Systemic inflammation and residual viraemia in HIV-positive adults on protease inhibitor monotherapy: a cross-sectional study.

Increased levels of markers of systemic inflammation have been associated with serious non-AIDS events even in patients on fully suppressive antiretroviral therapy. We explored residual viremia and systemic inflammation markers in patients effectively treated with ritonavir-boosted protease inhibitor monotherapy (PImono)

Risky Alcohol Consumption and Associated Health Behaviour Among HIV-Positive and HIV-Negative Patients in a UK Sexual Health and HIV Clinic: A Cross-Sectional Questionnaire Study

Alcohol misuse has been associated with negative consequences among HIV-positive patients. Data on real prevalence of risky alcohol consumption among the HIV-positive population in the UK are lacking. A cross-sectional questionnaire study using standardised validated instruments among HIV-positive (n = 227) and HIV-negative (n = 69) patients was performed. The prevalence of risky alcohol consumption (AUDIT) and associations with depressive symptoms (PHQ-9), problematic drug use (DUDIT), adherence to ART (CASE Adherence Index), sexual behaviour and demographic characteristics were assessed among both patient groups independently. A quarter (25.1%) of HIV-positive patients and 36.1% of HIV-negative patients reported risky alcohol consumption (AUDIT-score ≥ 8). In the multivariable analysis among HIV-positive patients depressive symptoms (p = 0.03) and problematic drug use (p = 0.007) were associated with risky alcohol consumption. Among HIV-negative patients these associations were not present. Risky alcohol consumption among HIV-positive patients is prevalent, and together with depressive symptoms and problematic drug use, may influence HIV-disease progression and patients’ wellbeing

Linear functional organization of the omic embedding space

Motivation: We are increasingly accumulating complex omics data that capture different aspects of cellular functioning. A key challenge is to untangle their complexity and effectively mine them for new biomedical information. To decipher this new information, we introduce algorithms based on network embeddings. Such algorithms represent biological macromolecules as vectors in d-dimensional space, in which topologically similar molecules are embedded close in space and knowledge is extracted directly by vector operations. Recently, it has been shown that neural networks used to obtain vectorial representations (embeddings) are implicitly factorizing a mutual information matrix, called Positive Pointwise Mutual Information (PPMI) matrix. Thus, we propose the use of the PPMI matrix to represent the human protein-protein interaction (PPI) network and also introduce the graphlet degree vector PPMI matrix of the PPI network to capture different topological (structural) similarities of the nodes in the molecular network. Results: We generate the embeddings by decomposing these matrices with Nonnegative Matrix Tri-Factorization. We demonstrate that genes that are embedded close in these spaces have similar biological functions, so we can extract new biomedical knowledge directly by doing linear operations on their embedding vector representations. We exploit this property to predict new genes participating in protein complexes and to identify new cancer-related genes based on the cosine similarities between the vector representations of the genes. We validate 80% of our novel cancer-related gene predictions in the literature and also by patient survival curves that demonstrating that 93.3% of them have a potential clinical relevance as biomarkers of cancer

Fast Neutron And Gamma-ray Detectors For The Csiro Air Cargo Scanner

oS(FNDA2006)074 © Copyright owned by the author(s) under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike Licence

No overall change in the rate of weight gain after switching to an integrase-inhibitor in virologically suppressed adults with HIV

OBJECTIVE: Excessive weight gain has been reported with integrase strand transfer inhibitors (INSTIs). We evaluated weight changes in virologically-suppressed adults with HIV who switched from non-INSTI regimens to raltegravir- or dolutegravir-containing antiretroviral therapy. DESIGN: Retrospective single-centre cohort. METHODS: Adults who switched to raltegravir or dolutegravir before or between January-2015 and October-2017 were identified. Virologically-suppressed, treatment-experienced (≥2 years) individuals, ≥6 months on INSTI, with weight measurements ≤2years pre- and post-switch were included. Our analysis used a random effects model with linear slope pre- and post-INSTI with adjustment for age, gender, ethnicity, pre-switch-regimen (protease inhibitor vs. non-protease inhibitor), and raltegravir vs. dolutegravir use. RESULTS: 378 individuals, 81.2% male, 70.1% white ethnicity, median age of 49 years, median of four weight measurements per participant, and median weight and body mass index (BMI) at switch, of 76.6 kg, and 25.3 kg/m respectively were included. Weight increased by an average of 0.63 kg/year (95% CI 0.17-1.09) pre-switch with no overall change in rate of weight gain post-switch [+0.05 kg/year (-0.61-0.71, p = 0.88)]. In our adjusted model, a transition from minimal weight change to weight gain post-switch was isolated to older individuals though this lacked statistical significance [e.g. +1.59 kg/year (-0.26-3.45) if aged 65 years]. Our findings did not differ by gender, ethnicity, pre-switch regimen, or raltegravir vs. dolutegravir. Similar results were seen for BMI and after adjusting for fixed nucleoside/nucleotide reverse transcriptase inhibitor backbone. CONCLUSION: We found no clear evidence of an overall increase in rate of weight gain following switch to INSTI in virologically-suppressed individuals

Zidovudine/Lamivudine for HIV-1 Infection Contributes to Limb Fat Loss

Lipoatrophy is known to be associated with stavudine as part of the treatment for HIV infection, but it is less clear if this serious side effect is also related to other nucleoside reverse transcriptase inhibitors like zidovudine. We aimed to determine whether zidovudine-sparing first-line antiretroviral therapy would lead to less lipoatrophy and other metabolic changes than zidovudine-containing therapy.Fifty antiretroviral therapy-naïve HIV-1 infected men with an indication to start antiretroviral therapy were included in a randomized single blinded clinical trial. Randomisation was between zidovudine-containing therapy (zidovudine/lamivudine+lopinavir/ritonavir) and zidovudine-sparing therapy (nevirapine+lopinavir/ritonavir). Main outcome measures were body composition assessed by computed tomography and dual-energy X-ray absorptiometry scan and lipid profile before and after 3, 12, 24 months of antiretroviral therapy. In the zidovudine/lamivudine+lopinavir/ritonavir group, from 3 months onward limb fat decreased progressively by 684+/-293 grams (estimated mean+/-standard error of the mean)(p = 0.02) up to 24 months whereas abdominal fat increased, but exclusively in the visceral compartment (+21.9+/-8.1 cm(2), p = 0.008)). In contrast, in the nevirapine+lopinavir/ritonavir group, a generalized increase in fat mass was observed. After 24 months no significant differences in high density lipoprotein and total/high density lipoprotein cholesterol ratio were found between both treatment groups, but total and low density lipoprotein cholesterol levels were higher in the nevirapine+lopinavir/ritonavir group (6.1+/-0.2 versus 5.3+/-0.2 and 3.6+/-0.1 versus 2.8+/-0.1 mmol/l respectively, p<0.05). Virologic response and safety were comparable in both groups.Zidovudine/lamivudine+lopinavir/ritonavir, but not nevirapine+lopinavir/ritonavir in antiretroviral therapy-naïve patients, is associated with lipoatrophy and greater relative intraabdominal lipohypertrophy, suggesting that zidovudine/lamivudine contributes to both these features of lipodystrophy. These findings support to no longer consider zidovudine/lamivudine as one of the preferred possible components of first-line antiretroviral therapy where alternative treatments are available.ClinicalTrials.gov NCT 00122226

Hepatic steatosis in people older and younger than fifty who are living with HIV and HIV-negative controls: A cross-sectional study nested within the POPPY cohort

BACKGROUND: Hepatic steatosis is a major cause of chronic liver disease associated with several negative health outcomes. We compared the prevalence of and factors associated with steatosis in people living with and without HIV. METHODS: Older (>50 years) and younger (50 years) underwent liver transient elastography examination with controlled attenuation parameter (steatosis ≥238 dB/m, moderate/severe steatosis ≥280 dB/m, liver fibrosis ≥7.1 kPa). We compared groups using logistic regression/Chi-squared/Fisher's exact/Kruskal–Wallis tests. RESULTS: In total, 317 participants (109 older people with HIV; 101 younger people with HIV; 107 HIV-negative controls) were predominantly white (86%) and male (76%), and 21% were living with obesity (body mass index ≥30 kg/m2). Most (97%) people with HIV had undetectable HIV RNA. The prevalence of fibrosis was 8.4%, 3.0%, and 6.5% in the three groups, respectively (p = 0.26). Fibrosis was predominately (>65%) mild. The prevalence of steatosis was the same in older people with HIV (66.4%) and controls (66.4%) but lower in younger people with HIV (37.4%; p < 0.001). After adjustment, younger people with HIV were less likely to have steatosis (odds ratio [OR] 0.26; 95% confidence interval [CI] 0.14–0.52) than controls, but male sex (OR 2.45; 95% CI 1.20–4.50) and high waist-to-hip ratio (OR 3.04; 95% CI 1.74–5.33) were associated with an increased odds of steatosis. We found no association between steatosis and HIV-related variables. CONCLUSIONS: The prevalence of hepatic steatosis and fibrosis was similar between older participants regardless of HIV status. Age, sex, and abdominal obesity, but not HIV-related variables, were associated with steatosis. Interventions for controlling obesity should be integrated into routine HIV care

Expect the Unexpected in the Medical Treatment of Heart Failure with Reduced Ejection Fraction: between Scientific Evidence and Clinical Wisdom.

Over the past three decades, pharmacological treatment of heart failure (HF) with reduced ejection fraction (HFrEF) has witnessed a significant progress with the introduction of multiple disease-modifying therapies with a proven benefit on morbidity, mortality and quality of life. Recently, several novel medications (sacubitril/valsartan, sodium-glucose contransporter-2 [SGLT2] inhibitors, vericiguat and omecamtiv mecarbil) have shown to provide further improvement in outcomes in patients already receiving standard therapy for HFrEF. Available evidence suggests that sacubitril/valsartan and SGLT2 inhibitors (dapagliflozin and empagliflozin) are beneficial and well-tolerated in the majority inpatients and could be the mainstay treatment of HFrEF. Another group of medications (vericiguat and omecamtiv mecarbil) has shown promising results in reducing the risk of the composite of HF hospitalisation or cardiovascular mortality in patients with the more severe or advanced HF requiring recent hospitalisation. Therefore, these medications may be considered for the treatment of select group of patients with HFrEF with persisting or worsening symptoms despite optimal treatment. In addition, advances in pharmacological management of comorbidities frequently seen in HFrEF patients (diabetes, iron deficiency/anaemia, hyperkalaemia) provide further opportunities to improve outcomes. Given the increasing complexity of evidence-based therapies for HFrEF, there is a growing need to provide a practical perspective to their use. The purpose of this review is to summarise scientific evidence on the efficacy and safety of new and emerging medical therapies in HFrEF, with a focus on the clinical perspective of their use

Randomized controlled trial of the tolerability and completion of maraviroc compared with Kaletra® in combination with Truvada® for HIV post-exposure prophylaxis (MiPEP Trial).

OBJECTIVES: Post-exposure prophylaxis (PEP) for HIV is often poorly tolerated and not completed. Alternative PEP regimens may improve adherence and completion, aiding HIV prevention. We conducted a randomized controlled trial of a maraviroc-based PEP regimen compared with a standard-of-care regimen using ritonavir-boosted lopinavir. METHODS: Patients meeting criteria for PEP were randomized to tenofovir disoproxil/emtricitabine (200/245 mg) once daily plus ritonavir-boosted lopinavir (Kaletra ® 400/100 mg) or maraviroc 300 mg twice daily. The composite primary endpoint was completion of 28 days of the allocated PEP regimen without grade 3 or 4 clinical or laboratory adverse events (AEs) related to the PEP medication. RESULTS: Two hundred and thirteen individuals were randomized (107 to maraviroc; 106 to Kaletra ® arm). Follow-up rates were high in both groups. There was no difference in the primary endpoint; 70 (71%) in the maraviroc and 64 (65%) in the Kaletra ® arm ( P  =   0.36) completed PEP without grade 3 or 4 AEs. Discontinuation of PEP was the same (18%) in both groups. There were no grade 3 or 4 clinical AEs in either arm, but more grade 1 or 2 clinical AEs in the Kaletra ® arm (91% versus 70%; P  < 0.001). Antidiarrhoeal medication use was higher in the Kaletra ® arm (67% versus 25%; P  < 0.001). There were no HIV seroconversions in the study period. CONCLUSIONS: The completion rate in the absence of grade 3 or 4 AEs was similar with both regimens. Maraviroc-based PEP was better tolerated, supporting its use as an option for non-occupational PEP

Fabrication, workflow and delivery of reconstruction: Summary and consensus statements of group 4. The 6th EAO Consensus Conference 2021.

Objectives: To report assessments of four systematic reviews (SRs) on (i) clinical outcomes of all-ceramic implant-supported crowns (iSCs), (ii) production time, effectiveness, and costs of computer-assisted manufacturing (CAM), (iii) computer-assisted implant planning and surgery (CAIPS) time and costs, and (iv) patient-reported outcome measures (PROMS). Material and methods: An author group consisting of experienced clinicians and content experts discussed and evaluated the SRs and formulated consensus on the main findings, statements, clinical recommendations, and need for future research. Results: All four SRs were conducted and reported according to PRISMA and detailed comprehensive search strategies in at least three bibliometric databases and hand searching. The search strategies were deemed reproducible. Variation was noted regarding language restrictions and inclusion of grey literature, but the search comprehensiveness appeared persuasive. The SRs included bias risk assessments of the primary studies, and their study methodology impacted the interpretations of the extracted data. Conclusions: (i) There is limited evidence (49 NRCT) showing that veneered and monolithic all-ceramic iSCs have excellent outcomes observed up to 3 years. (ii) There is no evidence evaluating production time and effectiveness comparing subtractive and additive CAM of implant models, abutments and crowns. (iii) There is limited evidence (4 RCT) that CAIPS involves more time and costs when considering the entire workflow and for diagnostics, manufacturing, and insertion of the restoration. Time seems to be the decisive factor for higher costs. (iv) Patients' comfort increases when optical compared to conventional impressions are used for fabricating iSCs and short-span FPDs (2 RCT, 5 NRCT)