HIV MDR is still a relevant issue despite its dramatic drop over the years

2020 ◽  
Vol 75 (5) ◽  
pp. 1301-1310 ◽  
Author(s):  
D Armenia ◽  
D Di Carlo ◽  
P Flandre ◽  
Y Bouba ◽  
V Borghi ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Cox Regression ◽  
Integrase Inhibitor ◽  
Cox Regression Analysis ◽  
Virological Success ◽  
Susceptibility Score ◽  
Inhibitor Resistance ◽  
Lower Hazard ◽  
Hiv 1

Abstract Objectives To evaluate the prevalence and therapeutic relevance of drug resistance among isolates from ART-experienced HIV-1-infected patients over the past two decades in Italy. Methods Dynamics of resistance to one, two and three or more antiretroviral classes were evaluated from 1999–2018. Virological success (VS) after the latest therapy switch was evaluated according to cumulative class resistance and cumulative genotypic susceptibility score (Stanford HIV_DB algorithm). Results Among 13 663 isolates (from 6739 patients), resistance to at least one drug class decreased sharply from 1999 to 2010 (≤2001, 84.6%; 2010, 43.6%; P < 0.001), then remained relatively constant at ∼40% during 2010–18, with the proportion of resistance to three or more classes also stable (∼5%). After 2008, integrase inhibitor resistance slightly increased from 5.6% to 9.7% in 2018 and contributed to resistance, particularly in isolates with resistance to three or more classes (one class, 8.4%; two classes, 15.3%; three or more classes, 34.7%, P < 0.001). Among 1827 failing patients with an available follow-up, by 1 year after genotype-guided therapy start the probability of VS was 87.6%. Patients with cumulative resistance to three or more classes and receiving a poorly active regimen showed the lowest probability (62.6%) of VS (P < 0.001) compared with all other patients (≥81.8%). By Cox regression analysis, cumulative MDR and receiving poorly active antiretroviral regimens were associated with a lower hazard of VS compared with those without resistance. Conclusions A dramatic drop of HIV-1 drug resistance at failure has been achieved over the last two decades in Italy; resistance to three or more classes is low but present among currently failing patients. Its management still requires a rational and careful diagnostic and therapeutic approach.

scholarly journals Characterizing HIV-1 Genetic Subtypes and Drug Resistance Mutations among Children, Adolescents and Pregnant Women in Sierra Leone

Genes ◽  
2021 ◽  
Vol 12 (9) ◽  
pp. 1314
Author(s):  
George A. Yendewa ◽  
Sulaiman Lakoh ◽  
Sahr A. Yendewa ◽  
Khadijah Bangura ◽  
Andrés Tabernilla ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Pregnant Women ◽  
Sierra Leone ◽  
Integrase Inhibitor ◽  
Sub Saharan Africa ◽  
Success Rates ◽  
Resistance Mutations ◽  
Cross Sectional ◽  
Susceptibility Score ◽  
Hiv 1

Human immunodeficiency virus (HIV) drug resistance (HIVDR) is widespread in sub-Saharan Africa. Children and pregnant women are particularly vulnerable, and laboratory testing capacity remains limited. We, therefore, used a cross-sectional design and convenience sampling to characterize HIV subtypes and resistance-associated mutations (RAMs) in these groups in Sierra Leone. In total, 96 children (age 2–9 years, 100% ART-experienced), 47 adolescents (age 10–18 years, 100% ART-experienced), and 54 pregnant women (>18 years, 72% ART-experienced) were enrolled. Median treatment durations were 36, 84, and 3 months, respectively, while the sequencing success rates were 45%, 70%, and 59%, respectively, among children, adolescents, and pregnant women. Overall, the predominant HIV-1 subtype was CRF02_AG (87.9%, 95/108), with minority variants constituting 12%. Among children and adolescents, the most common RAMs were M184V (76.6%, n = 49/64), K103N (45.3%, n = 29/64), Y181C/V/I (28.1%, n = 18/64), T215F/Y (25.0%, n = 16/64), and V108I (18.8%, n = 12/64). Among pregnant women, the most frequent RAMs were K103N (20.6%, n = 7/34), M184V (11.8%, n = 4/34), Y181C/V/I (5.9%, n = 2/34), P225H (8.8%, n = 3/34), and K219N/E/Q/R (5.9%, n = 2/34). Protease and integrase inhibitor-RAMs were relatively few or absent. Based on the genotype susceptibility score distributions, 73%, 88%, and 14% of children, adolescents, and pregnant women, respectively, were not susceptible to all three drug components of the WHO preferred first-line regimens per 2018 guidelines. These findings suggest that routine HIVDR surveillance and access to better ART choices may improve treatment outcomes in Sierra Leone.

Does Hospitalization Predict the Disease Course in Ulcerative Colitis? Prevalence and Predictors of Hospitalization and Re- Hospitalization in Ulcerative Colitis in a Population-based Inception Cohort (2000-2012)

2015 ◽  
Vol 24 (3) ◽  
pp. 287-292 ◽  
Author(s):  
Petra A. Golovics ◽  
Laszlo Lakatos ◽  
Michael D. Mandel ◽  
Barbara D. Lovasz ◽  
Zsuzsanna Vegh ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Cox Regression ◽  
Diagnostic Procedures ◽  
Population Based ◽  
Disease Course ◽  
Inception Cohort ◽  
Disease Extent ◽  
Cox Regression Analysis ◽  
Hospitalization Rates

Background & Aims: Limited data are available on the hospitalization rates in population-based studies. Since this is a very important outcome measure, the aim of this study was to analyze prospectively if early hospitalization is associated with the later disease course as well as to determine the prevalence and predictors of hospitalization and re-hospitalization in the population-based ulcerative colitis (UC) inception cohort in the Veszprem province database between 2000 and 2012. Methods: Data of 347 incident UC patients diagnosed between January 1, 2000 and December 31, 2010 were analyzed (M/F: 200/147, median age at diagnosis: 36, IQR: 26-50 years, follow-up duration: 7, IQR 4-10 years). Both in- and outpatient records were collected and comprehensively reviewed. Results: Probabilities of first UC-related hospitalization were 28.6%, 53.7% and 66.2% and of first re-hospitalization were 23.7%, 55.8% and 74.6% after 1-, 5- and 10- years of follow-up, respectively. Main UC-related causes for first hospitalization were diagnostic procedures (26.7%), disease activity (22.4%) or UC-related surgery (4.8%), but a significant percentage was unrelated to IBD (44.8%). In Kaplan-Meier and Cox-regression analysis disease extent at diagnosis (HR extensive: 1.79, p=0.02) or at last follow-up (HR: 1.56, p=0.001), need for steroids (HR: 1.98, p<0.001), azathioprine (HR: 1.55, p=0.038) and anti-TNF (HR: 2.28, p<0.001) were associated with the risk of UC-related hospitalization. Early hospitalization was not associated with a specific disease phenotype or outcome; however, 46.2% of all colectomies were performed in the year of diagnosis. Conclusion: Hospitalization and re-hospitalization rates were relatively high in this population-based UC cohort. Early hospitalization was not predictive for the later disease course.

Red Blood Cell Indices in Relation to Post-stroke Psychiatric Disorders: A Longitudinal Study in a Follow-up Stroke Clinic

2020 ◽  
Vol 17 (3) ◽  
pp. 218-223
Author(s):  
Haichao Wang ◽  
Li Gong ◽  
Xiaomei Xia ◽  
Qiong Dong ◽  
Aiping Jin ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Ischemic Stroke ◽  
Blood Cell ◽  
Cox Regression ◽  
Depression And Anxiety ◽  
Cox Regression Analysis ◽  
Post Stroke ◽  
Rbc Indices ◽  
Post Stroke Depression

Background: Depression and anxiety after stroke are common conditions that are likely to be neglected. Abnormal red blood cell (RBC) indices may be associated with neuropsychiatric disorders. However, the association of RBC indices with post-stroke depression (PSD) and poststroke anxiety (PSA) has not been sufficiently investigated. Methods: We aimed to investigate the trajectory of post-stroke depression and anxiety in our follow- up stroke clinic at 1, 3, and 6 months, and the association of RBC indices with these. One hundred and sixty-two patients with a new diagnosis of ischemic stroke were followed up at 1, 3, and 6 months, and underwent Patient Health Questionnaire-9 (PHQ-9) and the general anxiety disorder 7-item (GAD-7) questionnaire for evaluation of depression and anxiety, respectively. First, we used Kaplan-Meier analysis to investigate the accumulated incidences of post-stroke depression and post-stroke anxiety. Next, to explore the association of RBC indices with psychiatric disorders after an ischemic stroke attack, we adjusted for demographic and vascular risk factors using multivariate Cox regression analysis. Results: Of the 162 patients with new-onset of ischemic stroke, we found the accumulated incidence rates of PSD (1.2%, 17.9%, and 35.8%) and PSA (1.2%, 13.6%, and 15.4%) at 1, 3, and 6 months, respectively. The incident PSD and PSA increased 3 months after a stroke attack. Multivariate Cox regression analysis indicated independent positive associations between PSD risk and higher mean corpuscular volume (MCV) (OR=1.42, 95% CI=1.16-1.76), older age (OR=2.63, 95% CI=1.16-5.93), and a negative relationship between male sex (OR=0.95, 95% CI=0.91-0.99) and PSA. Conclusion: The risks of PSD and PSA increased substantially 3 months beyond stroke onset. Of the RBC indices, higher MCV, showed an independent positive association with PSD.

scholarly journals P-Cresyl Sulfate Is a Valuable Predictor of Clinical Outcomes in Pre-ESRD Patients

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Cheng-Jui Lin ◽  
Chi-Feng Pan ◽  
Chih-Kuang Chuang ◽  
Fang-Ju Sun ◽  
Duen-Jen Wang ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Cardiovascular Event ◽  
Cox Regression ◽  
Medical Center ◽  
Serum Biochemistry ◽  
Cox Regression Analysis ◽  
Kaplan Meier ◽  
Valuable Marker ◽  
Valuable Predictor

Background/Aims. Previous studies have reported p-cresyl sulfate (PCS) was related to endothelial dysfunction and adverse clinical effect. We investigate the adverse effects of PCS on clinical outcomes in a chronic kidney disease (CKD) cohort study.Methods. 72 predialysis patients were enrolled from a single medical center. Serum biochemistry data and PCS were measured. The clinical outcomes including cardiovascular event, all-cause mortality, and dialysis event were recorded during a 3-year follow-up.Results. After adjusting other independent variables, multivariate Cox regression analysis showed age (HR: 1.12,P=0.01), cardiovascular disease history (HR: 6.28,P=0.02), and PCS (HR: 1.12,P=0.02) were independently associated with cardiovascular event; age (HR: 0.91,P<0.01), serum albumin (HR: 0.03,P<0.01), and PCS level (HR: 1.17,P<0.01) reached significant correlation with dialysis event. Kaplan-Meier analysis revealed that patients with higher serum p-cresyl sulfate (>6 mg/L) were significantly associated with cardiovascular and dialysis event (log rankP=0.03, log rankP<0.01, resp.).Conclusion. Our study shows serum PCS could be a valuable marker in predicting cardiovascular event and renal function progression in CKD patients without dialysis.

Predicting long-term cardiovascular outcomes of patients with acute myocardial infarction using soluble ST2

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Mustafa Umut Somuncu ◽  
Belma Kalayci ◽  
Ahmet Avci ◽  
Tunahan Akgun ◽  
Huseyin Karakurt ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Cox Regression ◽  
High Serum ◽  
Major Adverse Cardiovascular Events ◽  
Lower Systolic Blood Pressure ◽  
Cox Regression Analysis ◽  
Killip Class ◽  
Target Vessel Revascularization

AbstractBackgroundThe increase in soluble suppression of tumorigenicity 2 (sST2) both in the diagnosis and prognosis of heart failure is well established; however, existing data regarding sST2 values as the prognostic marker after myocardial infarction (MI) are limited and have been conflicting. This study aimed to assess the clinical significance of sST2 in predicting 1-year adverse cardiovascular (CV) events in MI patients.Materials and methodsIn this prospective study, 380 MI patients were included. Participants were grouped into low sST2 (n = 264, mean age: 60.0 ± 12.1 years) and high sST2 groups (n = 116, mean age: 60.5 ± 11.6 years), and all study populations were followed up for major adverse cardiovascular events (MACE) which are composed of CV mortality, target vessel revascularization (TVR), non-fatal reinfarction, stroke and heart failure.ResultsDuring a 12-month follow-up, 68 (17.8%) patients had MACE. CV mortality and heart failure were significantly higher in the high sST2 group compared to the low sST2 group (15.5% vs. 4.9%, p = 0.001 and 8.6% vs. 3.4% p = 0.032, respectively). Multivariate Cox regression analysis concluded that high serum sST2 independently predicted 1-year CV mortality [hazard ratio (HR) 2.263, 95% confidence interval (CI) 1.124–4.557, p = 0.022)]. Besides, older age, Killip class >1, left anterior descending (LAD) as the culprit artery and lower systolic blood pressure were the other independent risk factors for 1-year CV mortality.ConclusionsHigh sST2 levels are an important predictor of MACE, including CV mortality and heart failure in a 1-year follow-up period in MI patients.

Long-Term Clinical Outcome in Elderly Patients Undergoing Mitral Valve Repair

2020 ◽  
Author(s):  
Julia Götte ◽  
Armin Zittermann ◽  
Kavous Hakim-Meibodi ◽  
Masatoshi Hata ◽  
Rene Schramm ◽  
...  
Keyword(s):  
Mitral Valve ◽  
General Population ◽  
Elderly Patients ◽  
Cox Regression ◽  
Functional Class ◽  
Tricuspid Valve Repair ◽  
Valve Repair ◽  
Cox Regression Analysis

Abstract Background Long-term data on patients over 75 years undergoing mitral valve (MV) repair are scarce. At our high-volume institution, we, therefore, aimed to evaluate mortality, stroke risk, and reoperation rates in these patients. Methods We investigated clinical outcomes in 372 patients undergoing MV repair with (n = 115) or without (n = 257) tricuspid valve repair. The primary endpoint was the probability of survival up to a maximum follow-up of 9 years. Secondary clinical endpoints were stroke and reoperation of the MV during follow-up. Univariate and multivariable Cox regression analysis was performed to assess independent predictors of mortality. Mortality was also compared with the age- and sex-adjusted general population. Results During a median follow-up period of 37 months (range: 0.1–108 months), 90 patients died. The following parameters were independently associated with mortality: double valve repair (hazard ratio, confidence interval [HR, 95% CI]: 2.15, 1.37–3.36), advanced age (HR: 1.07, CI: 1.01–1.14 per year), diabetes (HR: 1.97, CI: 1.13–3.43), preoperative New York Heart Association (NYHA) functional class (HR: 1.41, CI: 1.01–1.97 per class), and operative creatininemax levels (HR: 1.32, CI: 1.13–1.55 per mg/dL). The risk of stroke in the isolated MV and double valve repair groups at postoperative year 5 was 5.0 and 4.1%, respectively (p = 0.65). The corresponding values for the risk of reoperation were 4.0 and 7.0%, respectively (p = 0.36). Nine-year survival was comparable with the general population (53.2 vs. 53.1%). Conclusion Various independent risk factors for mortality in elderly MV repair patients could be identified, but overall survival rates were similar to those of the general population. Consequently, our data indicates that repairing the MV in elderly patients represents a suitable and safe surgical approach.

scholarly journals The Role of Hydraulic Silicate Cements on Long-Term Properties and Biocompatibility of Partial Pulpotomy in Permanent Teeth

Materials ◽  
2021 ◽  
Vol 14 (2) ◽  
pp. 305
Author(s):  
Chung-Min Kang ◽  
Saemi Seong ◽  
Je Seon Song ◽  
Yooseok Shin
Keyword(s):  
Regression Analysis ◽  
Cox Regression ◽  
Antimicrobial Properties ◽  
Permanent Teeth ◽  
Success Rates ◽  
Pulp Tissue ◽  
Cox Regression Analysis ◽  
Clinical Variables

The use of hydraulic silicate cements (HSCs) for vital pulp therapy has been found to release calcium and hydroxyl ions promoting pulp tissue healing and mineralized tissue formation. The present study investigated whether HSCs such as mineral trioxide aggregate (MTA) affect their biological and antimicrobial properties when used as long-term pulp protection materials. The effect of variables on treatment outcomes of three HSCs (ProRoot MTA, OrthoMTA, and RetroMTA) was evaluated clinically and radiographically over a 48–78 month follow-up period. Survival analysis was performed using Kaplan–Meier survival curves. Fisher’s exact test and Cox regression analysis were used to determine hazard ratios of clinical variables. The overall success rate of MTA partial pulpotomy was 89.3%; Cumulative success rates of the three HSCs were not statistically different when analyzed by Cox proportional hazard regression analysis. None of the investigated clinical variables affected success rates significantly. These HSCs showed favorable biocompatibility and antimicrobial properties in partial pulpotomy of permanent teeth in long-term follow-up, with no statistical differences between clinical factors.

scholarly journals GT-Repeat Polymorphism in the HO-1 Gene Promoter Is Associated with Risk of Liver Cancer: A Follow-Up Study from Arseniasis-Endemic Areas in Taiwan

2021 ◽  
Vol 10 (7) ◽  
pp. 1489
Author(s):  
Meei-Maan Wu ◽  
Fang-I Hsieh ◽  
Ling-I Hsu ◽  
Te-Chang Lee ◽  
Hung-Yi Chiou ◽  
...  
Keyword(s):  
Liver Cancer ◽  
Cancer Risk ◽  
Cox Regression ◽  
Therapeutic Potential ◽  
Gene Promoter ◽  
Experimental Models ◽  
Heme Oxygenase 1 ◽  
Cox Regression Analysis ◽  
S Alleles

The induction of heme oxygenase-1 (HO-1) has been shown to have therapeutic potential in experimental models of hepatitis and liver fibrosis, which are closely related to liver cancer. In humans, HO-1 induction is transcriptionally modulated by the length of a GT-repeat [(GT)n] in the promoter region. We aimed to investigate the effect of HO-1 (GT)n variants on liver cancer in a human population. We determined the HO-1 genotype in 1153 study subjects and examined their association with liver cancer risk during a 15.9-year follow-up. Allelic polymorphisms were classified as short [S, <27 (GT)n] or long [L, ≥27 (GT)n]. Newly developed cancer cases were identified through linkage to the National Cancer Registry of Taiwan. Multivariate Cox regression analysis was used to evaluate the effect of the HO-1 (GT)n variants. Alpha-fetoprotein (AFP) and cirrhosis history were also examined. The S/S genotype was found to be significantly associated with liver cancer risk, compared to the L/S and L/L genotypes. The S/S genotype group also had a higher percentage of subjects with abnormal AFP levels than other groups. There were significant percentages of cirrhosis among groups who carried S-alleles. Our findings indicate that short (GT)n variants in the HO-1 gene may confer susceptibility to rather than protection from liver cirrhosis/cancer.

scholarly journals Myocardial Metabolic Response Predicts Chemotherapy Curative Potential on Hodgkin Lymphoma: A Proof-of-Concept Study

Biomedicines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 971
Author(s):  
Cecilia Marini ◽  
Matteo Bauckneht ◽  
Anna Borra ◽  
Rita Lai ◽  
Maria Isabella Donegani ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Cox Regression ◽  
Metabolic Response ◽  
Progression Free Survival ◽  
Disease Relapse ◽  
Cox Regression Analysis ◽  
Normal Tissues ◽  
Pet Ct ◽  
Genome Sharing

Genome sharing between cancer and normal tissues might imply a similar susceptibility to chemotherapy toxicity. The present study aimed to investigate whether curative potential of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) is predicted by the metabolic response of normal tissues in patients with Hodgkin lymphoma (HL). METHODS: According to current guidelines, 86 patients with advanced-stage (IIB-IVB) HL, prospectively enrolled in the HD0607 trial (NCT00795613), underwent 18 F-fluorodeoyglucose PET/CT imaging at diagnosis and, at interim, after two ABVD courses, to decide regimen maintenance or its escalation. In both scans, myocardial FDG uptake was binarized according to its median value. Death and disease relapse were recorded to estimate progression-free survival (PFS) during a follow-up with median duration of 43.8 months (range 6.97–60). RESULTS: Four patients (4.6%) died, while six experienced disease relapse (7%). Complete switch-off of cancer lesions and cardiac lighting predicted a favorable outcome at Kaplan–Mayer analyses. The independent nature and additive predictive value of their risk prediction were confirmed by the multivariate Cox regression analysis. CONCLUSION: Susceptibility of HL lesions to chemotherapy is at least partially determined by factors featuring the host who developed it.

scholarly journals Association between post-balloon angioplasty dissection and primary patency in complex femoropopliteal artery disease: 2-year clinical outcomes of the AcoArt I trial

2021 ◽  
Vol 49 (4) ◽  
pp. 030006052110065
Author(s):  
Hao Ren ◽  
Jie Liu ◽  
Jiwei Zhang ◽  
Baixi Zhuang ◽  
Weiguo Fu ◽  
...  
Keyword(s):  
Balloon Angioplasty ◽  
Cox Regression ◽  
Target Lesion ◽  
Transluminal Angioplasty ◽  
Outcome Data ◽  
Primary Patency ◽  
Cox Regression Analysis ◽  
Femoropopliteal Artery ◽  
Artery Disease

Objective To assess the association between post-balloon angioplasty dissection and the mid-term results of the AcoArt I trial evaluating complex femoropopliteal artery disease. Methods The outcome data for 144 patients from the AcoArt 1 trial were reanalysed. These patients were randomly divided into percutaneous transluminal angioplasty (PTA) and drug-coated balloons (DCB) groups. The primary endpoint was the primary patency (PP) rate and clinically-driven target lesion revascularisation at 24 months. Results After 24 months of follow-up, the PP rate of dissection cases in the PTA group was lower vs non-dissection cases. In patients receiving a bailout stent for dissection, the PP rate in the PTA group was lower vs the DCB group. Cox regression analysis showed that dissection decreased the PP rate; mild dissection reduced the PP rate as follows: 52%, PTA group and 19%, DCB group. With severe dissection, the PP rate reduction was as follows: 75%, PTA group and 73%, DCB group. Conclusions The mid-term follow-up showed that post-balloon angioplasty dissection reduced the PP rate in the PTA group but not in the DCB group. Additionally, in patients receiving a bailout stent for dissection, the DCB group had a better PP rate than the PTA group.

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