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Summary: Background: Long COVID is the patient-coined term for the persistent symptoms of COVID-19 illness for weeks, months or years following the acute infection. There is a large burden of long COVID globally from self-reported data, but the epidemiology, causes and treatments remain poorly understood. Primary care is used to help identify and treat patients with long COVID and therefore Electronic Health Records (EHRs) of past COVID-19 patients could be used to help fill these knowledge gaps. We aimed to describe the incidence and differences in demographic and clinical characteristics in recorded long COVID in primary care records in England. Methods: With the approval of NHS England we used routine clinical data from over 19 million adults in England linked to SARS-COV-2 test result, hospitalisation and vaccination data to describe trends in the recording of 16 clinical codes related to long COVID between November 2020 and January 2023. Using OpenSAFELY, we calculated rates per 100,000 person-years and plotted how these changed over time. We compared crude and adjusted (for age, sex, 9 NHS regions of England, and the dominant variant circulating) rates of recorded long COVID in patient records between different key demographic and vaccination characteristics using negative binomial models. Findings: We identified a total of 55,465 people recorded to have long COVID over the study period, which included 20,025 diagnoses codes and 35,440 codes for further assessment. The incidence of new long COVID records increased steadily over 2021, and declined over 2022. The overall rate per 100,000 person-years was 177.5 cases in women (95% CI: 175.5–179) and 100.5 in men (99.5–102). The majority of those with a long COVID record did not have a recorded positive SARS-COV-2 test 12 or more weeks before the long COVID record. Interpretation: In this descriptive study, EHR recorded long COVID was very low between 2020 and 2023, and incident records of long COVID declined over 2022. Using EHR diagnostic or referral codes unfortunately has major limitations in identifying and ascertaining true cases and timing of long COVID. Funding: This research was supported by the National Institute for Health and Care Research (NIHR) (OpenPROMPT: COV-LT2-0073).

Summary: Background: Long COVID is a major problem affecting patient health, the health service, and the workforce. To optimise the design of future interventions against COVID-19, and to better plan and allocate health resources, it is critical to quantify the health and economic burden of this novel condition. We aimed to evaluate and estimate the differences in health impacts of long COVID across sociodemographic categories and quantify this in Quality-Adjusted Life-Years (QALYs), widely used measures across health systems. Methods: With the approval of NHS England, we utilised OpenPROMPT, a UK cohort study measuring the impact of long COVID on health-related quality-of-life (HRQoL). OpenPROMPT invited responses to Patient Reported Outcome Measures (PROMs) using a smartphone application and recruited between November 2022 and October 2023. We used the validated EuroQol EQ-5D questionnaire with the UK Value Set to develop disutility scores (1-utility) for respondents with and without Long COVID using linear mixed models, and we calculated subsequent Quality-Adjusted Life-Months (QALMs) for long COVID. Findings: The total OpenPROMPT cohort consisted of 7575 individuals who consented to data collection, with which we used data from 6070 participants who completed a baseline research questionnaire where 24.6% self-reported long COVID. In multivariable regressions, long COVID had a consistent impact on HRQoL, showing a higher likelihood or odds of reporting loss in quality-of-life (Odds Ratio (OR): 4.7, 95% CI: 3.72–5.93) compared with people who did not report long COVID. Reporting a disability was the largest predictor of losses of HRQoL (OR: 17.7, 95% CI: 10.37–30.33) across survey responses. Self-reported long COVID was associated with an 0.37 QALM loss. Interpretation: We found substantial impacts on quality-of-life due to long COVID, representing a major burden on patients and the health service. We highlight the need for continued support and research for long COVID, as HRQoL scores compared unfavourably to patients with conditions such as multiple sclerosis, heart failure, and renal disease. Funding: This research was supported by the National Institute for Health and Care Research (NIHR) (OpenPROMPT: COV-LT2-0073).

Natural killer cells play important roles in the immune response to human cytomegalovirus infection. Here the authors implicate donor-derived liver resident natural killer cells in the control of human cytomegalovirus infection by analysis of perfusates derived from human transplant livers.

The modelling of BVOC chemistry strongly affects how doubling of BVOC emissions affects climate. Lower oxidant depletion with state-of-science chemistry leads to 43% smaller positive forcing from smaller methane increases and cloud albedo decreases.

Objective To implement complex, PINCER (pharmacist led information technology intervention) prescribing indicators, on a national scale with general practice data to describe the impact of the covid-19 pandemic on safe prescribing.Design Population based, retrospective cohort study using federated analytics.Setting Electronic general practice health record data from 56.8 million NHS patients by use of the OpenSAFELY platform, with the approval of the National Health Service (NHS) England.Participants NHS patients (aged 18-120 years) who were alive and registered at a general practice that used TPP or EMIS computer systems and were recorded as at risk of at least one potentially hazardous PINCER indicator.Main outcome measure Between 1 September 2019 and 1 September 2021, monthly trends and between practice variation for compliance with 13 PINCER indicators, as calculated on the first of every month, were reported. Prescriptions that do not adhere to these indicators are potentially hazardous and can cause gastrointestinal bleeds; are cautioned against in specific conditions (specifically heart failure, asthma, and chronic renal failure); or require blood test monitoring. The percentage for each indicator is formed of a numerator of patients deemed to be at risk of a potentially hazardous prescribing event and the denominator is of patients for which assessment of the indicator is clinically meaningful. Higher indicator percentages represent potentially poorer performance on medication safety.Results The PINCER indicators were successfully implemented across general practice data for 56.8 million patient records from 6367 practices in OpenSAFELY. Hazardous prescribing remained largely unchanged during the covid-19 pandemic, with no evidence of increases in indicators of harm as captured by the PINCER indicators. The percentage of patients at risk of potentially hazardous prescribing, as defined by each PINCER indicator, at mean quarter 1 (Q1) 2020 (representing before the pandemic) ranged from 1.11% (age ≥65 years and non-steroidal anti-inflammatory drugs) to 36.20% (amiodarone and no thyroid function test), while Q1 2021 (representing after the pandemic) percentages ranged from 0.75% (age ≥65 years and non-steroidal anti-inflammatory drugs) to 39.23% (amiodarone and no thyroid function test). Transient delays occurred in blood test monitoring for some medications, particularly angiotensin-converting enzyme inhibitors (where blood monitoring worsened from a mean of 5.16% in Q1 2020 to 12.14% in Q1 2021, and began to recover in June 2021). All indicators substantially recovered by September 2021. We identified 1 813 058 patients (3.1%) at risk of at least one potentially hazardous prescribing event.Conclusion NHS data from general practices can be analysed at national scale to generate insights into service delivery. Potentially hazardous prescribing was largely unaffected by the covid-19 pandemic in primary care health records in England.

Background: The COVID-19 pandemic has had a significant impact on delivery of NHS care. We have developed the OpenSAFELY Service Restoration Observatory (SRO) to develop key measures of primary care activity and describe the trends in these measures throughout the COVID-19 pandemic. Methods: With the approval of NHS England, we developed an open source software framework for data management and analysis to describe trends and variation in clinical activity across primary care electronic health record (EHR) data on 48 million adults. Results: We produced 11 measures reflective of clinical activity in general practice. A substantial drop in activity was observed in all measures at the outset of the COVID-19 pandemic. By April 2021, the median rate had recovered to within 15% of the median rate in April 2019 in six measures. The remaining measures showed a sustained drop, ranging from a 18.5% reduction in medication reviews to a 42.0% reduction in blood pressure monitoring. Three measures continued to show a sustained drop by December 2021. Conclusions: The COVID-19 pandemic was associated with a substantial change in primary care activity across the measures we developed, with recovery in most measures. We delivered an open source software framework to describe trends and variation in clinical activity across an unprecedented scale of primary care data. We will continue to expand the set of key measures to be routinely monitored using our publicly available NHS OpenSAFELY SRO dashboards with near real-time data. Funding: This research used data assets made available as part of the Data and Connectivity National Core Study, led by Health Data Research UK in partnership with the Office for National Statistics and funded by UK Research and Innovation (grant ref MC_PC_20058).The OpenSAFELY Platform is supported by grants from the Wellcome Trust (222097/Z/20/Z); MRC (MR/V015757/1, MC_PC-20059, MR/W016729/1); NIHR (NIHR135559, COV-LT2-0073), and Health Data Research UK (HDRUK2021.000, 2021.0157).

Summary: Background: The COVID-19 pandemic disrupted healthcare and may have impacted ethnic inequalities in healthcare. We aimed to describe the impact of pandemic-related disruption on ethnic differences in clinical monitoring and hospital admissions for non-COVID conditions in England. Methods: In this population-based, observational cohort study we used primary care electronic health record data with linkage to hospital episode statistics data and mortality data within OpenSAFELY, a data analytics platform created, with approval of NHS England, to address urgent COVID-19 research questions. We included adults aged 18 years and over registered with a TPP practice between March 1, 2018, and April 30, 2022. We excluded those with missing age, sex, geographic region, or Index of Multiple Deprivation. We grouped ethnicity (exposure), into five categories: White, Asian, Black, Other, and Mixed. We used interrupted time-series regression to estimate ethnic differences in clinical monitoring frequency (blood pressure and Hba1c measurements, chronic obstructive pulmonary disease and asthma annual reviews) before and after March 23, 2020. We used multivariable Cox regression to quantify ethnic differences in hospitalisations related to diabetes, cardiovascular disease, respiratory disease, and mental health before and after March 23, 2020. Findings: Of 33,510,937 registered with a GP as of 1st January 2020, 19,064,019 were adults, alive and registered for at least 3 months, 3,010,751 met the exclusion criteria and 1,122,912 were missing ethnicity. This resulted in 14,930,356 adults with known ethnicity (92% of sample): 86.6% were White, 7.3% Asian, 2.6% Black, 1.4% Mixed ethnicity, and 2.2% Other ethnicities. Clinical monitoring did not return to pre-pandemic levels for any ethnic group. Ethnic differences were apparent pre-pandemic, except for diabetes monitoring, and remained unchanged, except for blood pressure monitoring in those with mental health conditions where differences narrowed during the pandemic. For those of Black ethnicity, there were seven additional admissions for diabetic ketoacidosis per month during the pandemic, and relative ethnic differences narrowed during the pandemic compared to the White ethnic group (Pre-pandemic hazard ratio (HR): 0.50, 95% confidence interval (CI) 0.41, 0.60, Pandemic HR: 0.75, 95% CI: 0.65, 0.87). There was increased admissions for heart failure during the pandemic for all ethnic groups, though highest in those of White ethnicity (heart failure risk difference: 5.4). Relatively, ethnic differences narrowed for heart failure admission in those of Asian (Pre-pandemic HR 1.56, 95% CI 1.49, 1.64, Pandemic HR 1.24, 95% CI 1.19, 1.29) and Black ethnicity (Pre-pandemic HR 1.41, 95% CI: 1.30, 1.53, Pandemic HR: 1.16, 95% CI 1.09, 1.25) compared with White ethnicity. For other outcomes the pandemic had minimal impact on ethnic differences. Interpretation: Our study suggests that ethnic differences in clinical monitoring and hospitalisations remained largely unchanged during the pandemic for most conditions. Key exceptions were hospitalisations for diabetic ketoacidosis and heart failure, which warrant further investigation to understand the causes. Funding: LSHTM COVID-19 Response Grant (DONAT15912).

Since early 2020, the COVID-19 pandemic has had a dramatic impact on the way we live, with European countries having to introduce unprecedented measures to protect public health. As with all areas of life, drug consumption, related harms and drug markets have been impacted, as have the drug services established to respond to drug-related problems. Since the start of the pandemic in March 2020, the European Monitoring Centre for Drugs and Drug Addiction instigated three rapid assessment studies to identify the initial impact and implications of COVID-19 on drug markets, use, harms and drug services in the community and in prisons. Findings from these studies revealed that the pandemic and associated health prevention measures implemented by the countries impacted drug markets and use differently depending on the different periods and events throughout the pandemic, but also according to particular drugs or user characteristics. Most drug services remained operational throughout the pandemic in order to assure continuity of care. This was achieved by innovation and adaptation of their services, especially during the different lockdown periods. Thus, the results from these rapid assessments provide a glimpse into new developments in the drugs field across European countries emerging both during and in response to the pandemic, and which could have important implications for the future.

IntroductionIn this study, we used proton Magnetic Resonance Spectroscopy (1H-MRS) to determine the neuronal function in the thalamus and primary somatosensory (S1) cortex in different subgroups of DPN, including subclinical- and painful-DPN.MethodOne-hundred and ten people with type 1 diabetes [20 without DPN (no-DPN); 30 with subclinical-DPN; 30 with painful-DPN; and 30 with painless-DPN] and 20 healthy volunteers, all of whom were right-handed men, were recruited and underwent detailed clinical and neurophysiological assessments. Participants underwent Magnetic Resonance Imaging at 1.5 Tesla with two 1H-MRS spectra obtained from 8 ml cubic volume voxels: one placed within left thalamus to encompass the ventro-posterior lateral sub-nucleus and another within the S1 cortex.ResultsIn the thalamus, participants with painless-DPN had a significantly lower NAA:Cr ratio [1.55 + 0.22 (mean ± SD)] compared to all other groups [HV (1.80 ± 0.23), no-DPN (1.85 ± 0.20), sub-clinical DPN (1.79 ± 0.23), painful-DPN (1.75 ± 0.19), ANOVA p

Abstract Background Congenital cytomegalovirus (CMV) is the most common congenital infection globally, however information about CMV is not routinely included in antenatal education in the United Kingdom. This feasibility study aimed to gather the essential data needed to design and power a large randomised controlled trial (RCT) to investigate the efficacy of a digital intervention in reducing the risk of CMV acquisition in pregnancy. In order to do this, we carried out a single-centre RCT, which explored the knowledge, attitudes and risk reduction behaviours in women in the intervention and treatment as usual groups, pre- and post-intervention. Methods CMV seronegative women living with a child less than four years old, receiving antenatal care at a single UK tertiary centre, were randomised to the digital intervention or ‘treatment as usual’ groups. Participants completed questionnaires before the digital intervention and after and at 34 gestational weeks, and responses within groups and between groups were compared using tailored randomisation tests. CMV serology was tested in the first trimester and at the end of pregnancy. Results Of the 878 women screened, 865 samples were analysed with 43% (n = 372) being CMV seronegative and therefore eligible to take part in the RCT; of these, 103 (27.7%) women were enrolled and 87 (84%) of these completed the study. Most participants (n = 66; 64%) were unfamiliar with CMV at enrolment, however at 34 gestational weeks, women in the intervention group (n = 51) were more knowledgeable about CMV compared to the treatment as usual group (n = 52) and reported engaging in activities that may increase the risk of CMV transmission less frequently. The digital intervention was highly acceptable to pregnant women. Overall, four participants seroconverted over the course of the study: two from each study group. Conclusions A large multi-centre RCT investigating the efficacy of a CMV digital intervention is feasible in the United Kingdom; this study has generated essential data upon which to power such a study. This single-centre feasibility RCT demonstrates that a digital educational intervention is associated with increase in knowledge about CMV and can result in behaviour change which may reduce the risk of CMV acquisition in pregnancy. Trial registration Clinicaltrials.gov, NCT03511274 , Registered 27.04.18, http://www.Clinicaltrials.gov

Abstract Pulmonary mucormycosis (PM) is a rare but rapidly progressive fungal infection associated with high mortality. A review of the literature suggests that pleural effusions and pneumothoraces are uncommon manifestations associated with distant dissemination. Combined surgical interventions and prolonged antifungal therapy constitute the standard first‐line management, with significantly poorer outcomes seen in patients managed with medical therapy alone. Here, we report an unusual case of PM complicated by hydropneumothorax in an immunocompromised patient, in whom comorbidities and disease burden precluded surgical debridement. His disease was ultimately treated with intravenous amphotericin B and maintenance posaconazole after adjunctive drainage. This clinical experience highlights the efficacy of antifungal therapy alone in the treatment of potentially fatal cases of PM unsuitable for surgery.

Cytomegalovirus (CMV) is one of opportunistic infections post solid organ transplant and remains a cause of morbidity and mortality. Mammalian target of rapamycin inhibitors has a theoretical antiviral advantage compared to conventional immunosuppression. The primary outcome was to assess the viremic response and kidney function in a cohort of kidney transplant recipients (KTRs) with difficult to manage CMV infection when converted to sirolimus. We retrospectively analyzed the outcome of substituting sirolimus for mycophenolate mofetil (MMF) or tacrolimus in 18 KTR with difficult to manage, resistant/recurrent CMV viremia unresponsive or intolerant of standard anti-CMV treatment, or immunosuppression reduction. Safety and feasibility of sirolimus conversion were assessed through studying CMV viral loads, creatinine levels, immunosuppression, antiviral therapy, kidney function, and acute rejection episodes before and after starting sirolimus as well as the sirolimus side effects. Data were collected from the hospital filing system. The Wilcoxon matched-pairs signed-rank test and Friedman test were used for statistical analysis. The area under the curve for Log10 CMV viral load (log10 copies/ml) was significantly higher before than after the sirolimus switch (P = 0.0156). The median number of days on antiviral treatment was reduced after conversion to sirolimus [48 days (0–95); vs. 68 days (21–146)]. Acute rejection occurred more commonly before than after starting sirolimus [n =5 (27.7%) vs. n = 2 (11.1%)]. Median serum creatinine before conversion to sirolimus was 175.5 μmol/L (79–243), and showed no deterioration three months and one year after conversion [148 (69–271) and 162.5 (69–287) μmol/L, respectively, P = 0.002]. The use of sirolimus, often alongside tacrolimus and after discontinuation of MMF, is a useful strategy in treating recurrent CMV viremia without provoking rejection.

Cytomegalovirus (CMV) is the commonest cause of congenital infection and particularly so among infants born to HIV-infected women. Studies of congenital CMV infection (cCMVi) pathogenesis are complicated by the presence of multiple infecting maternal CMV strains, especially in HIV-positive women, and the large, recombinant CMV genome. Using newly developed tools to reconstruct CMV haplotypes, we demonstrate anatomic CMV compartmentalization in five HIV-infected mothers and identify the possibility of congenitally transmitted genotypes in three of their infants. A single CMV strain was transmitted in each congenitally infected case, and all were closely related to those that predominate in the cognate maternal cervix. Compared to non-transmitted strains, these congenitally transmitted CMV strains showed statistically significant similarities in 19 genes associated with tissue tropism and immunomodulation. In all infants, incident superinfections with distinct strains from breast milk were captured during follow-up. The results represent potentially important new insights into the virologic determinants of early CMV infection.

Background: Smoking rather than injecting heroin has become more common over the last 20 years. Although there is an increasing body of evidence describing high levels of chronic obstructive pulmonary disease (COPD) in people who smoke heroin, there is limited evidence documenting the impact of the long-term condition on this population group. Aim: This study aimed to describe the experiences of people who smoke heroin with COPD in Liverpool, UK. Design & setting: Participants were purposefully sampled for this qualitative study. They included adults enrolled in an opioid replacement clinic run by Addaction in Liverpool, who had already engaged with spirometry testing for COPD as part of a previous study. Method: Semi-structured interviews were performed with participants with spirometrically confirmed COPD in opioid replacement clinics. Data were analysed using a framework analysis approach. Results: Sixteen potential participants were invited to take part in the study, of which 10 agreed and were interviewed. Three themes common to all interviews were identified: functional measures of lung health that impacted on their activities of daily living; inhaler and medication perceptions with erratic use that was not concordant with their prescription; and the impact of difficulties accessing care. Conclusion: These findings, along with previous studies highlighting the prevalence of COPD in this population, warrant efforts to integrate community COPD and opioid replacement services to improve outcomes for this vulnerable population.

Background Congenital cytomegalovirus (CMV) is the most common infectious cause of congenital disability, which can cause lifelong impairments including sensorineural hearing loss and developmental delay. This study aimed to explore the experiences of parenting a child with congenital CMV and the impact this has on families.Methods Ten parents living with a child with congenital CMV in the UK participated in semistructured interviews and data were analysed using thematic analysis.Results The findings illustrate that delays in making the diagnosis of congenital CMV are associated with parental distress and lack of knowledge about CMV among medical professionals can exacerbate this distress. Parents expressed frustration about not knowing about CMV infection during their pregnancies and therefore not having the opportunity to take measures to reduce their risk of acquiring CMV while pregnant. The uncertainty about the long-term outcomes of children with congenital CMV adds additional emotional burden for parents. Family and wider societal networks have the potential to facilitate coping and alleviate stress, but the lack of awareness of CMV acts as a barrier to receiving support from family and friends.Conclusions There is a need to increase awareness of CMV among medical professionals, pregnant women and wider society to improve the diagnostic process and to provide better support for families caring for children with congenital CMV infection.

Summary: Background: Globally, an estimated 15·6 million people inject drugs. We aimed to investigate global variation in the age profile of people who inject drugs (PWID), identify country-level factors associated with age of PWID, and assess the association between injecting drug use (IDU) in young people and rates of injecting and sexual risk behaviours at the country level. Methods: We derived data from a previously published global systematic review done in April, 2016 (and updated in June, 2017) on the percentage of young PWID, duration of IDU, average age of PWID, average age at IDU initiation, and the percentage of PWID reporting sexual and injecting risk behaviours. We also derived national development indicators from World Bank data. We estimated the percentage of young PWID for each country, using a random-effects meta-analysis (DerSimonian-Laird methodology) and generated pooled regional and global estimates for all indicators of IDU in young people. We used univariable and multivariable generalised linear models to test for associations between the age indicators and country urban population growth, youth unemployment percentage, the percentage of PWID who are female, the percentage of the general population aged 15–24 years, Gini coefficient, opioid substitution therapy coverage (per PWID per year), gross domestic product (GDP) per capita (US$1000), and sexual and injecting risk behaviours. Findings: In the original systematic review, data on age of PWID was reported in 741 studies across 93 countries. Globally, 25·3% (95% uncertainty interval [UI] 19·6–31·8) of PWID were aged 25 years or younger. The highest percentage of young PWID resided in eastern Europe (43·4%, 95% UI 39·4–47·4), and the lowest percentage resided in the Middle East and north Africa (6·9%, 5·1–8·8). At the country level, in multivariable analysis higher GDP was associated with longer median injecting duration (0·11 years per $1000 GDP increase, 95% CI 0·04–0·18; p=0·002), and older median age of PWID (0·13 years per $1000 increase, 0·06–0·20; p

Abstract Background and aims Despite advances in our knowledge of effective services for people who use drugs over the last decades globally, coverage remains poor in most countries, while quality is often unknown. This paper aims to discuss the historical development of successful epidemiological indicators and to present a framework for extending them with additional indicators of coverage and quality of harm reduction services, for monitoring and evaluation at international, national or subnational levels. The ultimate aim is to improve these services in order to reduce health and social problems among people who use drugs, such as human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infection, crime and legal problems, overdose (death) and other morbidity and mortality. Methods and results The framework was developed collaboratively using consensus methods involving nominal group meetings, review of existing quality standards, repeated email commenting rounds and qualitative analysis of opinions/experiences from a broad range of professionals/experts, including members of civil society and organisations representing people who use drugs. Twelve priority candidate indicators are proposed for opioid agonist therapy (OAT), needle and syringe programmes (NSP) and generic cross-cutting aspects of harm reduction (and potentially other drug) services. Under the specific OAT indicators, priority indicators included ‘coverage’, ‘waiting list time’, ‘dosage’ and ‘availability in prisons’. For the specific NSP indicators, the priority indicators included ‘coverage’, ‘number of needles/syringes distributed/collected’, ‘provision of other drug use paraphernalia’ and ‘availability in prisons’. Among the generic or cross-cutting indicators the priority indicators were ‘infectious diseases counselling and care’, ‘take away naloxone’, ‘information on safe use/sex’ and ‘condoms’. We discuss conditions for the successful development of the suggested indicators and constraints (e.g. funding, ideology). We propose conducting a pilot study to test the feasibility and applicability of the proposed indicators before their scaling up and routine implementation, to evaluate their effectiveness in comparing service coverage and quality across countries. Conclusions The establishment of an improved set of validated and internationally agreed upon best practice indicators for monitoring harm reduction service will provide a structural basis for public health and epidemiological studies and support evidence and human rights-based health policies, services and interventions.

BACKGROUND:Human cytomegalovirus (HCMV) can be managed by monitoring HCMV DNA in the blood and giving valganciclovir when viral load exceeds a defined value. We hypothesised that such pre-emptive therapy should occur earlier than the standard 3000 genomes/ml (2520 IU/ml) when a seropositive donor transmitted virus to a seronegative recipient (D+R-) following solid organ transplantation (SOT). METHODS:Our local protocol was changed so that D+R- SOT patients commenced valganciclovir once the viral load exceeded 200 genomes/ml; 168 IU/ml (new protocol). The decision point remained at 3000 genomes/ml (old protocol) for the other two patient subgroups (D+R+, D-R+). Virological outcomes were assessed three years later, when 74 D+R- patients treated under the old protocol could be compared with 67 treated afterwards. The primary outcomes were changes in peak viral load, duration of viraemia and duration of treatment in the D+R- group. The secondary outcome was the proportion of D+R- patients who developed subsequent viraemia episodes. FINDINGS:In the D+R- patients, the median values of peak viral load (30,774 to 11,135 genomes/ml, p

As one of the main drivers for climate change, it is important to understand changes in anthropogenic aerosol emissions and evaluate the climate impact. Anthropogenic aerosols have affected global climate while exerting a much larger influence on regional climate by their short lifetime and heterogeneous spatial distribution. In this study, the effective radiative forcing (ERF), which has been accepted as a useful index for quantifying the effect of climate forcing, was evaluated to understand the effects of aerosol on regional climate over a historical period (1850–2014). Eastern United States (EUS), Western European Union (WEU), and Eastern Central China (ECC), are regions that predominantly emit anthropogenic aerosols and were analyzed using Coupled Model Intercomparison Project 6 (CMIP6) simulations implemented within the framework of the Aerosol Chemistry Model Intercomparison Project (AerChemMIP) in the UK’s Earth System Model (UKESM1). In EUS and WEU, where industrialization occurred relatively earlier, the negative ERF seems to have been recovering in recent decades based on the decreasing trend of aerosol emissions. Conversely, the radiative cooling in ECC seems to be strengthened as aerosol emission continuously increases. These aerosol ERFs have been largely attributed to atmospheric rapid adjustments, driven mainly by aerosol-cloud interactions rather than direct effects of aerosol such as scattering and absorption.

Summary: Background: Sharing of equipment used for injecting drug use (IDU) is a substantial cause of disease burden and a contributor to blood-borne virus transmission. We did a global multistage systematic review to identify the prevalence of IDU among people aged 15–64 years; sociodemographic characteristics of and risk factors for people who inject drugs (PWID); and the prevalence of HIV, hepatitis C virus (HCV), and hepatitis B virus (HBV) among PWID. Methods: Consistent with the GATHER and PRISMA guidelines and without language restrictions, we systematically searched peer-reviewed databases (MEDLINE, Embase, and PsycINFO; articles published since 2008, latest searches in June, 2017), searched the grey literature (websites and databases, searches between April and August, 2016), and disseminated data requests to international experts and agencies (requests sent in October, 2016). We searched for data on IDU prevalence, characteristics of PWID, including gender, age, and sociodemographic and risk characteristics, and the prevalence of HIV, HCV, and HBV among PWID. Eligible data on prevalence of IDU, HIV antibody, HBsAg, and HCV antibody among PWID were selected and, where multiple estimates were available, pooled for each country via random effects meta-analysis. So too were eligible data on percentage of PWID who were female; younger than 25 years; recently homeless; ever arrested; ever incarcerated; who had recently engaged in sex work, sexual risk, or injecting risk; and whose main drugs injected were opioids or stimulants. We generated regional and global estimates in line with previous global reviews. Findings: We reviewed 55 671 papers and reports, and extracted data from 1147 eligible records. Evidence of IDU was recorded in 179 of 206 countries or territories, which cover 99% of the population aged 15–64 years, an increase of 31 countries (mostly in sub-Saharan Africa and the Pacific Islands) since a review in 2008. IDU prevalence estimates were identified in 83 countries. We estimate that there are 15·6 million (95% uncertainty interval [UI] 10·2–23·7 million) PWID aged 15–64 years globally, with 3·2 million (1·6–5·1 million) women and 12·5 million (7·5–18·4 million) men. Gender composition varied by location: women were estimated to comprise 30·0% (95% UI 28·5–31·5) of PWID in North America and 33·4% (31·0–35·6) in Australasia, compared with 3·1% (2·1–4·1) in south Asia. Globally, we estimate that 17·8% (10·8–24·8) of PWID are living with HIV, 52·3% (42·4–62·1) are HCV-antibody positive, and 9·1% (5·1–13·2) are HBV surface antigen positive; there is substantial geographic variation in these levels. Globally, we estimate 82·9% (76·6–88·9) of PWID mainly inject opioids and 33·0% (24·3–42·0) mainly inject stimulants. We estimate that 27·9% (20·9–36·8) of PWID globally are younger than 25 years, 21·7% (15·8–27·9) had recently (within the past year) experienced homelessness or unstable housing, and 57·9% (50·5–65·2) had a history of incarceration. Interpretation: We identified evidence of IDU in more countries than in 2008, with the new countries largely consisting of low-income and middle-income countries in Africa. Across all countries, a substantial number of PWID are living with HIV and HCV and are exposed to multiple adverse risk environments that increase health harms. Funding: Australian National Drug and Alcohol Research Centre, Australian National Health and Medical Research Council, Open Society Foundation, World Health Organization, the Global Fund, and UNAIDS.

Summary: Background: People who inject drugs (PWID) are a key population affected by the global HIV and hepatitis C virus (HCV) epidemics. HIV and HCV prevention interventions for PWID include needle and syringe programmes (NSP), opioid substitution therapy (OST), HIV counselling and testing, HIV antiretroviral therapy (ART), and condom distribution programmes. We aimed to produce country-level, regional, and global estimates of coverage of NSP, OST, HIV testing, ART, and condom programmes for PWID. Methods: We completed searches of peer-reviewed (MEDLINE, Embase, and PsycINFO), internet, and grey literature databases, and disseminated data requests via social media and targeted emails to international experts. Programme and survey data on each of the named interventions were collected. Programme data were used to derive country-level estimates of the coverage of interventions in accordance with indicators defined by WHO, UNAIDS, and the UN Office on Drugs and Crime. Regional and global estimates of NSP, OST, and HIV testing coverage were also calculated. The protocol was registered on PROSPERO, number CRD42017056558. Findings: In 2017, of 179 countries with evidence of injecting drug use, some level of NSP services were available in 93 countries, and there were 86 countries with evidence of OST implementation. Data to estimate NSP coverage were available for 57 countries, and for 60 countries to estimate OST coverage. Coverage varied widely between countries, but was most often low according to WHO indicators (200 needle-syringes distributed per PWID and >40 OST recipients per 100 PWID). Interpretation: Coverage of HIV and HCV prevention interventions for PWID remains poor and is likely to be insufficient to effectively prevent HIV and HCV transmission. Scaling up of interventions for PWID remains a crucial priority for halting the HIV and HCV epidemics. Funding: Open Society Foundations, The Global Fund, WHO, UNAIDS, United Nations Office on Drugs and Crime, Australian National Drug and Alcohol Research Centre, University of New South Wales Sydney.

A wireless accelerometer has been used in conjunction with a dedicated 3T neonatal MRI system installed on a Neonatal Intensive Care Unit to measure in-plane rotation which is a common problem with neonatal MRI. Rotational data has been acquired in real-time from phantoms simultaneously with MR images which shows that the wireless accelerometer can be used in close proximity to the MR system. No artifacts were observed on the MR images from the accelerometer or from the MR system on the accelerometer output. Initial attempts to correct the raw data using the measured rotational angles have been performed, but further work will be required to make a robust correction algorithm.

To estimate the seroprevalence of cytomegalovirus (CMV), Epstein Barr virus (EBV) and varicella zoster virus (VZV) among pregnant women in Bradford by ethnic group and country of birth.A stratified random sample of 949 pregnant women enrolled in the Born in Bradford birth cohort was selected to ensure sufficient numbers of White UK born women, Asian UK born women and Asian women born in Asia. Serum samples taken at 24-28 weeks' gestation were tested for CMV IgG, EBV IgG and VZV IgG. Each woman completed a questionnaire which included socio-demographic information.CMV seroprevalence was 49% among the White British women, 89% among South Asian UK born women and 98% among South Asian women born in South Asia. These differences remained after adjusting for socio-demographic factors. In contrast, VZV seroprevalence was 95% among women born in the UK but significantly lower at 90% among South Asian women born in Asia. EBV seroprevalence was 94% overall and did not vary by ethnic group/country of birth.Although about half of White British women are at risk of primary CMV infection in pregnancy and the associated increased risk of congenital infection, most congenital CMV infections are likely to be in children born to South Asian women with non-primary infection during pregnancy. South Asian women born in South Asia are at risk of VZV infection during pregnancy which could produce congenital varicella syndrome or perinatal chickenpox. Differences in CMV and VZV seroprevalence by ethnic group and country of birth must be taken into account when universal immunisation against these viruses is contemplated.

Progress in the fight against the HIV/AIDS epidemic is hindered by our failure to elucidate the precise reasons for the onset of immunodeficiency in HIV-1 infection. Increasing evidence suggests that elevated immune activation is associated with poor outcome in HIV-1 pathogenesis. However, the basis of this association remains unclear. Through ex vivo analysis of virus-specific CD8(+) T-cells and the use of an in vitro model of naïve CD8(+) T-cell priming, we show that the activation level and the differentiation state of T-cells are closely related. Acute HIV-1 infection induces massive activation of CD8(+) T-cells, affecting many cell populations, not only those specific for HIV-1, which results in further differentiation of these cells. HIV disease progression correlates with increased proportions of highly differentiated CD8(+) T-cells, which exhibit characteristics of replicative senescence and probably indicate a decline in T-cell competence of the infected person. The differentiation of CD8(+) and CD4(+) T-cells towards a state of replicative senescence is a natural process. It can be driven by excessive levels of immune stimulation. This may be part of the mechanism through which HIV-1-mediated immune activation exhausts the capacity of the immune system.