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Fulltext Comparing the usefulness of the 1997 and 2009 WHO dengue case classification: a systematic literature review

Horstick O, Jaenisch T, Martinez E, Kroeger A, See LL, Farrar J, et al.

Am J Trop Med Hyg, 2014 Sep;91(3):621-34.
PMID: 24957540 DOI: 10.4269/ajtmh.13-0676

The 1997 and 2009 WHO dengue case classifications were compared in a systematic review with 12 eligible studies (4 prospective). Ten expert opinion articles were used for discussion. For the 2009 WHO classification studies show: when determining severe dengue sensitivity ranges between 59-98% (88%/98%: prospective studies), specificity between 41-99% (99%: prospective study) - comparing the 1997 WHO classification: sensitivity 24.8-89.9% (24.8%/74%: prospective studies), specificity: 25%/100% (100%: prospective study). The application of the 2009 WHO classification is easy, however for (non-severe) dengue there may be a risk of monitoring increased case numbers. Warning signs validation studies are needed. For epidemiological/pathogenesis research use of the 2009 WHO classification, opinion papers show that ease of application, increased sensitivity (severe dengue) and international comparability are advantageous; 3 severe dengue criteria (severe plasma leakage, severe bleeding, severe organ manifestation) are useful research endpoints. The 2009 WHO classification has clear advantages for clinical use, use in epidemiology is promising and research use may at least not be a disadvantage.
Fulltext HIV care models during the COVID-19 era

Guaraldi G, Milic J, Martinez E, Kamarulzaman A, Mussini C, Waters L, et al.

Clin Infect Dis, 2020 Dec 19.
PMID: 33340037 DOI: 10.1093/cid/ciaa1864

The COVID-19 pandemic is an unprecedented global challenge that substantially risks reversing the progress in ending HIV. At the same time, it may offer the opportunity for a new era of HIV management. This viewpoint presents the impact of COVID-19 on HIV care, including the Joint United Nations Programme on HIV/AIDS (UNAIDS) "three 90s" targets. It outlines how to enhance a patient-centered care approach, now known as the "fourth 90," by integrating face-to-face patient-physician and telemedicine encounters. It suggests a framework for prevention and treatment of multimorbidity and frailty, to achieve a good health-related quality of life and preserve intrinsic capacity in all people living with HIV.
Impact of Silymarin Supplements on Liver Enzyme Levels: A Systematic Review

Calderon Martinez E, Herrera D, Mogan S, Hameed Z, Jangda AA, Khan TJ, et al.

Cureus, 2023 Oct;15(10):e47608.
PMID: 38021897 DOI: 10.7759/cureus.47608

Silymarin, extracted from milk thistle (Silybum marianum), is esteemed for its antioxidative, anti-inflammatory, and antifibrotic properties, notably within liver-related contexts. Nevertheless, a comprehensive grasp of its effects on liver enzymes remains elusive. This systematic review aims to scrutinize the influence of silymarin supplements on liver enzyme levels, elucidating its potential for hepatoprotection. Following PRISMA 2020 guidelines, we systematically reviewed pertinent studies in PubMed/MEDLINE (Medical Literature Analysis and Retrieval System Online). Our inclusion criteria comprised randomized clinical trials (RCTs) published between 1992 and 2023, accessible in English, with a primary focus on liver enzyme levels. Non-original research, ambiguously defined studies, and those lacking essential data were excluded. Of the 1,707 initially identified articles, 29 RCTs met the inclusion criteria, encompassing 3,846 participants with diverse underlying conditions. Silymarin dosages ranged from 140 mg to 420 mg, administered for various durations. Results revealed that 65.5% of the studies reported reduced liver enzyme levels, 20.7% exhibited no significant change, and 13.8% observed elevated liver enzymes. The systematic review implies a potential advantageous influence of silymarin on liver enzyme levels, indicating its hepatoprotective potential. Nevertheless, outcome disparities may stem from comorbidities, suboptimal doses, and underlying diseases. Notably, silymarin's impact on liver enzymes could be context-dependent, with varying responses among different conditions, with the decrease of liver enzyme levels in patients with non-alcoholic fatty liver disease. Silymarin supplements exhibit potential for hepatoprotection by ameliorating liver enzyme levels across diverse conditions. Further research should ascertain optimal dosages and contexts, accounting for individual patient characteristics and underlying diseases.
Fulltext Severe dengue categories as research endpoints-Results from a prospective observational study in hospitalised dengue patients

Rosenberger KD, Alexander N, Martinez E, Lum LCS, Dempfle CE, Junghanss T, et al.

PLoS Negl Trop Dis, 2020 Mar;14(3):e0008076.
PMID: 32130212 DOI: 10.1371/journal.pntd.0008076

Severe dengue was perceived as one clinical disease entity until the WHO 2009 classification stratified it into severe vascular leakage, severe bleeding, and severe organ dysfunction. The objectives of this study were to investigate the potential use of severe dengue categories as endpoints for intervention research. 271 patients with severe dengue among 1734 confirmed dengue patients were followed prospectively in this hospital-based observational study in Latin America and Asia. We compared the distribution of severe dengue categories according to gender and age (below/above 15y), and determined the relative frequency and the overlap of severe dengue categories in the same patients. In a next step, we extended the analysis to candidate moderate severity categories, based on recently suggested definitions which were adapted for our purposes. Severe vascular leakage occurred in 244 (90%), severe bleeding in 39 (14%), and severe organ dysfunction in 28 (10%) of 271 severe dengue patients. A higher frequency of severe leakage was seen in children or adolescents (<15y) compared to adults. More than 80% of the severe leakage cases, and 30-50% of the cases with severe bleeding or severe organ dysfunction, were defined as severe on the basis of that feature alone. In 136 out of 213 patients with severe leakage alone, neither moderate bleeding manifestation nor hepatic involvement was recorded. On the other hand, moderate leakage manifestations were detected in 4 out of 12 cases that were classified as severe based on bleeding alone. A major proportion of severe dengue patients exhibited clinical manifestations of severe vascular leakage only, which may constitute a useful endpoint for intervention research or pathophysiology studies. Severe bleeding and severe organ manifestation were recorded less frequently and exhibited a higher degree of overlap with severe leakage. Severe bleeding without leakage may be associated with individual predisposition or the presence of comorbidities. More detailed assessments are needed to explore this hypothesis. Candidate moderate disease endpoints were investigated and need to be further validated.
Fulltext Methods and matrices: approaches to identifying miRNAs for nasopharyngeal carcinoma

Plieskatt JL, Rinaldi G, Feng Y, Levine PH, Easley S, Martinez E, et al.

J Transl Med, 2014;12:3.
PMID: 24393330 DOI: 10.1186/1479-5876-12-3

Nasopharyngeal carcinoma (NPC) is a solid tumor of the head and neck. Multimodal therapy is highly effective when NPC is detected early. However, due to the location of the tumor and the absence of clinical signs, early detection is difficult, making a biomarker for the early detection of NPC a priority. The dysregulation of small non-coding RNAs (miRNAs) during carcinogenesis is the focus of much current biomarker research. Herein, we examine several miRNA discovery methods using two sample matrices to identify circulating miRNAs (c-miRNAs) associated with NPC.
Development of the HIV360 international core set of outcome measures for adults living with HIV: A consensus process

Marques-Gomes J, Salt MJ, Pereira-Neto R, Barteldes FS, Gouveia-Barros V, Carvalho A, et al.

HIV Med, 2021 Dec 28.
PMID: 34964226 DOI: 10.1111/hiv.13221

OBJECTIVES: HIV outcomes centre primarily around clinical markers with limited focus on patient-reported outcomes. With a global trend towards capturing the outcomes that matter most to patients, there is agreement that standardizing the definition of value in HIV care is key to their incorporation. This study aims to address the lack of routine, standardized data in HIV care.
METHODS: An international working group (WG) of 37 experts and patients, and a steering group (SG) of 18 experts were convened from 14 countries. The project team (PT) identified outcomes by conducting a literature review, screening 1979 articles and reviewing the full texts of 547 of these articles. Semi-structured interviews and advisory groups were performed with the WG, SG and people living with HIV to add to the list of potentially relevant outcomes. The WG voted via a modified Delphi process - informed by six Zoom calls - to establish a core set of outcomes for use in clinical practice.
RESULTS: From 156 identified outcomes, consensus was reached to include three patient-reported outcomes, four clinician-reported measures and one administratively reported outcome; standardized measures were included. The WG also reached agreement to measure 22 risk-adjustment variables. This outcome set can be applied to any person living with HIV aged > 18 years.
CONCLUSIONS: Adoption of the HIV360 outcome set will enable healthcare providers to record, compare and integrate standardized metrics across treatment sites to drive quality improvement in HIV care.
Fulltext Two truncating variants in FANCC and breast cancer risk

Dörk T, Peterlongo P, Mannermaa A, Bolla MK, Wang Q, Dennis J, et al.

Sci Rep, 2019 08 29;9(1):12524.
PMID: 31467304 DOI: 10.1038/s41598-019-48804-y

Fanconi anemia (FA) is a genetically heterogeneous disorder with 22 disease-causing genes reported to date. In some FA genes, monoallelic mutations have been found to be associated with breast cancer risk, while the risk associations of others remain unknown. The gene for FA type C, FANCC, has been proposed as a breast cancer susceptibility gene based on epidemiological and sequencing studies. We used the Oncoarray project to genotype two truncating FANCC variants (p.R185X and p.R548X) in 64,760 breast cancer cases and 49,793 controls of European descent. FANCC mutations were observed in 25 cases (14 with p.R185X, 11 with p.R548X) and 26 controls (18 with p.R185X, 8 with p.R548X). There was no evidence of an association with the risk of breast cancer, neither overall (odds ratio 0.77, 95%CI 0.44-1.33, p = 0.4) nor by histology, hormone receptor status, age or family history. We conclude that the breast cancer risk association of these two FANCC variants, if any, is much smaller than for BRCA1, BRCA2 or PALB2 mutations. If this applies to all truncating variants in FANCC it would suggest there are differences between FA genes in their roles on breast cancer risk and demonstrates the merit of large consortia for clarifying risk associations of rare variants.