bluuebunny/crossref_metadata_2025 huggingface dataset:
Interactions of antitumor triazoloacridinones with DNA.
Authors: Koba Marcin , Konopa Jerzy
Published: November 2019

Triazoloacridinones (TA) are a new group of potent antitumor compounds, from which the most active derivative, C-1305, has been selected for extended preclinical trials. This study investigated the mechanism of TA binding to DNA. Initially, for selected six TA derivatives differing in chemical structures as well as cytotoxicity and antitumor activity, the capability of noncovalent DNA binding was analyzed. We showed that all triazoloacridinones studied stabilized the DNA duplex at a low-concentration buffer but not at a salt concentration corresponding to that in cells. DNA viscometric studies suggested that intercalation to DNA did not play a major role in the mechanism of the cytotoxic action of TA. Studies involving cultured cells revealed that triazoloacridinone C-1305 after previous metabolic activation induced the formation of interstrand crosslinks in DNA of some tumor and fibroblast cells in a dose dependent manner. However, the detection of crosslink formation was possible only when the activity of topoisomerase II in cells was lowered. Furthermore, it was impossible to validate the relevance of the ability to crosslink DNA to biological activity of TA derivatives.
Occurrence of neoxanthin and lutein epoxide cycle in parasitic Cuscuta species.
Authors: Kruk Jerzy , Szymańska Renata
Published: November 2019

In the present study, xanthophyll composition of eight parasitic Cuscuta species under different light conditions was investigated. Neoxanthin was not detected in four of the eight species examined, while in others it occurred at the level of several percent of total xanthophylls. In C. gronovii and C. lupuliformis it was additionally found that the neoxanthin content was considerably stimulated by strong light. In dark-adapted plants, lutein epoxide level amounted to 10-22% of total xanthophylls in only three species, the highest being for C. lupuliformis, while in others it was below 3%, indicating that the lutein epoxide cycle is limited to only certain Cuscuta species. The obtained data also indicate that the presence of the lutein epoxide cycle and of neoxanthin is independent and variable among the Cuscuta species. The xanthophyll cycle carotenoids violaxanthin, antheraxanthin and zeaxanthin were identified in all the examined species and occurred at the level found in other higher plants. The xanthophyll and lutein epoxide cycle pigments showed typical response to high light stress. The obtained results also suggest that the ability of higher plants to synthesize lutein epoxide probably does not depend on the substrate specificity of zeaxanthin epoxidase but on the availability of lutein for the enzyme.
Differential binding of hyaluronan on the surface of tissue-specific endothelial cell lines.
Authors: Szczepanek Karol , Kieda Claudine , Cichy Joanna
Published: November 2019

Tissue-specific heterogeneity of endothelial cells, both structural and functional, plays a crucial role in physiologic as well as pathologic processes, including inflammation, autoimmune diseases and tumor metastasis. This heterogeneity primarily results from the differential expression of adhesion molecules that are involved in the interactions between endothelium and circulating immune cells or disseminating tumor cells. Among these molecules present on endothelial cells is hyaluronan (HA), a glycosaminoglycan that contributes to primary (rolling) interactions through binding to its main receptor CD44 expressed on leukocytes and tumor cells. While the regulation of CD44 expression and function on either leukocytes or tumor cells has been well characterized, much less is known about the ability of endothelial cells to express HA on their surface. Therefore, in these studies we analyzed HA levels on tissue-specific endothelium. We used endothelial cell lines of different origin, including lung, skin, gut and lymph nodes that had been established previously as model lines to study interactions between the endothelium and leukocytes/tumor cells. Our results indicate that HA is accumulated on the surface of all endothelial cells examined. Moreover, retention of endogenous HA differs between the lines and may depend on their tissue origin. Analysis of binding of exogenous HA reveals the presence of specific HA binding sites on all endothelial cell lines tested. However, the retention of endogenous HA and the binding of exogenous HA is mediated through a CD44-independent mechanism.
Changing How We Approach Multicultural Counselor Education: Using Intersectionality, Power, Privilege, and Oppression to Frame Lived Experiences
Authors: Pebdani Roxanna Nasseri
Published: November 2019

Historically, multicultural counselor education has taken a groups approach to educating students about cultural differences. Groups approaches explain cultural differences broadly, potentially leading students to minimize the potential for intra-group differences. This has led to the marginalization of the experiences of students with racial/ethnic minority identities. Incorporating the concepts of power, privilege, and oppression, along with the concept of intersectionality can allow multicultural educators to approach multicultural counselor education in a way that includes all students from any identity. These concepts, along with regularly addressed concepts like identity development, microaggressions, and advocacy, can lead to a broader view of cultural competency. Additionally, when students understand cultural competency within this framework, they have the tools to become lifelong learners. This approach allows students to learn about different client identities and cultures as they are encountered in the students' counseling experiences or as they evolve.
Facilitating Application of the Multicultural Counseling Competencies
Authors: Wilson Keith B. , Pitt Jenelle S. , Acklin Carrie L. , Gines Jason E. , Chao Si-Yi , Stewart James F.
Published: November 2019

Diverse people living throughout the world have existed for many centuries. Perhaps, the United States may have one of the most diverse populations in recent memory. There are indications that human service organizations need to be more accessible when underrepresented groups either seek, or are in the pipeline of providers. To facilitate outcomes of all populations, we assert that the Multicultural Counseling Competencies (MCC) model that deals with awareness, knowledge, and skills should emphasize theapplicationconcept more. We operationalizedcognitive, behaviorandaction, andapplicationterms and applied these terms to the MCC in extensive examples. Additionally, we highlight that the use of the termsbehaviorandactionare mistakenly conflated to meanapplication. Thus, decreasing application principles in the MCC. Future research and recommendations are highlighted.
The Multicultural Counseling Competencies: An Empirical Investigation
Authors: Wilson Keith B. , Acklin Carrie L. , Chao Si-Yi , Pitt Jennelle S. , Gines Jason E.
Published: November 2019

While the Multicultural Counseling Competencies (MCC) can be used for all populations, there is a gap between Awareness: Attitudes and Belief, Knowledge, Skills, and Application. As many underrepresented groups are increasingly becoming a major part of the demographic transformation, being culturally competent is critical. We examined the cognitive, behavior/action, and application categories in both the 1996 and 2016 MCC. Thus, we discovered more cognitive and behavioral/action than application statements in both the 1996 and 2016 MCC. Recommendations and implications are discussed.
ANALISIS KUALITAS SINYAL WIFI PADA UNIVERSITAS MUSLIM INDONESIA
Authors: Alwi Erick Irawadi
Published: November 2019

Indonesian Muslim universities utilize WiFi networks as a facility to support the implementation of student and academic lecture activities within the scope of Indonesian Muslim universities. However, with the number of Indonesian Muslim University students around 17,000 people, internet access to the internet network has become slow. In addition, there are several faculties on several floors that do not get wifi signals or get weak signals so students cannot enjoy the internet network. Because it is necessary to measure the signal quality on wireless devices (AP) in each faculty in the scope of UMI with action research methods and analyze the signal quality so that it is known what factors can cause the wifi signal to sometimes be weak or not even get a signal at all
Traditions of S.T. Coleridge’s ‘The Rime of the Ancient Mariner’ in ‘The Ballad of Reading Gaol’ by O. Wilde
Authors: Zhatkin Dmitry Nikolayevich , Ryabova Anna A.
Published: November 2019

This article aims to analyse the poetic traditions of The Rime of the Ancient Mariner by S.T. Coleridge, which migrated into The Ballad of Reading Gaol by O. Wilde. A comparative analysis of original poems and their Russian translations reveals a thematic and structural link that connects these two poems. The article highlights the common features and the differences in literary devices used by Coleridge and Wilde to transmit the complex concepts of suffering and forgiveness through their characters and to declare values and philosophical ideas. The literary devices in point define how these concepts are covered, and serve a common theme in the work of Coleridge and Wilde. The article also provides arguments to confirm the social situation described in the works.

The lyrico-epic genre allows using both poetry analysis tools and prose research methods, which ensures high-quality research.

The article frames values of the modern culture and creates conditions for discovering a conceptual similarity in the symbolism of The Rime of the Ancient Mariner and The Ballad of Reading Gaol.
Korelasi Sifat-Sifat Agronomi dengan Hasil dan Kandungan Antosianin Padi Beras Merah
Authors: Prabowo Hafidh , Djoar Djati Waluyo , Parjanto Parjanto
Published: November 2019

Brown rice is a type of rice can be grown on land that is less water (upland). Brown rice has anthocyanin as an antioxidant. The purpose of this study was to identify brown rice agronomics characters that can be used as selection criteria to obtain brown rice which high anthocyanin. The experiment was conducted at the greenhouse of Agriculture Faculty, UNS using completed randomized block design consisting of 5 local varieties namely Mandel Wonogiri, Segreng Gunung Kidul, Segreng Boyolali, Segreng Wonogiri 1, and Segreng Wonogiri 2. Analysis of the data using the model Singh and Chaudhary (1979) are displayed in the form of a matrix correlation. Anthocyanin assays using the differential pH test method. The results showed that there was no difference between the anthocyanin content of varieties, but there is a tendency Segreng Boyolali varieties containing anthocyanins and Mandel Wonogiri higher. In general, varieties tested showed different potential yield, except Mandel Wonogiri varieties have low yield. The character of the total number of tillers, panicle length, and number of panicles per hill showed a strong correlation coefficient with the results. Plant height, number of panicles per hill, and the weight of 1000 seeds showed a high correlation coefficient with anthocyanin content.
Microsurgery for Brachial Plexus Injury Before Versus After 6 Months of Age
Authors: Bauer Andrea S. , Kalish Leslie A. , Adamczyk Mark J. , Bae Donald S. , Cornwall Roger , James Michelle A. , Lightdale-Miric Nina , Peljovich Allan E. , Waters Peter M. ,   on behalf of the Treatment and Outcomes of Brachial Plexus Injury (TOBI) Study Group
Published: November 2019

Background:

Infants with more severe brachial plexus birth injury (BPBI) benefit from primary nerve surgery to improve function. The timing of the surgery, however, is controversial. The Treatment and Outcomes of Brachial Plexus Injury (TOBI) study is a multicenter prospective study with the primary aim of determining the optimal timing of this surgical intervention. This study compared outcomes evaluated 18 to 36 months after “early” microsurgery (at <6 months of age) with the outcomes of “late” microsurgery (at >6 months of age).

Methods:

Of 216 patients who had undergone microsurgery, 118 were eligible for inclusion because they had had a nerve graft and/or transfer followed by at least 1 physical examination during the 18 to 36-month interval after the microsurgery but before any secondary surgery. Patients were grouped according to whether the surgery had been performed before or after 6 months of age. Postoperative outcomes were measured using the total Active Movement Scale (AMS) score as well as the change in the AMS score. To address hand reinnervation, we calculated a hand function subscore from the AMS hand items and repeated the analysis only for the subjects with a Narakas grade of 3 or 4. Our hypothesis was that microsurgery done before 6 months of age would lead to better clinical outcomes than microsurgery performed after 6 months of age.

Results:

Eighty subjects (68%) had early surgery (at a mean age of 4.2 months), and 38 (32%) had late surgery (at a mean age of 10.7 months and a maximum age of 22.0 months). Infants who underwent early surgery presented earlier in life, had more severe injuries at baseline, and had a significantly lower postoperative AMS scores in the unadjusted analysis. However, when we controlled for the severity of the injury, the difference in the AMS scores between the early and late surgery groups was not significant. Similarly, when we restricted our multivariable analysis to patients with a Narakas grade-3 or 4 injury, there was no significant difference in the postoperative AMS hand subscore between the early and late groups.

Conclusions:

This study suggests that surgery earlier in infancy (at a mean age of 4.2 months) does not lead to better postoperative outcomes of BPBI nerve surgery than when the surgery is performed later in infancy (mean age of 10.7 months).

Level of Evidence:

Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.
Anterolateral Complex Reconstruction Augmentation of Anterior Cruciate Ligament Reconstruction
Authors: Lau Brian C. , Rames Jess , Belay Elshaday , Riboh Jonathan C. , Amendola Annunziato , Lassiter Tally
Published: November 2019

» Injury to the anterolateral complex may be identified on advanced imaging and may manifest with a higher level of instability, in particular with pivot-shift testing.

» The anterolateral ligament reconstruction or modified Lemaire procedure may be used to reconstruct the anterolateral complex of the knee to augment anterior cruciate ligament (ACL) reconstruction.

» Indications for anterolateral ligament reconstruction are evolving, but relative indications include revision ACL reconstruction, grade-III pivot shift, generalized ligamentous laxity, young age (<20 years), or high-level or high-demand athlete.

» Early outcomes have suggested that anterolateral ligament augmentation of ACL reconstruction may decrease the risk of re-tear of the ACL reconstruction.
Efectos de la dosificación y partes de plantas de Petiveria alliacea utilizado como fitobióticos sobre el crecimiento, digestibilidad de nutrientes y perfil sanguíneo de los polluelos
Authors: Muhammad S.B. , Sobayo R.A. , Oso A.O. , Sogunle O.M. , Ayoola A.A. , Adeyemo Y.O. , Basiru Y.T.
Published: November 2019

Os estudos sobre as inter-relações endocrinológicas em bovinos da Raça Brava de Lide são raros, permanecendo ainda incompreendidos todos os mecanismos que concorrem para a sua agressividade. A forma como a deficiência de testosterona ajusta exactamente o metabolismo do colesterol e da vasopressina permanece incerto. Foram estudados 10 touros da Raça Brava de Lide, dos quais, logo após o abate, foi recolhido e analisado o sangue, com o objectivo de se determinar os níveis de Testosterona, Colesterol e Vasopressina (ADH). Verifica-se uma conjunção de valores baixos de colesterol, altos de testosterona e de ADH, coincidentes com uma maior agressividade. A correlação da ADH vs testosterona é positiva e significativa ao nível de 5%. As médias encontradas para o Colesterol Total, a Testosterona Sérica e a ADH são respectivamente de – 139,4 mg/dL, 14,14 ng/dL e de 440,7 pg/ml. E, surge uma putativa correlação evidente, entre a Testosterona Sérica acima de 10,4 ng/dL e o Comportamento dos touros, qualificados com maior agressividade.
Proteomics profiling and pathway analysis of hippocampal aging in rhesus monkeys
Authors: Meng Shu , Xia Wenchao , Pan Meng , Jia Yangjie , He Zhanlong , Ge Wei
Published: November 2019

Background: Aged rhesus monkeys exhibit deficits in memory mediated by the hippocampus. Although extensive research has been carried out on the characteristics of human hippocampal aging, there is still very little scientific understanding of the changes associated with hippocampal aging in rhesus monkeys. To explore the proteomics profiling and pathway-related changes in the rhesus hippocampus during the aging process, we conducted a high throughput quantitative proteomics analysis of hippocampal samples from two groups of rhesus macaques aged 6 years and 20 years, using 2-plex tandem mass tag (TMT) labeling. In addition, we used a comprehensive bioinformatics analysis approach to investigate the enriched signaling pathways of differentially expressed proteins (the ratios of 20-y vs. 6-y, ≥1.20 or ≤ 0.83). Results: In total, 3,260 proteins were identified with a high level of confidence in rhesus hippocampus. We found 367 differentially expressed proteins related to rhesus hippocampus aging. Based on biological pathway analysis, we found these aging-related proteins were predominantly enriched in the electron transport chain, NRF2 pathway, focal adhesion-PI3K-AKT-mTOR signaling pathway and cytoplasmic ribosome proteins. Data are available via ProteomeXchange with identifier PXD011398. Conclusion: This study provides a detail description of the proteomics profile related to rhesus hippocampal aging. These findings should make an important contribution to further mechanistic studies, marker selection and drug development for the prevention and treatment of aging or age-related neurodegeneration.
The transfer of knowledge on integrated care among five European regions: a qualitative multi-method study
Authors: Grooten Liset , Vrijhoef Hubertus Johannes Maria , Alhambra-Borrás Tamara , Whitehouse Diane , Devroey Dirk
Published: November 2019

Background To examine how the knowledge transfer processes unfolded within SCIROCCO, a EU funded project (3rd Health Programme (2014-2020)) that aimed to facilitate the process of knowledge sharing across five European regions, to speed up adoption and scaling-up of integrated care initiatives.
Methods A qualitative multi-method design was used. Data collection methods included focus groups, project documents and action plans of the regions. The data was analysed using a qualitative content-analysis procedure, which was guided by the frameworks of knowledge exchange and the why, whose, what, how framework for knowledge mobilisers
Results All five components (including the themes) of knowledge exchange could be identified in the approach developed on the knowledge transfer processes. The four questions and accompanying categories of the framework of knowledge mobilisation were also identified to a large degree.
Conclusions The observed incorporation of distinct forms of knowledge from multiple sources and the observed dynamic and fluid knowledge transfer processes both suggest that SCIROCCO developed a comprehensive knowledge transfer approach aiming to enable the adoption and scaling-up of integrated care. Overall, the multi-method qualitative nature of this research has allowed some new and practical insights in the knowledge transfer activities on integrated care between several European regions. To obtain a clear understanding of the content of the knowledge transfer approaches, which could assist the operationalising of models to support the evaluation of knowledge transfer activities, it is strongly recommended that further research of this type should be conducted in other research settings.
Daily Almond Consumption in Cardiovascular Disease Prevention via LDL-C Change in the U.S. Population: a Cost-Effectiveness Analysis
Authors: Author) Jifan Wang(New Corresponding , Bravatti Michelle A. Lee , Johnson Elizabeth J. , Author) Gowri Raman(Former Corresponding
Published: November 2019

Objectives Heart disease is the leading cause of death in the United States. The U.S. Food and Drug Administration approved the health claim that 1.5 ounces (42.5 grams) of nut intake may reduce the risk of cardiovascular disease (CVD). Previous studies have focused on the cost-effectiveness of other foods or dietary factors on primary CVD prevention, yet not in almond consumption. This study aimed to examine the cost-effectiveness of almond consumption in CVD primary prevention.
Perspective & Setting This study assessed the cost-effectiveness of consuming 42.5 grams of almond from the U.S. healthcare sector perspective.
Methods A decision model was developed for 42.5 grams of almond per day versus no almond consumption and CVD in the U.S. population. Parameters in the model were derived from the literature, which included the probabilities of increasing LDL-C, developing acute myocardial infarction (MI) and stroke, treating MI, dying from the disease and surgery, as well as the costs of the disease and procedures in the U.S. population, and the quality-adjusted life years (QALY). The cost of almonds was based on the current price in the U.S. market. Sensitivity analyses were conducted for different levels of willingness-to-pay, the probabilistic sensitivity analysis, ten-year risk prevention, different costs of procedures and almond prices, and patients with or without CVD.
Results The almond strategy had $363 lower cost and 0.02 higher QALY gain compared to the non-almond strategy in the base-case model. The annual net monetary benefit (NMB) of almond consumption was $1,421 higher per person than no almond consumption, when the willingness to pay threshold was set at $50,000 for annual health care expenditure. Almond was more cost-effective than non-almond in CVD prevention in all the sensitivity analyses.
Conclusion Consuming 42.5 grams of almonds per day is a cost-effective approach to prevent CVD in the short term and potentially in the long term.
Integration of mental health care in private not-for-profit health centres in Guinea, West Africa: a systemic entry point towards the delivery of more patient-centred care?
Authors: Sow Abdoulaye , De Man Jeroen , De Spiegelaere Myriam , Vanlerberghe Veerle , Criel Bart
Published: November 2019

Background: Patient-centred care is an essential component of quality of health care. We hypothesize that integration of a mental health care package into versatile first-line health care services can strengthen patient participation, an important dimension of patient-centred care. The objective of this study is to analyse whether consultations conducted by providers in facilities that integrated mental health care score higher in terms of patient participation. Methods: This study was conducted in Guinea in 12 not-for-profit health centres, 4 of which had integrated a mental health care package (MH+) and 8 had not (MH-). The study involved 450 general curative consultations (175 in MH+ and 275 in MH- centres), conducted by 18 care providers (7 in MH+ and 11 in MH- centres). Patients were interviewed after the consultation on how they perceived their involvement in the consultation, using the Patient Participation Scale (PPS). The providers completed a self-administered questionnaire on their perception of patient’s involvement in the consultation. We compared scores of the PPS between MH+ and MH- facilities and between patients and providers. Results: The mean PPS score was 24.21 and 22.54 in MH+ and MH- health centres, respectively. Participation scores depended on both care providers and the health centres they work in. The patients consulting an MH+ centre were scoring higher on patient participation score than the ones of an MH- centre (adjusted odds ratio of 4.06 with a 95% CI of 1.17-14.10, p = 0.03). All care providers agreed they understood the patients' concerns, and patients shared this view. All patients agreed they wanted to be involved in the decision-making concerning their treatment; providers, however, were reluctant to do so. Conclusion: Integrating a mental health care package into versatile first-line health services can promote more patient-centred care . Key words: Mental health. Quality of care. Patient-centred care. Patient participation. Not-for-profit health centres. Guinea.
Systemic treatment of hormone receptor positive, human epidermal growth factor 2 negative metastatic breast cancer: retrospective analysis from Leeds Cancer Centre
Authors: Twelves Chris , Cheeseman Sue , Sopwith Will , Thompson Matthew , Riaz Majid , Ahat-Donker Necibe , Myland Melissa , Lee Adam , Przybysz Raymond , Turner Stuart , Hall Geoff , Perren Tim
Published: November 2019

BACKGROUND Study aimed to characterise treatment and outcomes for patients with hormone receptor positive (HR+), human epidermal growth factor 2 negative (HER2-) metastatic breast cancer (MBC) within a large regional cancer centre, as a benchmark for evaluating real-world impact of novel therapies such as CDK4/6 inhibitors.METHODS Retrospective longitudinal cohort, using electronic patient records of adult females with a first diagnosis of HR+/HER2- MBC January 2012 - March 2018.RESULTS 196 women were identified with HR+/HER2- MBC. Median age was 67 years, 85.2% were post-menopausal and median time between primary diagnosis and metastasis was 5.4 years. Most (75.1%) patients received endocrine therapy as first line systemic treatment (1st LoT); use of 1st LoT chemotherapy halved between 2012 and 2017. Patients receiving 1st LoT chemotherapy were younger and more likely to have visceral metastasis ( p <0.01). Median OS was 29.5 months and significantly greater for patients with exclusively non-visceral metastasis ( p <0.01). The adjusted hazard ratio for death of patients with visceral (or CNS) metastasis was 1.91 relative to those with exclusively non-visceral metastasis.CONCLUSIONS Diverse endocrine therapies predominate as 1st LoT for patients with HR+/HER2- MBC, chemotherapy being associated with more aggressive disease in younger patients, emphasising the importance of using effective and tolerable therapies early.
The impact of obstetric interventions and complications on women’s satisfaction with childbirth - a population based cohort study including 16000 women.
Authors: Falk Maja , Nelson Marie , Blomberg Marie
Published: November 2019

Background: As a quality marker and a tool for benchmarking between units, a visual analogue scale (VAS) (ranging from 1 to 10) to estimate woman’s satisfaction with childbirth was introduced in 2014. This study aimed to assess how obstetric interventions and complications affected women’s satisfaction with childbirth.

Methods: A retrospective cohort study including 16775 women with an available VAS score who gave birth between January 2016 and December 2017. VAS score, maternal and obstetric characteristics were obtained from electronic medical records and crude and adjusted odds ratios (aOR) were calculated.

Results: The total prevalence of dissatisfaction with childbirth (VAS 1-3) was 5.7%. The main risk factors for dissatisfaction with childbirth were emergency cesarean section, aOR 3.98 95% confidence interval (CI) 3.27-4.86, postpartum hemorrhage ³2000 ml, aOR 1.85 95%CI 1.24-2.76 and Apgar score <7 at five minutes, aOR 2.95 95%CI 1.95-4.47. The amount of postpartum hemorrhage showed a dose-response relation to dissatisfaction with childbirth. Moreover, labor induction, instrumental vaginal delivery, and obstetric anal sphincter injury were significantly associated with women´s dissatisfaction with childbirth. A total number of 4429/21204 (21%) women giving birth during the study period had missing values on VAS. A comparison of characteristics between women with and without a recorded VAS score was performed. There were statistically significant differences in maternal age and maternal BMI between the study population and excluded women due to missing values on VAS. Moreover, 64% of the women excluded were multiparas, compared to 59% in the study population.

Conclusions: Obstetric interventions and complications, including emergency cesareans section and postpartum hemorrhage, were significantly related to dissatisfaction with childbirth.

Such events are common and awareness of these associations might lead to a more individualized care of women during and after childbirth.
Intravenous recombinant tissue-type plasminogen activator thrombolysis for acute central retinal artery occlusion: a meta-analysis
Authors: Wang Xiaotang , Liu Yong , Suo Yan , Qin Dan , Meng Qiang , Zhang Yanchun , Zhang Hua , Wang Ying
Published: November 2019

Background: Central retinal artery occlusion (CRAO), an ocular stroke, causes severe and permanent visual impairment. Thrombolytic therapy is currently the main treatment option for CRAO. Intravenous thrombolysis with recombinant tissue-type plasminogen activator (rt-PA) has been extensively applied in the treatment of CRAO with the proven advantages of effectiveness and safety. This meta-analysis aimed to assess the efficacy of intravenous rt-PA thrombolysis for the management of CRAO by evaluating the pooled evidence. Methods: A comprehensive literature search of electronic databases including PubMed, OVID, and Cochrane Library was conducted up to and including March 2019. All studies reporting visual outcomes after CRAO (with thrombolytic therapy) were collected. Patient-level data on visual acuity (VA) and adverse events were recorded and assessed in this analysis. Data were inputted into the statistical software of STATA. The studies were weighted by the inverse of the variance and merged in a random-effects model. Results: The systematic review process yielded seven eligible studies including 121 patients with CRAO who received the intravenous rt-PA treatment. 62 patients showed improvement in VA (52.0%; 95% CI, 34.0%-70.0%) following rt-PA intravenous thrombolytic therapy. The observed improvement rate in the intravenous rt-PA treatment group was significantly higher than the conservative treatment group (40.4% vs. 13.0%; OR, =5.16; 95% CI, 1.90-14.05). The incidence rate of complications was relatively low (11 out of the 121 patients). Hemorrhage (9/11) was the major reported complication. Mortality was zero. Conclusion: This meta-analysis indicated that intravenous rt-PA thrombolysis could be an effective and safe strategy for the management of CRAO. However, a more detailed large-scale clinical trial is warranted to strengthen the evidence-based therapeutic guidance.
Evaluation of the national surveillance of Legionnaires’ disease in Norway, 2008-2017
Authors: Wolff Cecilia , Lange Heidi , Feruglio Siri , Vold Line , MacDonald Emily
Published: November 2019

Background In Norway, Legionnaires’ disease is reportable upon clinical suspicion to public health authorities and mandatorily notifiable through the Norwegian surveillance system for communicable diseases (MSIS) for both clinicians and laboratories. In the summer of 2017, several European countries reported high notification rates for Legionnaires’ disease, which was not observed in Norway. We evaluated MSIS to assess if it meets its objectives of detecting cases and trends in incidence of Legionnaires’ disease.Methods We retrieved MSIS data from 2008 to 2017 and calculated timeliness as days from sampling to notification, and internal completeness for key variables as the proportion of observations with a value. Where possible, we assessed internal validity on the presence of a plausible value. To estimate external completeness and validity we linked MSIS with hospital reimbursement claims in the Norwegian Patient Registry. To assess acceptability and representativeness, we surveyed doctors in 39 hospitals on their units’ diagnostic and notification procedures, and their use of MSIS.Results There were 438 notified cases. Internal completeness and internal validity were high for key variables (≥95%). The median delay from sampling to notification was 4 days. There were 73 patients in MSIS only, 70 in the Norwegian Patient Registry only, and 351 in both registers. The external completeness of MSIS was 83% (95% CI 80-86%). For external validity, the positive predictive value of MSIS was 83% (95% CI 79-86%). Forty-seven respondents from 28 hospitals described testing procedures. These were inconsistent: 29 (62%) reported no systematic application of criteria for requesting legionella testing. Eighteen (38%) reported testing all patients with suspected pneumonia and a travel history. Thirty-one (66%) found the notification criteria clear.Conclusions Our results suggest that the surveillance in MSIS can detect incidence changes for Legionnaires’ disease over time, by place and person, but likely does not detect every case diagnosed in Norway. We recommend wider investigation of diagnostic procedures in order to improve representativeness and awareness of MSIS notification criteria among clinicians in order to improve acceptability of the surveillance. We also recommend a more comprehensive assessment of whether patients only registered in the Norwegian Patient Registry were true Legionnaires’ disease cases.
Advocating an attack against severe malaria: a cost-effectiveness analysis
Authors: Greenhalgh Scott , Chandwani Veda
Published: November 2019

Background Recently a study found that the gut microbiota, Lactobacillus and Bifidobacterium, have the ability to modulate the severity of malaria. The modulation of the severity of malaria is not however, the typical focal point of most widespread interventions. Thus, an essential element of information required before serious consideration of any intervention that targets reducing severe malaria incidence is a prediction of the health benefits and costs required to be cost-effective.Methods Here, we developed a mathematical model of malaria transmission to evaluate an intervention that targets reducing severe malaria incidence. We consider intervention scenarios of a 2-, 7-, and 14-fold reduction in severe malaria incidence, based on the potential reduction in severe malaria incidence caused by gut microbiota, under entomological inoculation rates occurring in 41 countries in sub-Saharan Africa. For each intervention scenario, disability-adjusted life years averted and incremental cost-effectiveness ratios were estimated using country specific data, including the reported proportions of severe malaria incidence in healthcare settings.Results Our results show that an intervention that targets reducing severe malaria incidence with annual costs between $23.65 to $30.26 USD per person and causes a 14-fold reduction in severe malaria incidence would be cost-effective in 15-19 countries and very cost-effective in 9-14 countries respectively. Furthermore, if model predictions are based on the distribution of gut microbiota through a freeze-dried yogurt that cost $0.20 per serving, a 2- to 14-fold reduction in severe malaria incidence would be cost-effective in 29 countries and very cost-effective in 25 countries.Conclusion Our findings indicate interventions that target severe malaria can be cost-effective, in conjunction with standard interventions, for reducing the health burden and costs attributed to malaria. While our results illustrate a stronger cost-effectiveness for greater reductions, they consistently show that even a limited reduction in severe malaria provides substantial health benefits, and could be economically viable. Therefore, we suggest that interventions that target severe malaria are worthy of consideration, and merit further empirical and clinical investigation.
­­Lyme borreliosis in Finland: A register-based linkage study
Authors: Feuth Eeva , Virtanen Mikko , Helve Otto , Hytönen Jukka , Sane Jussi
Published: November 2019

Background: In Finland, the routine surveillance of Lyme borreliosis (LB) is laboratory-based. In addition, we have well established national health care registers where countrywide data from patient visits in public health care units are collected. In our previous study based on these registers, we reported an increasing incidence of both microbiologically confirmed and clinically diagnosed LB cases in Finland during the past years. Here, we evaluated our register data, refined LB incidence estimates provided in our previous study, and evaluated treatment practices considering LB in the primary health care. Methods: Three national health care registers were used. The Register for Primary Health Care Visits (Avohilmo) and the National Hospital Discharge Register (Hilmo) collect physician-recorded data from the outpatient and inpatient health care visits, respectively, whereas the National Infectious Diseases Register (NIDR) represents positive findings in LB diagnostics notified electronically by microbiological laboratories. We used a personal identification number in register-linkage to identify LB cases on an individual level in the study year 2014. In addition, antibiotic purchase data was retrieved from the Finnish Social Insurance Institution in order to evaluate the LB treatment practices in the primary health care in Finland.Results: Avohilmo was found to be useful in monitoring clinically diagnosed LB (i.e. EM infections), whereas Hilmo did not add much value next to existing laboratory-based surveillance of disseminated LB. However, Hilmo gave valuable information about uncertainties related to physician-based surveillance of disseminated LB and the total annual number of EM infections in our country. Antibiotic purchases associated with the LB-related outpatient visits in the primary health care indicated a good compliance with the recommended treatment guidelines. Conclusions: In 2018, Avohilmo was introduced in the routine surveillance of LB in Finland next to laboratory-based surveillance of disseminated LB.
Food insecurity during pregnancy in a maternal-infant cohort in Brazilian Western Amazon
Authors: Ramalho Alanderson Alves , Holanda Cibely Machado , Martins Fernanda Andrade , Rodrigues Bárbara Teles Cameli , Andrade Andréia Moreira , Koifman Rosalina Jorge
Published: November 2019

Background The aim of this study was to determine the prevalence and analyze the factors associated with food insecurity during gestation in a maternal-infant cohort in Rio Branco, Acre, Brazilian Western Amazon.Methods A population-based cross-sectional study was conducted with parturients from a maternal-infant cohort in Rio Branco, located in the western Brazilian Amazon. The dependent variable food insecurity was obtained through the Brazilian Scale of Food Insecurity, and associated factors were identified through multiple logistic regression.Results The prevalence of food insecurity in pregnancy was of 34.8% (IC95% = 32.2% - 37.5%). Regarding severity, the prevalence of mild food insecurity was 24.6% (95% CI = 22.3% - 27.0%), moderate food insecurity was 4.8% (95% CI = 3.6% - 6.0%), and severe food insecurity was 5.4% (95% CI = 4.3% - 6.8%). In the final multiple model, the factors directly associated with food insecurity were the presence of open sewage in the peridomestic environment (OR = 1.64; 95% CI: 1.21 - 2.22); belonging to economic classes C, D and E (OR = 1.99; 95% CI: 1.35 - 2.94); being an income transfer program beneficiary (OR = 1.65; 95% CI: 1.18 - 2.30), while the factors inversely associated with FI were schooling equal to or greater than 8 years (OR = 0.66; 95% CI: 0.49 - 0.90); having a partner (OR = 0.56; 95% CI: 0.39 - 0.79); primigestation (OR = 0.59; 95% CI: 0.44 - 0.78) and regular consumption of fruits and vegetables during pregnancy (OR = 0.63, 95% CI: 0.45 - 0.88).Conclusions Despite the existence of income transfer programs, regular consumption of fruits and vegetables is still relatively low and was associated with food insecurity in pregnant women. These findings reinforce the need for the ratification of actions aimed at the domestic economy in the income transfer programs and the development of actions of food and nutritional education in the gestational period.
Rapid shifts in the age-specific burden of malaria following successful control interventions in four regions of Uganda
Authors: Kigozi Simon P. , Kigozi Ruth N. , Epstein Adrienne , Mpimbaza Arthur , Sserwanga Asadu , Yeka Adoke , Nankabirwa Joaniter I. , Halliday Katherine , Pullan Rachel L , Rutazaama Damian , Sebuguzi Catherine M , Opigo Jimmy , Kamya Moses R , Staedke Sarah G , Dorsey Grant , Greenhouse Bryan , Rodriguez-Barraquer Isabel
Published: November 2019

Background: Malaria control using long-lasting insecticidal nets (LLINs) and indoor residual spraying of insecticide (IRS) has been associated with reduced transmission throughout Africa. However, the impact of transmission reduction on the age distribution of malaria cases remains unclear. Methods: Over a 10-year period (January, 2009 to July, 2018), outpatient surveillance data from four health facilities in Uganda were used to estimate the impact of control interventions on temporal changes in the age distribution of malaria cases using multinomial regression. Interventions included mass distribution of LLINs at all sites and IRS at two sites. Results: Overall, 896,550 patient visits were included in the study; 211,632 aged <5 years, 171,166 aged 5-15 years, and 513,752 >15 years. Over time, the age distribution of patients not suspected of malaria and those malaria negative either declined or remained the same across all sites. In contrast, the age distribution of suspected and confirmed malaria cases increased across all four sites for. In the two LLINs-only sites, the proportion of malaria cases in <5 years decreased from 31% to 16% and 35% to 25%, respectively. In the two sites receiving LLINs plus IRS, these proportions decreased from 58% to 30% and 64% to 47%, respectively. Similarly, in the LLINs-only sites, the proportion of malaria cases >15 years of age increased from 40% to 61% and 29% to 39%, respectively. In the sites receiving LLINs plus IRS, these proportions increased from 19% to 44% and 18% to 31%, respectively. Discussion: These findings demonstrate a shift in the burden of malaria from younger to older individuals following implementation of successful control interventions, which has important implications for malaria prevention, surveillance, case management and control strategies.
Multivariate joint modeling to identify markers of growth and lung function decline that predict cystic fibrosis pulmonary exacerbation onset
Authors: Andrinopoulou Eleni-Rosalina , Clancy John Paul , Szczesniak Rhonda
Published: November 2019

Background: Attenuated decreases in lung function can signal the onset of acute respiratory events known as pulmonary exacerbation (PEs) in children and adolescents with cystic fibrosis (CF). Univariate joint modeling facilitates dynamic risk prediction of PE onset and accounts for measurement error of the lung function marker. However, CF is a multi-system disease and the extent to which simultaneously modeling growth and nutrition markers improves PE predictive accuracy is unknown. Furthermore, it is unclear which routinely collected clinical indicators of growth and nutrition in early life predict PE onset in CF. Methods: Using a longitudinal cohort of 17,100 patients aged 6-20 years (US Cystic Fibrosis Foundation Patient Registry; 2003-2015), we fit a univariate joint model of lung-function decline and PE onset and contrasted its predictive performance with a class of multivariate joint models that included combinations of growth markers as additional submodels. Outcomes were longitudinal lung function (forced expiratory volume in 1 s of % predicted), percentile measures of body mass index, weight-for-age and height-for-age and PE onset. Relevant demographic/clinical covariates were included in each submodel. We implemented a univariate joint model of lung function and time-to-PE and four multivariate joint models including growth outcomes. Results: All five joint models showed that declining lung function corresponded to slightly increased risk of PE onset (hazard ratio from univariate joint model: 0.97, P < 0.0001), and all had reasonable predictive accuracy (cross-validated area under the receiver-operator characteristic curve > 0.70). None of the growth markers alongside lung function as outcomes in multivariate joint modeling appeared to have an association with hazard of PE. Jointly modeling only lung function and PE onset yielded the most accurate (area under the receiver-operator characteristic curve = 0.75) and precise (narrowest interquartile range) predictions. Dynamic predictions were accurate across forecast horizons (0.5, 1 and 2 years) and precision improved with age. Conclusions: Including growth markers via multivariate joint models did not yield gains in prediction performance, compared to a univariate joint model with lung function. However, the joint-modeling approach itself may be useful for monitoring CF disease progression by providing a means of dynamic risk prediction.
Functional versus functional and anatomical criteria-guided ranibizumab treatment in patients with neovascular age-related macular degeneration – results from the randomized, phase IIIb OCTAVE study
Authors: Staurenghi Giovanni , Garweg Justus G. , Gerendas Bianca S. , Macfadden Wayne , Gekkiev Boris , Margaron Philippe , Dunger-Baldauf Cornelia , Kolář Petr
Published: November 2019

Background: To evaluate the efficacy and safety of two individualized ranibizumab retreatment schemes in neovascular age-related macular degeneration. Methods: Patients (N=671) were randomized (1:1) to receive three initial monthly ranibizumab 0.5 mg injections, then retreatment guided by either best-corrected visual acuity (BCVA) loss (Group I) or BCVA loss and/or signs of disease activity on optical coherence tomography (OCT; Group II). The study was terminated prematurely and the decision to discontinue the study was made by the sponsor. Efficacy analyses were performed on patients who completed 12 months of the originally planned 24-month study. Safety analyses are presented for all safety analyzable patients. Results: Of 671 randomized patients, 305 completed 12 months of the study. For the 12-month completers, baseline mean (standard deviation) BCVA and reading-center evaluated central subfield thickness (CSFT) were comparable [Group I: 60.9 (13.10) letters and 517.7(201.79) µm; Group II: 60.2 (12.21) letters and 515.3 (198.37) µm]. The change from baseline at Month 12 in BCVA was 6.7 (13.48) letters in Group I and 8.3 (13.53) letters in Group II and the change in CSFT was −161.3 (163.48) µm and −175.3 (170.45) µm, respectively. The mean number of ranibizumab injections was 8.2 in Group I and 8.4 in Group II. Conclusion: Ranibizumab treatment resulted in visual and anatomic gains at 12 months for both retreatment strategies, with a trend in favor of OCT-guided vs BCVA loss guided retreatment. No new safety signals were seen. Trial registration: www.ClinicalTrials.gov (NCT01780935). Registered 31January 2013 Keywords: Best-corrected visual acuity, neovascular age-related macular degeneration, optical coherence tomography, ranibizumab, retreatment criteria