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The gold-standard approaches for gleaning statistically valid conclusions from data involve random sampling from the population. Collecting properly randomized data, however, can be challenging, so modern statistical methods, including propensity score reweighting, aim to enable valid inferences when random sampling is not feasible. We put forth an approach for making inferences based on available data from a source population that may differ in composition in unknown ways from an eventual target population. Whereas propensity scoring requires a separate estimation procedure for each different target population, we show how to build a single estimator, based on source data alone, that allows for efficient and accurate estimates on any downstream target data. We demonstrate, theoretically and empirically, that our target-independent approach to inference, which we dub "universal adaptability," is competitive with target-specific approaches that rely on propensity scoring. Our approach builds on a surprising connection between the problem of inferences in unspecified target populations and the multicalibration problem, studied in the burgeoning field of algorithmic fairness. We show how the multicalibration framework can be employed to yield valid inferences from a single source population across a diverse set of target populations.
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Direct control of protein interactions by chemically induced protein proximity holds great potential for both cell and synthetic biology as well as therapeutic applications. Low toxicity, orthogonality and excellent cell permeability are important criteria for chemical inducers of proximity (CIPs), in particular for in vivo applications. Here, we present the use of the agrochemical mandipropamid (Mandi) as a highly efficient CIP in cell culture systems and living organisms. Mandi specifically induces complex formation between a sixfold mutant of the plant hormone receptor pyrabactin resistance 1 (PYR1) and abscisic acid insensitive (ABI). It is orthogonal to other plant hormone-based CIPs and rapamycin-based CIP systems. We demonstrate the applicability of the Mandi system for rapid and efficient protein translocation in mammalian cells and zebrafish embryos, protein network shuttling and manipulation of endogenous proteins.
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Amidas/farmacologia , Ácidos Carboxílicos/farmacologia , Fungicidas Industriais/farmacologia , Ácido Abscísico/metabolismo , Animais , Dimerização , Peixe-Zebra/embriologiaRESUMO
The study of a fluorescent indolin-3-one derivative is reported that, as opposed to its previously described congeners, selectively undergoes photoactivated ring-opening in apolar solvents. The excited state involved in this photoisomerization was partially deactivated by the formation of singlet oxygen. Cell studies revealed lipid droplet accumulation and efficient light-induced cytotoxicity.
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Oxigênio Singlete , SolventesRESUMO
BACKGROUND: Schizophrenia spectrum disorders (SSDs) are presumed to be associated with retinal thinning. However, evidence is lacking as to whether these retinal alterations reflect a disease-specific process or are rather a consequence of comorbid diseases or concomitant microvascular impairment. METHODS: The study included 126 eyes of 65 patients with SSDs and 143 eyes of 72 healthy controls. We examined macula and optic disc measures by optical coherence tomography (OCT) and OCT angiography (OCT-A). Additive mixed models were used to assess the impact of SSDs on retinal thickness and perfusion and to explore the association of retinal and clinical disease-related parameters by controlling for several ocular and systemic covariates (age, sex, spherical equivalent, intraocular pressure, body mass index, diabetes, hypertension, smoking status, and OCT signal strength). RESULTS: OCT revealed significantly lower parafoveal macular, macular ganglion cell-inner plexiform layer (GCIPL), and macular retinal nerve fiber layer (RNFL) thickness and thinner mean and superior peripapillary RNFL in SSDs. In contrast, the applied OCT-A investigations, which included macular and peripapillary perfusion density, macular vessel density, and size of the foveal avascular zone, did not reveal any significant between-group differences. Finally, a longer duration of illness and higher chlorpromazine equivalent doses were associated with lower parafoveal macular and macular RNFL thickness. CONCLUSIONS: This study strengthens the evidence for disease-related retinal thinning in SSDs.
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Disco Óptico , Esquizofrenia , Humanos , Tomografia de Coerência Óptica/métodos , Esquizofrenia/complicações , Esquizofrenia/diagnóstico por imagem , Células Ganglionares da Retina , Pressão IntraocularRESUMO
PURPOSE: To evaluate the effectiveness of 0.19-mg fluocinolone acetonide implant (FAi) for preventing inflammatory relapses in noninfectious uveitis with posterior segment involvement in standard clinical practice. Further, to assess the value of remission induction therapy with intraocular and periorbital administered high-dose corticosteroids before FAi. METHODS: A retrospective cohort study in a tertiary referral center specialized in uveitis management. The primary study outcomes were the best-corrected visual acuity (BVCA) and central retinal thickness (CRT) within a 12-month observation period. The secondary outcomes were intraocular pressure (IOP) and intraocular inflammation. The main safety measures were IOP increase and cataract formation. RESULTS: In total, 76 eyes of 57 patients received FAi. Locally administered high-dose corticosteroids were applied in 68.4% of all eyes before FAi. BCVA remained stable within the 12-month observation period (63.21 vs. 62.95, difference 0.26 letters; 95% CI: - 6.31 to 6.84; p > 0.9). Significant CRT reduction upon FAi was sustained after 12 months (362.7 vs. 309.1 µm, difference 53.57 µm; 95% CI: 1.55 to 105.6; p = 0.04). Intraocular inflammation was reduced until 9 months of follow-up (0.82 vs. 0.3, difference 0.53; 95% CI: 0.11 to 0.95; p = 0.007). A mean IOP increase (13.68 vs. 15.6; difference - 1.92; 95% CI: - 3.85 to 0.004; p = 0.0507) and cataract development (20% of all phakic eyes) were noted. CONCLUSION: We observed similar levels of FAi effectiveness for the treatment of noninfectious uveitis in standard clinical practice compared to previous randomized clinical trials. Moreover, remission induction therapy before FAi can benefit patients with increased baseline uveitis activity.
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Catarata , Uveíte Posterior , Uveíte , Humanos , Glucocorticoides , Estudos Retrospectivos , Implantes de Medicamento/uso terapêutico , Recidiva Local de Neoplasia , Fluocinolona Acetonida , Uveíte/diagnóstico , Uveíte/tratamento farmacológico , Uveíte/induzido quimicamente , Pressão Intraocular , Inflamação , Catarata/complicações , Catarata/diagnóstico , Resultado do Tratamento , Uveíte Posterior/diagnóstico , Uveíte Posterior/tratamento farmacológicoRESUMO
A titanium(III)-catalyzed desulfonylation gives access to functionalized alkyl nitrile building blocks from α-sulfonyl nitriles, circumventing traditional base-mediated α-alkylation conditions and strong single electron donors. The reaction tolerates numerous functional groups including free alcohols, esters, amides, and it can be applied also to the α-desulfonylation of ketones. In addition, a one-pot desulfonylative alkylation is demonstrated. Preliminary mechanistic studies indicate a catalyst-dependent mechanism involving a homolytic C-S cleavage.
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PURPOSE: Long total waiting times (TWT) experienced by patients during a clinic visit have a significant adverse effect on patient's satisfaction. Our aim was to use big data simulations of a patient scheduling calendar and its effect on TWT in a general ophthalmology clinic. Based on the simulation, we implemented changes to the calendar and verified their effect on TWT in clinical practice. DESIGN AND METHODS: For this retrospective simulation study, we generated a discrete event simulation (DES) model based on clinical timepoints of 4.401 visits to our clinic. All data points were exported from our clinical warehouse for further processing. If not available from the electronic health record, manual time measurements of the process were used. Various patient scheduling models were simulated and evaluated based on their reduction of TWT. The most promising model was implemented into clinical practice in 2017. RESULTS: During validation of our simulation model, we achieved a high agreement of mean TWT between the real data (229 ± 100 min) and the corresponding simulated data (225 ± 112 min). This indicates a high quality of the simulation model. Following the simulations, a patient scheduling calendar was introduced, which, compared with the old calendar, provided block intervals and extended time windows for patients. The simulated TWT of this model was 153 min. After implementation in clinical practice, TWT per patient in our general ophthalmology clinic has been reduced from 229 ± 100 to 183 ± 89 min. CONCLUSION: By implementing a big data simulation model, we have achieved a cost-neutral reduction of the mean TWT by 21%. Big data simulation enables users to evaluate variations to an existing system before implementation into clinical practice. Various models for improving patient flow or reducing capacity loads can be evaluated cost-effectively.
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Oftalmologia , Instituições de Assistência Ambulatorial , Agendamento de Consultas , Big Data , Humanos , Estudos RetrospectivosRESUMO
BACKGROUND: Guidelines and recommendations from public health authorities related to face masks have been essential in containing the COVID-19 pandemic. We assessed the prevalence and correlates of mask usage during the pandemic. METHODS: We examined a total of 13,723,810 responses to a daily cross-sectional online survey in 38 countries of people who completed from April 23, 2020 to October 31, 2020 and reported having been in public at least once during the last 7 days. The outcome was individual face mask usage in public settings, and the predictors were country fixed effects, country-level mask policy stringency, calendar time, individual sociodemographic factors, and health prevention behaviors. Associations were modeled using survey-weighted multivariable logistic regression. RESULTS: Mask-wearing varied over time and across the 38 countries. While some countries consistently showed high prevalence throughout, in other countries mask usage increased gradually, and a few other countries remained at low prevalence. Controlling for time and country fixed effects, sociodemographic factors (older age, female gender, education, urbanicity) and stricter mask-related policies were significantly associated with higher mask usage in public settings. Crucially, social behaviors considered risky in the context of the pandemic (going out to large events, restaurants, shopping centers, and socializing outside of the household) were associated with lower mask use. CONCLUSION: The decision to wear a face mask in public settings is significantly associated with sociodemographic factors, risky social behaviors, and mask policies. This has important implications for health prevention policies and messaging, including the potential need for more targeted policy and messaging design.
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COVID-19 , Pandemias , Idoso , Estudos Transversais , Feminino , Humanos , Máscaras , SARS-CoV-2RESUMO
PURPOSE: To determine the anatomical and functional outcomes of an extended 6-month intravitreal anti-vascular endothelial growth factor (anti-VEGF) upload in choroidal neovascularization (CNV) secondary to chronic central serous chorioretinopathy (CSCR). METHODS: A retrospective database analysis was performed applying the following inclusion criteria: (1) diagnosis of CSCR, (2) diagnosis of secondary CNV, and (3) treatment of at least six consecutive injections of anti-VEGF. Outcome measures included the change of central retinal subfield thickness, remodeling of the pigment epithelium detachments, and change in visual function. RESULTS: Twenty-one eyes of 21 patients were included. Mean patient age was 65 ± 8.3 years, and 35% of the patients (n = 8) were female. Mean disease duration before diagnosis of CNV was 48 ± 25.3 months. Mean central retinal thickness decreased from 346 ± 61 to 257 ± 57 µm (p < 0.01) after the sixth injection while mean visual acuity improved from 0.65 ± 0.35 to 0.49 ± 0.29 (logMAR; p < 0.01). Of note, an extended upload of six as opposed to three injections yielded an additional mean central retinal thickness reduction (280 ± 46 µm vs. 257 ± 57 µm, p = 0.038). Significant CNV remodeling was observed as a decrease in pigment epithelium detachment (PED) vertical (p = 0.021) and horizontal diameter (p = 0.024) as well as PED height (p < 0.01). CONCLUSION: An extended anti-VEGF upload of six consecutive injections seems to be effective in inducing CNV remodeling and fluid resorption in CNV complicating chronic CSCR.
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Inibidores da Angiogênese/uso terapêutico , Coriorretinopatia Serosa Central/complicações , Neovascularização de Coroide/tratamento farmacológico , Ranibizumab/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Neovascularização de Coroide/diagnóstico por imagem , Neovascularização de Coroide/etiologia , Neovascularização de Coroide/fisiopatologia , Corantes/administração & dosagem , Feminino , Angiofluoresceinografia , Humanos , Verde de Indocianina/administração & dosagem , Injeções Intravítreas , Masculino , Pessoa de Meia-Idade , Imagem Multimodal , Epitélio Pigmentado da Retina/fisiopatologia , Estudos Retrospectivos , Tomografia de Coerência Óptica , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Acuidade Visual/fisiologiaRESUMO
PURPOSE: To predict, by using machine learning, visual acuity (VA) at 3 and 12 months in patients with neovascular age-related macular degeneration (AMD) after initial upload of 3 anti-vascular endothelial growth factor (VEGF) injections. DESIGN: Database study. PARTICIPANTS: For the 3-month VA forecast, 653 patients (379 female) with 738 eyes and an average age of 74.1 years were included. The baseline VA before the first injection was 0.54 logarithm of the minimum angle of resolution (logMAR) (±0.39). A total of 456 of these patients (270 female, 508 eyes, average age: 74.2 years) had sufficient follow-up data to be included for a 12-month VA prediction. The baseline VA before the first injection was 0.56 logMAR (±0.42). METHODS: Five different machine-learning algorithms (AdaBoost.R2, Gradient Boosting, Random Forests, Extremely Randomized Trees, and Lasso) were used to predict VA in patients with neovascular AMD after treatment with 3 anti-VEGF injections. Clinical data features came from a data warehouse (DW) containing electronic medical records (41 features, e.g., VA) and measurement features from OCT (124 features, e.g., central retinal thickness). The VA of patient eyes excluded from machine learning was predicted and compared with the ground truth, namely, the actual VA of these patients as recorded in the DW. MAIN OUTCOME MEASURES: Difference in logMAR VA after 3 and 12 months upload phase between prediction and ground truth as defined. RESULTS: For the 3-month VA forecast, the difference between the prediction and ground truth was between 0.11 logMAR (5.5 letters) mean absolute error (MAE)/0.14 logMAR (7 letters) root mean square error (RMSE) and 0.18 logMAR (9 letters) MAE/0.2 logMAR (10 letters) RMSE. For the 12-month VA forecast, the difference between the prediction and ground truth was between 0.16 logMAR (8 letters) MAE/0.2 logMAR (10 letters) RMSE and 0.22 logMAR (11 letters) MAE/0.26 logMAR (13 letters) RMSE. The best performing algorithm was the Lasso protocol. CONCLUSIONS: Machine learning allowed VA to be predicted for 3 months with a comparable result to VA measurement reliability. For a forecast after 12 months of therapy, VA prediction may help to encourage patients adhering to intravitreal therapy.
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Inibidores da Angiogênese/uso terapêutico , Neovascularização de Coroide/tratamento farmacológico , Aprendizado de Máquina , Acuidade Visual/fisiologia , Degeneração Macular Exsudativa/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Neovascularização de Coroide/diagnóstico , Neovascularização de Coroide/fisiopatologia , Bases de Dados Factuais , Progressão da Doença , Feminino , Seguimentos , Humanos , Injeções Intravítreas , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Degeneração Macular Exsudativa/diagnóstico , Degeneração Macular Exsudativa/fisiopatologiaRESUMO
PURPOSE: We assessed differences in compliance and adherence (lateness of patients, visual acuity, reasons for abstaining) between patients with diabetic macular edema (DME) and patients with age-related macular degeneration (AMD), both under anti-vascular endothelial growth factor therapy. METHODS: We included 136 patients with DME (36% women, 65 years, 22 visits, 13.9 injections, and 29.9 months of follow-up) and 109 patients with AMD (59% women, 76 years, 20 visits, 14.7 injections, and 22.3 months of follow-up) (minimum follow-up of 12 months and at least 5 injections). We assessed missed appointments (lateness >14 days) and therapy break-offs (lateness >100 days). All delayed patients were called and interviewed for abstaining reasons. RESULTS: Forty-six percent of patients with DME and 22% of patients with AMD had at least one break-off. Thirty-five percent of patients with DME and 50% of patients with AMD were always on schedule. In patients with DME, there was significant correlation (P = 0.017) between the number of break-offs and change of visual acuity. In 60% DME and 38% AMD of break-off cases, visual acuity was worse than the before break-off. The most common reason for abstaining was comorbidities (33% AMD and 20% DME). CONCLUSION: There are significant differences between patients with AMD and DME regarding compliance and adherence, which also affects outcome. Strategies to tie patients with DME to costly intravitreal therapy need to be developed to improve outcomes and efficacy.
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Bevacizumab/administração & dosagem , Retinopatia Diabética/tratamento farmacológico , Macula Lutea/patologia , Edema Macular/tratamento farmacológico , Adesão à Medicação , Ranibizumab/administração & dosagem , Receptores de Fatores de Crescimento do Endotélio Vascular/administração & dosagem , Proteínas Recombinantes de Fusão/administração & dosagem , Idoso , Inibidores da Angiogênese/administração & dosagem , Retinopatia Diabética/complicações , Retinopatia Diabética/diagnóstico , Feminino , Seguimentos , Humanos , Injeções Intravítreas , Degeneração Macular/diagnóstico , Degeneração Macular/tratamento farmacológico , Edema Macular/diagnóstico , Edema Macular/etiologia , Masculino , Visita a Consultório Médico/estatística & dados numéricos , Cooperação do Paciente , Estudos Retrospectivos , Tomografia de Coerência Óptica , Resultado do Tratamento , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Acuidade VisualRESUMO
BACKGROUND: The purpose of this study was to identify differences in clinical corneal findings after standard and accelerated epithelial off cross-linking (CXL) during a long-term follow-up. METHODS: Two hundred forty-one patients (184 male) were included in this monocentric, retrospective, non-randomized and unmasked study. One hundred forty-eight eyes were treated with the accelerated protocol and 138 with the standard protocol with epithelial off CXL, if diagnosed with keratoconus and a progression in Kmax of more than one dioptre during the preceding 6 months, plus a minimal pachymetry measurement of 400 µm in keratometry (Pentacam, Oculus GmbH, Wetzlar, Germany). Exclusion criteria were previous surgery, other corneal conditions or age above 50 years. Follow-up time was 36 months with clinical examination and keratometry at every visit. Outcome measures were the observed rate of corneal changes, differences between treatment groups and correlation with keratometry measurements. RESULTS: In patients with accelerated CXL, significantly more clear corneas were seen at three (p = 0.015) and six (p = 0.002) months after surgery than following the standard protocol. The rate of clear corneas dropped from 52.2% pre-operation (OP) to a minimum of 19.3% after 6 months in the standard protocol group compared with 50.7% clear corneas pre-OP and a minimum of 40.8% in the accelerated group. In the standard protocol group, more striae were found 3 months after intervention than in the accelerated group (p = 0.05). CONCLUSIONS: In patients with accelerated CXL, fewer morphological corneal changes were observed than after conventional CXL. However, rarely, corneal changes persisted for a long time.
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Reagentes de Ligações Cruzadas/uso terapêutico , Ceratocone/tratamento farmacológico , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/uso terapêutico , Adulto , Protocolos Clínicos , Córnea/patologia , Feminino , Humanos , Ceratocone/patologia , Ceratocone/cirurgia , Masculino , Estudos Retrospectivos , Riboflavina/uso terapêuticoRESUMO
Background The importance of evaluating real-life data is constantly increasing. Currently available computer systems better allow for analyses of data, as more and more data is available in a digital form. Before a project for real-life data analyses is started, technical considerations and staff, legal, and data protection procedures need to be addressed. In this manuscript, experiences made at the University Eye Hospital in Munich will be shared. Materials and Methods Legal requirements, as found in laws and guidelines governing documentation and data privacy, are highlighted. Technical requirements for information technology infrastructure and software are defined. A survey conducted by the German Ophthalmological Society, among German eye hospitals investigating the current state of digitalization, was conducted. Also, staff requirements are outlined. Results A database comprising results of 330,801 patients was set up. It includes all diagnoses, procedures, clinical findings and results from diagnostic devices. This database was approved by the local data protection officer. In less than half of German eye hospitals (n = 21) that participated in the survey (n = 54), a complete electronic documentation is done. Fourteen institutions are completely paper-based, and the remainder of the hospitals used a mixed system. Conclusion In this work, we examined the framework that is required to develop a comprehensive database containing real-life data from clinics. In future, these databases will become increasingly important as more and more innovation are made in decision support systems. The base for this is comprehensive and well-curated databases.
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Bases de Dados Factuais/estatística & dados numéricos , Hospitais Especializados/estatística & dados numéricos , Hospitais Universitários/estatística & dados numéricos , Sistemas Computadorizados de Registros Médicos/estatística & dados numéricos , Oftalmologia/estatística & dados numéricos , Inteligência Artificial/legislação & jurisprudência , Inteligência Artificial/estatística & dados numéricos , Big Data , Transplante de Córnea , Bases de Dados Factuais/legislação & jurisprudência , Processamento Eletrônico de Dados/legislação & jurisprudência , Processamento Eletrônico de Dados/estatística & dados numéricos , Alemanha , Fidelidade a Diretrizes/legislação & jurisprudência , Fidelidade a Diretrizes/estatística & dados numéricos , Hospitais Especializados/legislação & jurisprudência , Hospitais Universitários/legislação & jurisprudência , Humanos , Aprendizado de Máquina/legislação & jurisprudência , Aprendizado de Máquina/estatística & dados numéricos , Sistemas Computadorizados de Registros Médicos/legislação & jurisprudência , Oftalmologia/legislação & jurisprudência , Sistemas de Informação em Radiologia/legislação & jurisprudência , Sistemas de Informação em Radiologia/estatística & dados numéricos , Design de Software , Bancos de Tecidos/legislação & jurisprudência , Bancos de Tecidos/estatística & dados numéricosRESUMO
The present prospective single-center study investigated the prognostic role of novel serum biomarkers in advanced pancreatic cancer (PC). Patients (pts) with locally advanced or metastatic PC treated with first-line palliative chemotherapy were included. Among others, the serum markers CYFRA 21-1, haptoglobin, serum-amyloid A (SAA), and 25-OH vitamin D3 were determined at baseline and categorized by pre-defined cut-offs [median values (MV), upper limits of normal (ULN), lower limits of normal (LLN), or the natural logarithm (ln)] and correlated with overall survival (OS). Among the 59 pts included, pre-treatment CYFRA 21-1 levels showed a strong correlation with OS independent of the applied cut-off (MV 4.9 ng/ml-14.2 vs. 4.2 months, HR 0.18, p = 0.001; ULN 3.3 ng/ml-14.2 vs. 4.4 months, HR 0.28, p = 0.003; [ln] CYFRA 21-1-HR 0.77, p = 0.013). Lower values of haptoglobin were additionally associated with an improvement in OS (categorized by LLN of 2.05 g/l-10.4 vs. 5.5 months, HR 0.46, p = 0.023; [ln] haptoglobin-HR 0.51, p = 0.036). Pts with baseline SAA values below the MV of 22 mg/l also had a prolonged OS (10.4 vs. 5.0 months, HR 0.47, p = 0.036). For 25-OH vitamin D3 levels, no significant correlation with OS was found. In multivariate analyses, pre-treatment CYFRA 21-1 levels (categorized by MV-HR 0.15, p = 0.032) as well as [ln] haptoglobin (HR 0.30, p = 0.006) retained their independent prognostic significance for OS. CYFRA 21-1, haptoglobin, and SAA might provide useful prognostic information in advanced PC. An external multicenter validation of these results is necessary.
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Antígenos de Neoplasias/sangue , Colecalciferol/sangue , Haptoglobinas , Queratina-19/sangue , Neoplasias Pancreáticas/sangue , Proteína Amiloide A Sérica , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Biomarcadores Tumorais/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Cuidados Paliativos , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Prognóstico , Análise de SobrevidaRESUMO
Differential item functioning (DIF) is a common challenge when examining latent traits in large scale surveys. In recent work, methods from the field of machine learning such as model-based recursive partitioning have been proposed to identify subgroups with DIF when little theoretical guidance and many potential subgroups are available. On this basis, we propose and compare recursive partitioning techniques for detecting DIF with a focus on measurement models with multiple latent variables and ordinal response data. We implement tree-based approaches for identifying subgroups that contribute to DIF in multidimensional latent variable modeling and propose a robust, yet scalable extension, inspired by random forests. The proposed techniques are applied and compared with simulations. We show that the proposed methods are able to efficiently detect DIF and allow to extract decision rules that lead to subgroups with well fitting models.
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OBJECTIVES: To determine real-life quantitative changes in OCT biomarkers in a large set of treatment naive patients in a real-life setting undergoing anti-VEGF therapy. For this purpose, we devised a novel deep learning based semantic segmentation algorithm providing the first benchmark results for automatic segmentation of 11 OCT features including biomarkers for neovascular age-related macular degeneration (nAMD). METHODS: Training of a Deep U-net based semantic segmentation ensemble algorithm for state-of-the-art semantic segmentation performance which was used to analyze OCT features prior to, after 3 and 12 months of anti-VEGF therapy. RESULTS: High F1 scores of almost 1.0 for neurosensory retina and subretinal fluid on a separate hold-out test set with unseen patients. The algorithm performed worse for subretinal hyperreflective material and fibrovascular PED, on par with drusenoid PED, and better in segmenting fibrosis. In the evaluation of treatment naive OCT scans, significant changes occurred for intraretinal fluid (mean: 0.03 µm3 to 0.01 µm3, p < 0.001), subretinal fluid (0.08 µm3 to 0.01 µm3, p < 0.001), subretinal hyperreflective material (0.02 µm3 to 0.01 µm3, p < 0.001), fibrovascular PED (0.12 µm3 to 0.09 µm3, p = 0.02) and central retinal thickness C0 (225.78 µm3 to 169.40 µm3). The amounts of intraretinal fluid, fibrovascular PED, and ERM were predictive of poor outcome. CONCLUSIONS: The segmentation algorithm allows efficient volumetric analysis of OCT scans. Anti-VEGF provokes most potent changes in the first 3 months while a gradual loss of RPE hints at a progressing decline of visual acuity. Additional research is required to understand how these accurate OCT predictions can be leveraged for a personalized therapy regimen.
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BACKGROUND: Optical coherence tomography and electroretinography studies have revealed structural and functional retinal alterations in individuals with schizophrenia spectrum disorders (SSDs). However, it remains unclear which specific retinal layers are affected; how the retina, brain, and clinical symptomatology are connected; and how alterations of the visual system are related to genetic disease risk. METHODS: Optical coherence tomography, electroretinography, and brain magnetic resonance imaging were applied to comprehensively investigate the visual system in a cohort of 103 patients with SSDs and 130 healthy control individuals. The sparse partial least squares algorithm was used to identify multivariate associations between clinical disease phenotype and biological alterations of the visual system. The association of the revealed patterns with individual polygenic disease risk for schizophrenia was explored in a post hoc analysis. In addition, covariate-adjusted case-control comparisons were performed for each individual optical coherence tomography and electroretinography parameter. RESULTS: The sparse partial least squares analysis yielded a phenotype-eye-brain signature of SSDs in which greater disease severity, longer duration of illness, and impaired cognition were associated with electrophysiological alterations and microstructural thinning of most retinal layers. Higher individual loading onto this disease-relevant signature of the visual system was significantly associated with elevated polygenic risk for schizophrenia. In case-control comparisons, patients with SSDs had lower macular thickness, thinner retinal nerve fiber and inner plexiform layers, less negative a-wave amplitude, and lower b-wave amplitude. CONCLUSIONS: This study demonstrates multimodal microstructural and electrophysiological retinal alterations in individuals with SSDs that are associated with disease severity and individual polygenic burden.
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PURPOSE: To evaluate the long-term outcomes of patients with non-infectious uveitis treated with 0.19 mg fluocinolone acetonide insert (FAi) for up to 36 months in clinical practice. METHODS: A retrospective study conducted at a single uveitis center. RESULTS: Fifty eyes of 39 patients were included. Mean best corrected visual acuity (BCVA) and central retinal thickness (CRT) remained stable until month 36 after FAi implantation (61.04 vs. 70.25 letters and 370.8 vs. 332.5 µm, respectively). The recurrence rate was 34% (17 eyes) after 36 months, of which 82% (14 eyes) received high-dose corticosteroids before FAi. Mean intraocular pressure (IOP) remained unchanged (13.38 vs. 15.74 mmHg), while most phakic eyes (13 of 14 eyes) required cataract surgery. CONCLUSIONS: We show that FAi effectively prevents recurrences of non-infectious uveitis for up to three years in clinical practice, comparable with randomized clinical trials. Patients who received high-dose corticosteroids before FAi have an increased risk for early recurrence and should be considered for scheduled re-treatment.
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The COVID-19 pandemic has spotlighted the importance of high-quality data for empirical health research and evidence-based political decision-making. To leverage the full potential of these data, a better understanding of the determinants and conditions under which people are willing to share their health data is critical. Building on the privacy theory of contextual integrity, the privacy calculus, and previous findings regarding different data types and recipients, we argue that established social norms shape the acceptance of novel practices of data collection and use. To investigate the willingness to share health data, we conducted a preregistered vignette experiment. The scenarios experimentally varied the vignette dimensions by data type, recipient, and research purpose. While some findings contradict our hypotheses, the results indicate that all three dimensions affected respondents' data sharing decisions. Additional analyses suggest that institutional and social trust, privacy concerns, technical affinity, altruism, age, and device ownership influence the willingness to share health data.
Assuntos
COVID-19 , Pandemias , Humanos , Prontuários Médicos , Biomarcadores , Disseminação de InformaçãoRESUMO
BACKGROUND: Humanitarian crises and armed conflicts lead to a greater prevalence of poor population mental health. Following the 1 February 2021 military coup in Burma, the country's civilians have faced humanitarian crises that have probably caused rising rates of mental disorders. However, a dearth of data has prevented researchers from assessing the extent of the problem empirically. AIMS: To better understand prevalence of depressive and anxiety disorders among the Burmese adult population after the February 2021 military coup. METHOD: We fielded an online non-probability survey of 7720 Burmese adults aged 18 and older during October 2021 and asked mental health and demographic questions. We used the Patient Health Questionnaire-4 to measure probable depression and anxiety in respondents. We also estimated logistic regressions to assess variations in probable depression and anxiety across demographic subgroups and by level of trust in various media sources, including those operated by the Burmese military establishment. RESULTS: We found consistently high rates of probable anxiety and depression combined (60.71%), probable depression (61%) and probable anxiety (58%) in the sample overall, as well as across demographic subgroups. Respondents who 'mostly' or 'completely' trusted military-affiliated media sources (about 3% of the sample) were significantly less likely than respondents who did not trust these sources to report symptoms of anxiety and depression (AOR = 0.574; 95% CI 0.370-0.889), depression (AOR = 0.590; 95% CI 0.383-0.908) or anxiety (AOR = 0.609; 95% CI 0.390-0.951). CONCLUSIONS: The widespread symptoms of anxiety and depression we observed demonstrate the need for both continuous surveillance of the current situation and humanitarian interventions to address mental health needs in Burma.