bluuebunny/crossref_metadata_2025_split huggingface dataset:
Is Aducanumab Treatment that Developed to Prevent Progression of Alzheimer's Disease Cost-Effective?
Authors: Yigit Vahit , Kalender Selin , Cetinturk Iskender 
Published: September 2022

Abstract
Background
Alzheimer's Disease (AD), the most common type of dementia, is a chronic, progressive, and neurodegenerative brain discomfort that causes the be damage to brain cells. Although there is no definitive treatment for AD, various drug treatments are used to reduce and control the symptoms of the disease. Developed for the treatment of mild-stage Alzheimer's patients, Aducanumab is the only drug approved by the Food and Drug Administration (FDA) in the past two decades. However, the cost is very high and, in many countries, Aducanumab has not been approved due to insufficient clinical efficacy and lack of evidence yet. This study aims to analyze the cost-effectiveness of Aducanumab, which was developed for the treatment of mild-stage AD, from the patient's perspective.
Methods
In the study, the Markov model was developed to determine the cost-effectiveness of Aducanumab compared to Standard of Care (SoC) therapy over a 5-year horizon. Cost and effectiveness data were taken from the literature. In the study, the discount rate was determined as 6%. The results were presented as the incremental cost-effectiveness ratio (ICER), which represents the cost per quality-adjusted life years (QALY). The results were retested with one-way and probabilistic sensitivity analysis due to possible uncertainties in the research parameters. The results were presented with the tornado diagram and the scatter plots.
Results
With the Markov model, the total costs of Aducanumab and SoC treatments over a 5-year horizon were found to be 98.068 $ and 21.292 $, respectively. Aducanumab treatment had an additional gain of 0.64 QALY and an additional cost of 76.776 $ compared to the SoC treatment. The ICER value, which shows the additional cost per QALY of Aducanumab, was 119.408 $/QALY. As a result of the study, it was determined that Aducanumab was not cost-effective when compared to SoC treatment. Sensitivity analysis results showed stability. Aducanumab was confirmed not to be cost-effective with its current price and potential clinical benefit.
Conclusion
The result of the research is considered important in terms of providing evidence-based information on the cost-effectiveness of Aducanumab in Turkey. However, further, research is needed to evaluate Aducanumab's clinical efficacy and cost-effectiveness.
Ethnoracial Representation in Hidradenitis Suppurativa Clinical Trials
Authors: Elhage Kareem G. , Davis Mitchell S. , Hakimi Marwa , Spencer Riley K. , Jin Joy Q. , Yeroushalmi Samuel , Chung Mimi , Bartholomew Erin , Bhutani Tina , Liao Wilson 
Published: September 2022

Abstract
Background
Hidradenitis suppurativa (HS) is an inflammatory skin disorder characterized by recurring painful and suppurating lesions. The global prevalence of HS is reported to be up to 4.10% in some countries, with the disease disproportionately affecting black populations. Ethnoracial representation in clinical trials is vital to ensuring results are generalizable. The purpose of this study is to examine whether ethnic or racial disparities exist in HS clinical trials.
Methods
The US National Library of Medicine clinical trials database (clinicaltrials.gov) was queried to identify HS clinical trials. Trials that did not present ethnic or racial data on either the website or publication were not considered.
Results
A total of 57 HS trials were identified. Of these, 23 trials, containing 2530 patients, included racial or ethnic data (Table 1). White patients made up 76.1% (1435/1886) of the study population, followed by Blacks or African Americans (13.7% (238/1732)), Hispanics or Latinos (7.2% (20/279), Asians (2.6% (26/1016)), American Indians or Alaska Natives (1.3% (14/1051)), and Native Hawaiians or Other Pacific Islanders (0.4% (4/926)).
Discussion
Our results establish a significant lack of minority ethnoracial representation in HS clinical trials. Since HS prevalence is highest among Blacks or African Americans, it is imperative that future clinical trials are conducted with a larger proportion of this population. Furthermore, clinical trials that did not report racial or ethnic information were conducted in countries with predominantly White populations, which likely skewed the results of this study and caused underreporting of these patients.
Longitudinal Course of Cognitive Impairment in Patients with Atopic Dermatitis
Authors: Jackson-Cowan Ladonya , Silverberg Jonathan I. 
Published: September 2022

Abstract
Cognitive dysfunction was recently demonstrated to be increased in adults and children with atopic dermatitis (AD). Though, little is known about the longitudinal course of cognitive impairment in AD and its relationship with pruritus. In order to investigate this, we conducted a prospective dermatology practice-based study using questionnaires and evaluation by a dermatologist (n = 210). Patients with ≥ 2 visits were included (mean follow-up time: 318 days). Cognitive function was assessed using the Patient-Reported Outcomes Measurement Information System (PROMIS) Cognitive Function 8-item Short-Form. At baseline, 20.85% of patients had PROMIS T-scores ≤ 45, indicating cognitive impairment (CI). More than half (59.09%) had CI at ≥ 1 follow-up visit; only 0.25% had CI at ≥ 2 follow-up visits. Among patients with CI at baseline, 34.09% had persistent CI, 47.71% had a fluctuating course and 18.18% had sustained improvement of cognitive function. In repeated measures regression models, cognitive function scores declined overtime in patients with worse AD severity (SCORing Atopic Dermatitis [SCORAD]: p = 0.01, Atopic Dermatitis Severity Index [ADSI]: p = 0.001), increased itch (p = 0.01), skin pain (p < 0.001), and sleep disturbance (p = 0.001). In multivariable logistic regression models, persistent CI were associated with depressive symptoms (moderate to severe Patient Health Questionnaire-9 score (PHQ9). Latent class analysis identified 2 classes of cognitive dysfunction: normal (77.23%), moderate dysfunction (16.21%) and severe impairment (6.55%). Patients of Black/African American race (p = 0.02) were more likely to have moderate dysfunction or severe cognitive impairment. In conclusion, AD is associated with a heterogeneous longitudinal course of cognitive function in adults, with some patients experiencing persistent CI over time.
Hipercolesterolemia Familiar: Relato De Caso
Authors: Correa Sidnei , Cristine Marques dos Santos Sara , Picone Borges de Aragão Ivana 
Published: September 2022

A hipercolesteromia familiar (HF) é uma doença genética autossômica dominante, expressada por níveis muito altos de colesterol total (CT), fração de lipoproteínas de baixa densidade de colesterol (low density lipoprotein - LDL-c) no plasma, depósito extravascular de colesterol e risco cardiovascular (CV) elevado, prematuro. Geralmente, nos pacientes hetereozigotos evidencia-se valores de CT entre 350 e 550mg/dl, enquanto nos homozigotos entre 650 e 1000mg/dl. Apesar de ser uma doença comum e com risco elevado de morte, é subdiagnosticada e subtratada, tendo em vista a concomitância de outros fatores de risco (FR) CV em comum com portadores de doença arterial coronariana (DAC). A diretriz recomenda o rastreio universal dos pacientes com CT elevado aos 20 anos e o rastreio em cascata. Para singularizar o diagnóstico, adotou-se o critério Dutch Lipid Clinic Network. A terapia dietética junto as estatinas de alta potência são a primeira escolha de tratamento, podendo associar o ezetimiba e anticorpo monoclonal alirucumabe i-PCSK9 em casos refratários. A associação dos três pode chegar a 85% de redução no LDL-c, reduzindo morbimortalidade na HF. A Hipertrigliceridemia (HTG) grave, com valores acima de 885mg/dl de triglicérides, não exclui o diagnóstico de HF e resulta em risco CV independente, além do risco de pancreatite aguda. O paciente do presente relato manteve níveis homozigotos de CT e HTG grave ao longo de anos, sem diagnóstico de HF e sem a terapia farmacológica necessária, com diversos eventos relacionados às DCVs e pancreatite aguda. Após 16 anos, recebeu prescrição de terapia tripla para controle de HF.
Ceratocone: uma revisão quanto ao diagnóstico e tratamento
Authors: Oliveira Bhiannca , Oliveira Delgado Mota Lívia 
Published: September 2022

Ceratocone é uma doença que afeta a córnea, essa é um tecido do olho humano que apura a qualidade da imagem produzida na retina. Constitui-se de uma membrana convexa, translúcida, inervada, sensível, sendo o único tecido avascular do corpo humano que se situa na parte anterior do globo ocular. Foi realizada uma revisão sistemática da literatura, com base em 20 artigos escolhidos por sua importância, relevância e dados levantados, variando entre os anos de 1945 e 2019, com o uso dos bancos de dados Scielo, Pubmed e Lilacs. Bem como o uso da tomografia da córnea e do segmento anterior, estudada por Bruno de Freitas Valbon, et al. , parece ser um método eficaz para aumentar a sensibilidade e a especificidade do diagnóstico e detecção precoce da ectasia corneana do tipo ceratocone. Como também, Bernardo Teixeira Lopes, et al. , estudou o perfil de espessura horizontal detectando o ceratocone, com capacidade comparável aos índices mais complexos. O diagnóstico do ceratocone abrange uma cuidadosa análise da córnea, abrangendo mecanismos simples aos mais complexos. Já o tratamento, destaca-se o crosslinking como método terapêutico efetivo, até o transplante de córnea nos últimos casos.
Perfil Epidemiológico de Idosos Internados por Fratura de Fêmur no Brasil
Authors: Abdala Lima Jessica , Pin Salles Lineker , Mendes da Silva Marcos Alex 
Published: September 2022

A fratura proximal de fêmur em idosos, na maioria das vezes, é consequência de quedas, sendo considerada uma importante causa de morbimortalidade nessa população e muitas vezes está relacionada a outras comorbidades preexistentes. Neste estudo, foi realizada uma revisão de literatura por meio de busca na base de dados do DATASUS- Sistema de Informações Hospitalares/Sistema único de Saúde (SIH/SUS) no período de 2012 a 2019. O objetivo do estudo foi conhecer o caráter epidemiológico envolvido nas internações dessa fratura em idosos de acordo com as cinco regiões brasileiras. Nesse sentido pretendeu-se correlacionar a epidemiologia atual com os resultados encontrados na tentativa de esclarecer o padrão de acometimento de tal ocorrência, por meio da relação entre variáveis como sexo, faixa etária, caráter atendimentos, custos em saúde, óbitos, entre outros. O estudo mostrou que o perfil de internações e óbitos encontrado teve predominância no sexo feminino e raça branca, sendo que esses aumentavam com a idade. Foi possível concluir que em decorrência do avanço da expectativa de vida aumentou-se a prevalência de internações devido à fratura de fêmur nos idosos, o que tem gerado elevado custo à saúde pública. Sendo necessário um controle a fim de prevenir os fatores de risco para quedas nessa população.
Palavras- chave: fratura de quadril, epidemiologia, idoso, brasil.
Insuficiência Valvar Aórtica por Valva Quadricúspide
Authors: Juliano Anna Vitória Ferreira Gonçalves , Cariolita Japiassu Moraes Brenda , Araújo Nascimento Bruno , Veiga Moneró Edgar , Neves Vilas Boas Guimarães Isecke Fernanda 
Published: September 2022

Resumo
A valva aórtica quadricúspide (VAQ) é uma anomalia congênita de achado raro, com probabilidade de desenvolver complicações para os pacientes com o decorrer da idade1,3. Pode ser achado ocasional em pacientes assintomáticos, mas, frequentemente, está associada com regurgitação aórtica podendo resultar em hipertensão pulmonar, hipertrofia moderada e dilatação leve. Recentemente, a ecocardiografia transesofágica (ETE) tem permitido um diagnóstico precoce, rápido e preciso quando há achados de VAQ. A presente pesquisa trata-se de busca bibliográfica em: publicações científicas, artigos científicos e revistas de publicação científica, usando o banco de dados Pubmed e SciELO no período de 2002 a 2019. Foi analisado que a VAQ é uma malformação congênita de valva aórtica extremamente rara com incidência entre 0,008 e 0,043%1. Pacientes com VAQ isolada normalmente são assintomáticos até por volta da quinta à sexta décadas de vida, idade em que valva se torna mais ineficiente3. Portanto, constata-se que a valva quadricúspide é uma anomalia anatômica que pode ocasionar principalmente insuficiência valvar e regurgitação aórtica. Porém, quando diagnosticada precocemente, possui um tratamento eficaz e preciso que melhora a qualidade de vida do paciente e evita complicações futuras.

Palavras-Chave: válvula aórtica quadricúspide, ECG, variação anatômica
Application of Membrane Processes for Nitrate (NO3-) Removal
Authors: Arar Özgür , Mehenktaş Cesur 
Published: September 2022

Background:The primary sources of nitrate contamination in groundwater resources are excessive fertilizer use and unregulated land discharges of treated wastewater. Due to its harmful nature to human health and its contribution to eutrophication, the removal of nitrate from water has been of great interest in the last decades. Various techniques, such as adsorption, ion exchange, catalytic and biological denitrification, and membrane processes, have been applied for NO3 - removal.Objective:In this review study, the removal of NO3 - by membrane processes, including electrodialysis (ED), electrodeionization (EDI), reverse osmosis (RO), and ultrafiltration, has been reviewed.Method:The pressure-driven membrane and electro-membrane processes applications to NO3 - removal have been reviewed.Results:The effects of process parameters, interferences, and limitations of membrane processes have been summarized.Conclusion:Membrane processes could be a promising alternative for NO3 - removal. After suitable membrane preparation/modification, the nitrate removal rate could reach >99%.
Newly Appearing Hepatic Lesion After Curative Surgery For Colorectal
Cancer: Single-phase CT Findings Implying Metastasis
Authors: Kim Dong Kyu , Jung Jae Hyeop , Kim Jin Kyem , Kim Taeho 
Published: September 2022

Background:
In patients treated with curative surgery for colorectal cancer, the single-phase (portal phase) abdomen-pelvic computed tomography (CT) follow-up is routinely performed to detect any recurrent lesions.

Objective:
To evaluate CT features implying metastasis in newly appearing hepatic lesions on single-phase CT after colorectal cancer surgery.

Method:
Of 1,227 patients who underwent curative colorectal surgery between 2011 and 2014, 267 patients with new hepatic lesions on follow-up single-phase CT (metastasis, n=192; benign, n=75) were included. The CT features of the hepatic lesions were analyzed by two radiologists, retrospectively, and clinical information including carcinoembryonic antigen (CEA) level was also reviewed. The risk factors for hepatic metastasis were evaluated by multivariable logistic regression.

Results:
In this study, independent CT features associated with metastasis were spherical shape (p < 0.001), circumscribed margin (p = 0.021), heterogeneous attenuation (p = 0.024) and bulging appearance (p = 0.007). Among the clinical factors, increased CEA level (p = 0.013), higher preoperative stage (p = 0.014) and lymphovascular invasion (p = 0.003) were associated with metastasis. However, on multivariable analysis, spherical shape was the only significant predictive factor for hepatic metastasis. The diagnostic performance of ‘spherical shape’ for detection of hepatic metastasis showed accuracy of 84.6%, sensitivity of 83.9%, and specificity of 86.7%.

Conclusion:
Specific single-phase CT features could be useful in distinguishing hepatic metastasis from benign, resulting in continuing routine CT follow-up without liver magnetic resonance imaging (MRI) when metastasis is unlikely.
Multitargeting Strategy Using Tetrathiomolybdate and Lenvatinib: Maximizing Antiangiogenesis
Activity in a Preclinical Liver Cancer Model
Authors: Nan Li , Yonghui Huang , Yuan Wan , Guodong Chen 
Published: September 2022

Purpose:
The study aims to investigate the suppressing tumor-promoting effects via multi-anti-angiogenesis
activity of the copper chelator (ammonium tetrathiomolybdate, TM) combined with lenvatinib for hepatocellular carcinoma.

Methods:
A total of 55 C57 mice were injected subcutaneously with Hepa1-6 hepatoma cell suspensions into the right
posterior thigh. After 7 days, the subcutaneous tumors were formed, and the mice were randomly divided into five
groups: TM (G1), Lenvatinib (G2), TM+Lenvatinib (G3), Control (G4), and Copper (II) Gluconate (G5). The copper
concentrations in serum and tumors were measured at the predetermined time points. After 14 days of treatments,
tumor weight and volumes were analyzed, histology was observed, and the expressions of vascular endothelial growth
factor (VEGF) and microvessel density (MVD) in tumor tissues were measured by immunohistochemistry.

Results:
The median concentration of copper in serum was 401.70, 469.40, and 665.35 μg/L in normal mice, in mice 7
days after implantation, and in the control group, respectively. The intratumoral copper concentrations were higher in
G4 mice than in mice 7 days after implantation (P < 0.05). The serum concentration of copper was higher in G5 than
all the other groups (P < 0.05; (G1, G2, and G3) vs. G4, P < 0.05; G1 vs. G2, P = 0.013; G2 vs. G3, P = 0.018; G1 vs.
G3, P = 0.903. The intratumoral copper concentrations were 608.40, 980.00, 539.31, and 2938.90 μg/L in G1, G2, G3,
and G5, respectively. The average tumor weight was 0.55, 0.44, 0.08, 1.37, and 3.11 in G1, G2, G3, G4, and G5, respectively.
G5 vs. other groups, P < 0.05; (G1, G2, and G3) vs. G4, P < 0.05; G1 vs. G3, P < 0.05; G2 vs. G3, P < 0.05;
G1 vs. G2, P > 0.05. Furthermore, the expression levels of VEGF were significantly lower in G1, G2, and G3 than in
G4 and G5 (P < 0.05). A similar trend was observed for MVD in the five groups, but no significant difference was
detected in G1 and G2.

Conclusion:
The study showed a significant positive correlation between tumor load and copper. Copper promotes
tumor progression, but copper chelating suppresses tumor growth. The combination of TM with lenvatinib reduces
tumor angiogenesis and improves the effect of antitumor treatment. These findings underlie the clinical application of
combination therapy.
Leprosy Reactions: Clinical Pharmacologist Perspective with Repurposed
Medications
Authors: Thangaraju Pugazhenthan , Balan Aravind Kumar , Velmurugan Hemasri , Venkatesan Sajitha , Yella Sree Sudha Tanguturi 
Published: September 2022

Abstract:
The elimination of leprosy has been possible with the available anti-leprotic drugs. However,
the lepra reactions usually occur months or years after multi-drug therapy completion, and continue
to be a formidable challenge mainly owing to its role in causing nerve damage and disability. Corticosteroids
are commonly used but they lead to systemic complications, and hence require dose reduction
and adjunct therapy with a different target. Various drugs with different targets have been identified
and are in practice to treat lepra reactions. The newer targets can include genetic and tissue targets in
the skin and nerve. Thalidomide treatment reducing pentraxin-3, toll-like receptor antagonists, minocycline,
apremilast, immunomodulators, and tenidap can be helpful in lepra reaction. Other modalities
to manage lepra reactions include plasma exchange, intravenous immunoglobulins, and immunotherapy.
Most of these treatments are based only on the pathological process of the reaction and tend to be
incomplete leading to recurrence. Newer multimodal approaches are required based on various biomarkers
(genetic, tissue, serological), which can be monitored to prevent the recurrence of reactions.
Hence, there is a need for newer targets and drugs to be identified for the management of lepra reactions.
“Buena madera”: significaciones asociadas con la genética reproductiva
Authors: Lima Natacha Salomé 
Published: September 2022

<p class="p2">La cantidad de tratamientos de reproducción asistida con gametos (óvulos y/o espermatozoides) <em>donados </em>ha aumentado progresivamente. A partir de la sanción del Código Civil y Comercial (2015), las tecnologías reproductivas se convirtieron en una nueva fuente de filiación con características propias, como la obligación de inscribir el nacimiento del/a nacido/a de donación de gametos. Las parejas heterosexuales tienden a omitir esta información con mayor frecuencia. Esa omisión puede responder a distintos motivos, miedos e inseguridades. Las recomendaciones psicológicas tienen como objetivo acompañar a los receptores de gametos para contribuir en la elaboración del <em>duelo </em>por la pérdida del aporte genético. Este trabajo explora las condiciones y sentidos vinculados con el <em>duelo genético </em>a partir de analizar las significaciones asociadas con la genética reproductiva en un subgrupo de mujeres cis heterosexuales que, según criterios de la medicina reproductiva, presentan edad materna avanzada (mayores de 40 años). Desde 2004, las mujeres que buscan un embarazo luego de los 40 años constituyen un subgrupo que registra un aumento de casos, convirtiendo la edad en la primera causa para recurrir a óvulos donados en Argentina (Mackey <em>et al</em>. 2020; Zegers <em>et al</em>. 2021). Los resultados son congruentes con otras investigaciones y demuestran que el modo de significar el origen genético depende de la conformación familiar, de las trayectorias (no)reproductivas y del paso del tiempo, donde el componente genético tiende a relativizarse en pos de la crianza y el vínculo compartido en la gestación, el amamantamiento y el parto. Aparecieron dos instancias en las que el gameto donado adquiere una condición “amenazante”, una es ante una posible enfermedad futura en el nacido y la otra por la obligación de registrar el nacimiento.<span class="Apple-converted-space"> </span></p>
Tecnologias de reprodução assistida, regulação e monoparentalidade: entre a autonomia e o individualismo
Authors: Oliva Augusto Maria Helena , Mendosa Douglas 
Published: September 2022

<p class="p2">O aumento de pessoas que realizam o desejo de ter filhos com o auxílio das tecnologias de reprodução assistida é um fato que tem sido objeto de inúmeras pesquisas no mundo inteiro. No Brasil, essa realidade é marcada pela ausência de uma lei específica sobre o tema. Em seu lugar, o Conselho Federal de Medicina (CFM) publica normas de orientação ética (resoluções) que sofreram contínuas alterações desde 1992, ano da primeira resolução. O objetivo deste artigo é o de apresentar como o processo de modificações dessas normas ao longo do tempo está relacionado à ampliação do acesso às TRA no Brasil. São essas mesmas técnicas que têm permitido, nos últimos anos, o aumento de pessoas solteiras, especialmente as mulheres, a realizarem o desejo de ter filhos de modo independente. Em função do caráter social de qualquer tecnologia, discute-se como a expansão das TRAS configuram e são configuradas por tendências das sociedades contemporâneas como a valorização da autonomia feminina (empoderamento) e o individualismo.<span class="Apple-converted-space"> </span></p>