scholarly journals Socio-demographic, clinical and health facility-related predictors of delayed HIV diagnosis among patients newly diagnosed with HIV in Northwest Ethiopia: a multilevel analysis

2020 ◽  
Author(s):  
Nurilign Abebe Moges ◽  
Yemane Berhane ◽  
Joshua Odunayo AKINYEMI ◽  
Micheal A. Okunlola ◽  
Olubukola Adeponle Adesina
Keyword(s):  
Health Facility ◽  
Advanced Disease ◽  
Northwest Ethiopia ◽  
Disease Stage ◽  
Newly Diagnosed ◽  
Hiv Diagnosis ◽  
Factors Associated ◽  
Multilevel Logistic Regression Analysis ◽  
Advanced Disease Stage ◽  
Facility Level

Abstract Background Ethiopia recently implemented the ‘test and treat’ strategy for all HIV-infected individuals receiving a diagnosis at the health facility level. However, the impact of this policy in terms of timely HIV diagnosis and factors associated with it were not evaluated. Therefore, this study aimed to determine the magnitude and predictors of delayed HIV diagnosis among newly diagnosed people living with HIV in the northwest, Ethiopia. Methods In this cross-sectional study, a total of 759 newly diagnosed patients were recruited consecutively. The multistage sampling technique was employed to select health facilities and all newly diagnosed patients were included. Delayed HIV diagnosis was defined when there is an established AIDS-defining clinical condition (WHO clinical stage III or IV), irrespective of CD4 count. Data were entered into Epi-Data version 3.5 and exported to STATA version 14 for further analysis. Taking into account the nested structure of the data, multilevel logistic regression analysis has been employed. Four models containing variables of interest were fitted. Multivariate multilevel logistic regression analysis was performed to estimate the adjusted odds ratios (AOR) at a 95% confidence interval (CI). Results A one-fourth of newly diagnosed HIV patients diagnosed at advanced disease stage. After controlling for other individual and health facility level factors, factors associated with delayed HIV diagnosis were: Patients who had completed secondary school or higher (AOR = 2.08, 95% CI = 1.06, 4.08), patients who presented to health facilities with HIV symptoms (AOR = 5.87, 95% CI = 3.57, 9.62), being non-working functional status (AOR = 4.80, 95% CI = 2.58, 8.92) and HIV diagnosis at hospitals (AOR = 2.16, 95% CI = 1.08, 4.31). Conclusion The magnitude of delayed HIV diagnosis was improved. In addition to individual-level factors, it is important to address health facility-related factors to improve earlier HIV diagnosis. Here, we recommend using both clinical and laboratory characteristics of a patient particularly, baseline CD4 count and viral load to identify patients diagnosed with advanced disease stage. Moreover, public health interventions are important targeted on factors associated with delayed HIV diagnosis.

scholarly journals Loss of cIAP1 in Endothelial Cells Limits Metastatic Extravasation through Tumor-Derived Lymphotoxin Alpha

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 599
Author(s):  
Lazaros Vasilikos ◽  
Kay Hänggi ◽  
Lisanne M. Spilgies ◽  
Samanta Kisele ◽  
Stefanie Rufli ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Tumor Cells ◽  
Advanced Disease ◽  
Disease Stage ◽  
Stromal Compartment ◽  
Tumor Load ◽  
Smac Mimetics ◽  
Advanced Disease Stage ◽  
Lymphotoxin Alpha ◽  
Open Question

In this study, we determined whether Smac mimetics play a role in metastasis, specifically in circulation, tumor extravasation and growth in a metastatic site. Reports suggest inducing the degradation of IAPs through use of Smac mimetics, alters the ability of the tumor cell to metastasize. However, a role for the immune or stromal compartment in affecting the ability of tumor cells to metastasize upon loss of IAPs has not been defined. To address this open question, we utilized syngeneic tumor models in a late-stage model of metastasis. Loss of cIAP1 in the endothelial compartment, rather than depletion of cIAP2 or absence of cIAP1 in the hematopoietic compartment, caused reduction of tumor load in the lung. Our results underline the involvement of the endothelium in hindering tumor cell extravasation upon loss of cIAP1, in contrast to the immune compartment. Endothelial specific depletion of cIAP1 did not lead to cell death but resulted in an unresponsive endothelium barrier to permeability factors causing a decrease in tumor cell extravasation. Surprisingly, lymphotoxin alpha (LTA), and not TNF, secreted by the tumor cells, was critical for the extravasation. Using TCGA, we found high LTA mRNA expression correlated with decreased survival in kidney carcinoma and associated with advanced disease stage. Our data suggest that Smac mimetics, targeting cIAP1/2, reduce metastasis to the lung by inhibiting tumor cell extravasation.

scholarly journals Epidemiological factors associated with recent HIV infection among newly-diagnosed cases in Singapore, 2013–2017

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Li Wei Ang ◽  
Carmen Low ◽  
Chen Seong Wong ◽  
Irving Charles Boudville ◽  
Matthias Paul Han Sim Toh ◽  
...  
Keyword(s):  
Early Diagnosis ◽  
Hiv Infection ◽  
Hiv Transmission ◽  
Risk Groups ◽  
Newly Diagnosed ◽  
Hiv Diagnosis ◽  
Factors Associated ◽  
Epidemiological Factors ◽  
Voluntary Testing ◽  
Recent Hiv Infection

AbstractBackgroundEarly diagnosis is crucial in securing optimal outcomes in the HIV care cascade. Recent HIV infection (RHI) serves as an indicator of early detection in the course of HIV infection. Surveillance of RHI is important in uncovering at-risk groups in which HIV transmission is ongoing. The study objectives are to estimate the proportion of RHI among persons newly-diagnosed in 2013–2017, and to elucidate epidemiological factors associated with RHI in Singapore.MethodsAs part of the National HIV Molecular Surveillance Programme, residual plasma samples of treatment-naïve HIV-1 positive individuals were tested using the biotinylated peptide-capture enzyme immunoassay with a cutoff of normalized optical density ≤ 0.8 for evidence of RHI. A recent infection testing algorithm was applied for the classification of RHI. We identified risk factors associated with RHI using logistic regression analyses.ResultsA total of 701 newly-diagnosed HIV-infected persons were included in the study. The median age at HIV diagnosis was 38 years (interquartile range, 28–51). The majority were men (94.2%), and sexual route was the predominant mode of HIV transmission (98.3%). Overall, 133/701 (19.0, 95% confidence interval [CI] 16.2–22.0%) were classified as RHI. The proportions of RHI in 2015 (31.1%) and 2017 (31.0%) were significantly higher than in 2014 (11.2%). A significantly higher proportion of men having sex with men (23.4, 95% CI 19.6–27.6%) had RHI compared with heterosexual men (11.1, 95% CI 7.6–15.9%). Independent factors associated with RHI were: age 15–24 years (adjusted odds ratio [aOR] 4.18, 95% CI 1.69–10.31) compared with ≥55 years; HIV diagnosis in 2015 (aOR 2.36, 95% CI 1.25–4.46) and 2017 (aOR 2.52, 95% CI 1.32–4.80) compared with 2013–2014; detection via voluntary testing (aOR 1.91, 95% CI 1.07–3.43) compared with medical care; and self-reported history of HIV test(s) prior to diagnosis (aOR 1.72, 95% CI 1.06–2.81).ConclusionAlthough there appears to be an increasing trend towards early diagnosis, persons with RHI remain a minority in Singapore. The strong associations observed between modifiable behaviors (voluntary testing and HIV testing history) and RHI highlight the importance of increasing the accessibility to HIV testing for at-risk groups.

Malignant mesothelioma: prognostic variables in a registry of 180 patients, the Dana-Farber Cancer Institute and Brigham and Women's Hospital experience over two decades, 1965-1985.

1988 ◽  
Vol 6 (1) ◽  
pp. 147-153 ◽  
Author(s):  
K Antman ◽  
R Shemin ◽  
L Ryan ◽  
K Klegar ◽  
R Osteen ◽  
...  
Keyword(s):  
Chest Pain ◽  
Advanced Disease ◽  
Performance Status ◽  
Randomized Study ◽  
Prolonged Survival ◽  
Disease Stage ◽  
Computer Search ◽  
Prognostic Variables ◽  
Dana Farber Cancer Institute ◽  
Advanced Disease Stage

All mesothelioma patients identified by a computer search of pathologic diagnoses at the Dana-Farber Cancer Institute (DFCI) between 1965 and 1985 were the subjects of this analysis. A total of 180 patients were identified, 136 with pleural and 37 with peritoneal mesothelioma. There were five pericardial and two testicular primaries. Of the two decades included in the study, later patients were significantly older, with a more advanced disease stage, and a lower performance status than those accrued early in the study. Factors at diagnosis associated with a significantly prolonged survival for all patients with mesothelioma included a 0 to 1 performance status, absence of chest pain, age less than 50 years, and epithelial histology. Factors at diagnosis associated with prolonged survival for the subset of patients with pleural mesothelioma included epithelial histology, 0 to 1 performance status, the absence of chest pain, an interval of greater than 6 months from onset of symptoms, and treatment with chemotherapy and pleuropneumonectomy. This last result must be interpreted with caution, since this was not a randomized study.

scholarly journals T2-Pseudonormalization and Microstructural Characterization in Advanced Stages of Late-infantile Metachromatic Leukodystrophy

2020 ◽  
Author(s):  
Pascal Martin ◽  
Gisela E. Hagberg ◽  
Thomas Schultz ◽  
Klaus Harzer ◽  
Uwe Klose ◽  
...  
Keyword(s):  
Metachromatic Leukodystrophy ◽  
Advanced Disease ◽  
Magnetization Transfer ◽  
Brain Magnetic Resonance Imaging ◽  
Disease Stage ◽  
Magnetization Transfer Ratio ◽  
Water Fraction ◽  
Mri Protocol ◽  
Advanced Disease Stage ◽  
Multimodal Mri

Abstract Purpose T2-weighted signal hyperintensities in white matter (WM) are a diagnostic finding in brain magnetic resonance imaging (MRI) of patients with metachromatic leukodystrophy (MLD). In our systematic investigation of the evolution of T2-hyperintensities in patients with the late-infantile form, we describe and characterize T2-pseudonormalization in the advanced stage of the natural disease course. Methods The volume of T2-hyperintensities was quantified in 34 MRIs of 27 children with late-infantile MLD (median age 2.25 years, range 0.5–5.2 years). In three children with the most advanced clinical course (age >4 years) and for whom the T2-pseudonormalization was the most pronounced, WM microstructure was investigated using a multimodal MRI protocol, including diffusion-weighted imaging, MR spectroscopy (MRS), myelin water fraction (MWF), magnetization transfer ratio (MTR), T1-mapping and quantitative susceptibility mapping. Results T2-hyperintensities in cerebral WM returned to normal in large areas of 3 patients in the advanced disease stage. Multimodal assessment of WM microstructure in areas with T2-pseudonormalization revealed highly decreased values for NAA, neurite density, isotropic water, mean and radial kurtosis, MWF and MTR, as well as increased radial diffusivity. Conclusion In late-infantile MLD patients, we found T2-pseudonormalization in WM tissue with highly abnormal microstructure characterizing the most advanced disease stage. Pathological hallmarks might be a loss of myelin, but also neuronal loss as well as increased tissue density due to gliosis and accumulated storage material. These results suggest that a multimodal MRI protocol using more specific microstructural parameters than T2-weighted sequences should be used when evaluating the effect of treatment trials in MLD.

Allogeneic Hematopoietic Stem Cell Transplantation for Patients with Myelodysplastic Syndromes 50 Years or Older. A Retrospective Survey from the EBMT.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 520-520 ◽  
Author(s):  
ZiYi Lim ◽  
Ronald Brand ◽  
Anja van Biezen ◽  
Jurgen Finke ◽  
Dietger W. Niederwieser ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Advanced Disease ◽  
Disease Stage ◽  
Hematopoietic Stem ◽  
Donor Type ◽  
Advanced Disease Stage

Abstract Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative treatment for patients with MDS. However, the advanced age of the majority of patients with MDS poses a significant barrier to the success of transplantation. Many of these patients have co-morbidities, or lack a suitable sibling matched donor. While reduced intensity conditioning (RIC) has expanded the scope of allografting to older patients, it remains unclear as to whether it confers an improvement in overall survival in this patient sub-group. Here we report on the results of a retrospective multi-centre analysis of 1385 patients aged 50 years or older with MDS transplanted since 1993. The main variables analysed in this study were donor status (sibling vs unrelated matched), age group (50–60 years vs >60years), disease stage at time of transplantation (early:<5% blasts vs advanced:>5% blasts), type of conditioning regimen (RIC vs standard myeloablative conditioning, SMC), period of transplantation (1993–96, 1997–2000–2001-). There were 1000 matched sibling (72%) and 385 matched unrelated donor transplants (28%). The median age of the cohort was 56 years (range:50–74 years), with 1053 patients (76%) aged 50–60 years and 332 patients (24%) above 60 years. 604 patients(44%) received SMC and 781 patients (56%) received RIC. 189 patients (14%) had RA/RARS, 388 patients (28%) had RAEB, 233 patients(17%) had RAEB-t and 393 patients secondary AML (28%). FAB classification was unavailable for 182 patients (13%). Patients receiving RIC were older (age>60 years: 30% RIC vs 14% SMC, p<0.001), but SMC had a more advanced disease stage at transplant (42% RIC vs 51% SMC). There was no difference in donor type between RIC and SMC (MUD: 28% RIC vs 28% SMC) The estimated cumulative incidence (competing risk model) at 4-years post transplant for TRM decreased from 47%(1993–1996), via 40%(1997–2000) to 35%(2001-); for Relapse Incidence these figures are 29%, 33% and 40% respectively. On multivariate analysis, age >60 years(HR:1.28, 95%CI [1.0–1.6], p=0.04), use of RIC (HR:1.50 95%CI [1.2–1.9], p<0.001) and advanced disease stage at transplantation (HR:1.51, 95%CI [1.2–2.0], p=0.002) were associated with an increased relapse rate; the use of RIC with a lower TRM (HR:0.71, 95%CI [0.57–0.88], p<0.01) and advanced disease stage at transplantation with a higher TRM (HR: 1.4, 95%CI [1.1–1.8], p<0.01) In contrast, donor type did not significantly influence either the 4-year TRM or relapse rates(HR’s 1.12 and 0.94 respectively, both p>0.30). Advanced disease stage at transplantation was the only independent variable associated with an inferior 4-year overall survival(OS)(HR: 1.47, 95%CI [1.2–1.8], p<0.001). In conclusion, disease stage at time of transplantation has an important prognostic impact on outcomes. The use of RIC is associated with higher relapse but lower TRM and comparable OS with SMC in this cohort. While patients aged >60 years had an increased relapse rate, there was no significant difference in OS compared with those aged 50–60 years. The choice of donor did not significantly influence outcomes. Long-term survival can be achieved in a sub-group of older MDS patients, but prospective studies are warranted to improve patient selection and to identify optimal treatment strategies.

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