Progress in prevention of mother-to-child transmission of HIV infection in Ukraine: results from a birth cohort study

Background: Ukraine was the epicentre of the HIV epidemic in Eastern Europe, which has the most rapidly accelerating HIV epidemic world-wide today; national HIV prevalence is currently estimated at 1.6%. Our objective was to evaluate the uptake and effectiveness of interventions for prevention of mother-to-child transmission (PMTCT) over an eight year period within operational settings in Ukraine, within the context of an ongoing birth cohort study.Methods: The European Collaborative Study (ECS) is an ongoing birth cohort study in which HIV-infected pregnant women identified before or during pregnancy or at delivery were enrolled and their infants prospectively followed. Three centres in Ukraine started enrolling in 2000, with a further three joining in September 2006.Results: Of the 3356 women enrolled, 21% (689) reported current or past injecting drug use (IDU). Most women were diagnosed antenatally and of those, the proportion diagnosed in the first/second trimester increased from 47% in 2000/01 (83/178) to 73% (776/1060) in 2006/07 (p < 0.001); intrapartum diagnosis was associated with IDU (Adjusted odds ratio 4.38; 95% CI 3.19-6.02). The percentage of women not receiving any antiretroviral prophylaxis declined from 18% (36/205) in 2001 to 7% in 2007 (61/843) p < 0.001). Use of sdNVP alone substantially declined after 2003, with a concomitant increase in zidovudine prophylaxis. Median antenatal zidovudine prophylaxis duration increased from 24 to 72 days between 2000 and 2007. Elective caesarean section (CS) rates were relatively stable over time and 34% overall. Mother-to-child transmission (MTCT) rates decreased from 15.2% in 2001 (95% CI 10.2-21.4) to 7.0% in 2006 (95% CI 2.6-14.6). In adjusted analysis, MTCT risk was reduced by 43% with elective CS versus vaginal delivery and by 75% with zidovudine versus no prophylaxis.Conclusion: There have been substantial improvements in use of PMTCT interventions in Ukraine, including earlier diagnosis of HIV-infected pregnant women and increasing coverage with antiretroviral prophylaxis and the initial MTCT rate has more than halved. Future research should focus on hard-to-reach populations such as IDU and on missed opportunities for further reducing the MTCT rate

Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study.

INTRODUCTION: The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures. METHODS: In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged ≥18 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MRI were excluded. Participants also underwent detailed recording of symptoms, and physiological and biochemical tests. The primary outcome was the excess burden of multiorgan abnormalities (two or more organs) relative to controls, with further adjustments for potential confounders. The C-MORE study is ongoing and is registered with ClinicalTrials.gov, NCT04510025. FINDINGS: Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years [SD 12]; 158 [61%] male and 101 [39%] female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years [SD 14]; 30 [58%] male and 22 [42%] female) were included in the analysis. Patients were assessed at a median of 5·0 months (IQR 4·2-6·3) after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MRI were more frequent in patients than in controls (157 [61%] of 259 vs 14 [27%] of 52; p5mg/L, OR 3·55 [1·23-11·88]; padjusted=0·025) than those without multiorgan abnormalities. Presence of lung MRI abnormalities was associated with a two-fold higher risk of chest tightness, and multiorgan MRI abnormalities were associated with severe and very severe persistent physical and mental health impairment (PHOSP-COVID symptom clusters) after hospitalisation. INTERPRETATION: After hospitalisation for COVID-19, people are at risk of multiorgan abnormalities in the medium term. Our findings emphasise the need for proactive multidisciplinary care pathways, with the potential for imaging to guide surveillance frequency and therapeutic stratification. FUNDING: UK Research and Innovation and National Institute for Health Research

A collaborative study to establish the 1st WHO International Standard for human cytomegalovirus for nucleic acid amplification technology.

Variability in the performance of nucleic acid amplification technology (NAT)-based assays presents a significant problem in the diagnosis and management of human cytomegalovirus (HCMV) infections. Here we describe a collaborative study to evaluate the suitability of candidate reference materials to harmonize HCMV viral load measurements in a wide range of NAT assays. Candidate materials comprised lyophilized Merlin virus, liquid Merlin virus, liquid AD169 virus, and purified HCMV Merlin DNA cloned into a bacterial artificial chromosome. Variability in the laboratory mean HCMV concentrations determined for virus samples across the different assays was 2 log10. Variability for the purified DNA sample was higher (>3 log10). The agreement between laboratories was markedly improved when the potencies of the liquid virus samples were expressed relative to the lyophilized virus candidate. In contrast, the agreement between laboratories for the purified DNA sample was not improved. Results indicated the suitability of the lyophilized Merlin virus preparation as the 1st WHO International Standard for HCMV for NAT. It was established in October 2010, with an assigned potency of 5 × 106 International Units (IU) (NIBSC code 09/162). It is intended to be used to calibrate secondary references, used in HCMV NAT assays, in IU

After the fire: Post-pandemic reflections

Over the space of a few months virtually everything we know has been turned on its head. In Wuhan (China) during the closing months of 2019 a spillover event occurred in which the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was transferred from its animal host population into humans 1, 2. Spread mainly by respiratory droplets, the virus has a basic reproduction number (R0) of between 2-6 in an unprotected population making it more contagious than influenza, but considerably less so than measles. As SARS-CoV-2 rapidly spread across the planet, aided by our love of intercontinental travel, the local market outbreak of a mystery respiratory illness became a global pandemic of unimaginable proportions 3. Coronavirus disease 2019 (COVID-19), the illness that occurs in humans as a result of infection with SARS-CoV-2, has dominated the news for most of 2020 to date, and transformed the way in which we live, work, socialise, shop, exercise and communicate. In addition to this, it has placed intensive care medicine at the very centre of healthcare planning in the future, as the pandemic highlighted the weakness in our local, regional and national systems for dealing with crisis of this magnitude. The herculean efforts seen in intensive care units (ICUs) around the world is a testament to the dedication of those in our specialty and those who came to support us in our hour of need. However, for many of us, the situation was (and may still be) overwhelming and unsustainable; none of us would be eager to 2 return to it in a hurry. Once we have all taken a well-earned break, we need to brace ourselves for whatever lies ahead, equipped with the knowledge and experiences gained in during this pandemic

Pregnancy is associated with elevation of liver enzymes in HIV-positive women on antiretroviral therapy.

The objective of this study is to assess whether pregnancy is associated with an increased risk of liver enzyme elevation (LEE) and severe LEE in HIV-positive women on antiretroviral therapy (ART)

The effects of age on associations between markers of HIV progression and markers of metabolic function including albumin, haemoglobin and lipid concentrations.

OBJECTIVES: We investigated whether age modified associations between markers of HIV progression, CD4 T lymphocyte count and HIV RNA viral load (VL), and the following markers of metabolic function: albumin, haemoglobin, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TC). METHODS: A retrospective analysis of data from the United Kingdom Collaborative HIV Cohort was carried out. Analyses were limited to antiretroviral-naïve subjects to focus on the impact of HIV disease itself. A total of 16670 subjects were included in the analysis. Multilevel linear regression models assessed associations between CD4 count/VL and each of the outcomes. Statistical tests for interactions assessed whether associations differed among age groups. RESULTS: After adjustment for gender and ethnicity, there was evidence that lower CD4 count and higher VL were associated with lower TC, LDL-C, haemoglobin and albumin concentrations but higher triglyceride concentrations. Age modified associations between CD4 count and albumin (P 50 years, a 50 cells/μL lower CD4 count correlated with a 2.4 [95% confidence interval (CI) 1.7-3.0], 3.6 (95% CI 3.2-4.0) and 5.1 (95% CI 4.0-6.1) g/L lower haemoglobin concentration and a 0.09 (95% CI 0.07-0.11), 0.12 (95% CI 0.11-0.13) and 0.16 (95% CI 0.13-0.19) g/L lower albumin concentration, respectively. CONCLUSIONS: We present evidence that age modifies associations between CD4 count and plasma albumin and haemoglobin levels. A given reduction in CD4 count was associated with a greater reduction in haemoglobin and albumin concentrations among older people living with HIV. These findings increase our understanding of how the metabolic impact of HIV is influenced by age

The iBRA (implant breast reconstruction evaluation) study: protocol for a prospective multi-centre cohort study to inform the feasibility, design and conduct of a pragmatic randomised clinical trial comparing new techniques of implant-based breast reconstruction.

BACKGROUND: Implant-based breast reconstruction (IBBR) is the most commonly performed reconstructive procedure in the UK. The introduction of techniques to augment the subpectoral pocket has revolutionised the procedure, but there is a lack of high-quality outcome data to describe the safety or effectiveness of these techniques. Randomised controlled trials (RCTs) are the best way of comparing treatments, but surgical RCTs are challenging. The iBRA (implant breast reconstruction evaluation) study aims to determine the feasibility, design and conduct of a pragmatic RCT to examine the effectiveness of approaches to IBBR. METHODS/DESIGN: The iBRA study is a trainee-led research collaborative project with four phases:Phase 1 - a national practice questionnaire (NPQ) to survey current practicePhase 2 - a multi-centre prospective cohort study of patients undergoing IBBR to evaluate the clinical and patient-reported outcomesPhase 3- an IBBR-RCT acceptability survey and qualitative work to explore patients' and surgeons' views of proposed trial designs and candidate outcomes.Phase 4 - phases 1 to 3 will inform the design and conduct of the future RCT All centres offering IBBR will be encouraged to participate by the breast and plastic surgical professional associations (Association of Breast Surgery and British Association of Plastic Reconstructive and Aesthetic Surgeons). Data collected will inform the feasibility of undertaking an RCT by defining current practice and exploring issues surrounding recruitment, selection of comparator arms, choice of primary outcome, sample size, selection criteria, trial conduct, methods of data collection and feasibility of using the trainee collaborative model to recruit patients and collect data. DISCUSSION: The preliminary work undertaken within the iBRA study will determine the feasibility, design and conduct of a definitive RCT in IBBR. It will work with the trainee collaborative to build capacity by creating an infrastructure of research-active breast and plastic surgeons which will facilitate future high-quality research that will ultimately improve outcomes for all women seeking reconstructive surgery. TRIAL REGISTRATION: ISRCTN37664281

Clinical precursors of tics: an EMTICS study

BACKGROUND: Children with Tourette syndrome (TS) often have comorbid disorders, particularly attention-deficit/hyperactivity disorder (ADHD) and obsessive-compulsive disorder (OCD). While subtle premorbid symptoms have been described in various psychiatric disorders, the presence of clinical precursors that may exist before the onset of tics is unknown. This longitudinal study aimed to find clinical precursors of tics by assessing a range of clinical characteristics prior to tic onset in comparison with children without onset of tics. METHODS: A sample of 187 3- to 10-year-old first-degree unaffected relatives of children with TS were followed up to 7 years in the European Multicentre Tics in Children Study (EMTICS). We investigated whether clinical characteristics assessed at baseline predicted tic onset, comparing 126 children without tic onset to 61 children who developed tics. We used the least absolute shrinkage and selection operator (LASSO) method, a penalised logistic regression approach. We also explored sex differences and repeated our analyses in an age- and sex-matched subsample. RESULTS: Children with tic onset were more frequently male (β = -0.36), had higher baseline severity of conduct problems (β = 0.23), autism spectrum disorder symptoms (ASD; β = 0.08), compulsions (β = 0.02) and emotional problems (β = 0.03) compared to children without tic onset. Conduct and ASD problems were male-specific predictors, whereas severity of compulsions and oppositional (β = 0.39) and emotional problems were female-specific predictors. CONCLUSION: This study supports the presence of clinical precursors prior to tic onset and highlights the need of sex-specific monitoring of children at risk of developing tics. This may aid in the earlier detection of tics, particularly in females. We moreover found that tics most often persisted one year after tic onset, in contrast to the common belief that tics are mostly transient

Incomplete reversibility of estimated glomerular filtration rate decline following tenofovir disoproxil fumarate exposure.

BACKGROUND: Tenofovir disoproxil fumarate (TDF) has been linked to renal impairment, but the extent to which this impairment is reversible is unclear. We aimed to investigate the reversibility of renal decline during TDF therapy. METHODS: Cox proportional hazards models assessed factors associated with discontinuing TDF in those with an exposure duration of >6 months. In those who discontinued TDF therapy, linear piecewise regression models estimated glomerular filtration rate (eGFR) slopes before initiation of, during, and after discontinuation of TDF therapy. Factors associated with not achieving eGFR recovery 6 months after discontinuing TDF were assessed using multivariable logistic regression. RESULTS: We observed declines in the eGFR during TDF exposure (mean slopes, -15.7 mL/minute/1.73 m(2)/year [95% confidence interval {CI}, -20.5 to -10.9] during the first 3 months and -3.1 mL/minute/1.73 m(2)/year [95% CI, -4.6 to -1.7] thereafter) and evidence of eGFR increases following discontinuation of TDF therapy (mean slopes, 12.5 mL/minute/1.73 m(2)/year [95% CI, 8.9-16.1] during the first 3 months and 0.8 mL/minute/1.73 m(2)/year [95% CI,.1-1.5] thereafter). Following TDF discontinuation, 38.6% of patients with a decline in the eGFR did not experience recovery. A higher eGFR at baseline, a lower eGFR after discontinuation of TDF therapy, and more-prolonged exposure to TDF were associated with an increased risk of incomplete recovery 6 months after discontinuation of TDF therapy. CONCLUSIONS: This study shows that a decline in the eGFR during TDF therapy was not fully reversible in one third of patients and suggests that prolonged TDF exposure at a low eGFR should be avoided