_{R}$ derived by extrapolating the profiles perform as well as applying a first-order correction. With our aperture-corrected $\lambda_{R}$ measurements, we find that the fraction of slow rotating galaxies increases with stellar mass. For galaxies with $\log M_{*}/M_{\odot}>$ 11, the fraction of slow rotators is $35.9\pm4.3$ percent, but is underestimated if galaxies without coverage beyond one $R_{\rm{e}}$ are not included in the sample ($24.2\pm5.3$ percent). With measurements out to the largest aperture radius the slow rotator fraction is similar as compared to using aperture corrected values ($38.3\pm4.4$ percent). Thus, aperture effects can significantly bias stellar kinematic IFS studies, but this bias can now be removed with the method outlined here.Comment: Accepted for Publication in the Monthly Notices of the Royal Astronomical Society. 16 pages and 11 figures. The key figures of the paper are: 1, 4, 9, and 1