COVID-19-related mortality and hospital admissions in the VIVALDI study cohort: October 2020 to March 2023.

BACKGROUND: Long-term-care facilities (LTCFs) were heavily affected by COVID-19 early in the pandemic, but the impact of the virus has reduced over time with vaccination campaigns and build-up of immunity from prior infection. OBJECTIVES: To evaluate the mortality and hospital admissions associated with SARS-CoV-2 in LTCFs in England over the course of the VIVALDI study, from October 2020 to March 2023. METHODS: We included residents aged ≥65 years from participating LTCFs who had available follow-up time within the analysis period. We calculated incidence rates (IRs) of COVID-19-linked mortality and hospital admissions per calendar quarter, along with infection fatality ratios (IFRs, within 28 days) and infection hospitalization ratios (IHRs, within 14 days) following positive SARS-CoV-2 test. RESULTS: A total of 26,286 residents were included, with at least one positive test for SARS-CoV-2 in 8513 (32.4%). The IR of COVID-19-related mortality peaked in the first quarter (Q1) of 2021 at 0.47 per 1000 person-days (1 kpd) (around a third of all deaths), in comparison with 0.10 per 1 kpd for Q1 2023 which had a similar IR of SARS-CoV-2 infections. There was a fall in observed IFR for SARS-CoV-2 infections from 24.9% to 6.7% between these periods, with a fall in IHR from 12.1% to 8.8%. The population had high overall IRs for mortality for each quarter evaluated, corresponding to annual mortality probability of 28.8-41.3%. CONCLUSIONS: Standardized real-time monitoring of hospitalization and mortality following infection in LTCFs could inform policy on the need for non-pharmaceutical interventions to prevent transmission.

Characteristics associated with antenatally unidentified small-for-gestational-age fetuses: prospective cohort study nested within DESiGN randomized controlled trial.

OBJECTIVE: To identify the clinical characteristics and patterns of ultrasound use amongst pregnancies with an antenatally unidentified small-for-gestational-age (SGA) fetus, compared with those in which SGA is identified, to understand how to design interventions that improve antenatal SGA identification. METHODS: This was a prospective cohort study of singleton, non-anomalous SGA (birth weight < 10th centile) neonates born after 24 + 0 gestational weeks at 13 UK sites, recruited for the baseline period and control arm of the DESiGN trial. Pregnancy with antenatally unidentified SGA was defined if there was no scan or if the final scan showed estimated fetal weight (EFW) at the 10th centile or above. Identified SGA was defined if EFW was below the 10th centile at the last scan. Maternal and fetal sociodemographic and clinical characteristics were studied for associations with unidentified SGA using unadjusted and adjusted logistic regression models. Ultrasound parameters (gestational age at first growth scan, number and frequency of ultrasound scans) were described, stratified by presence of indication for serial ultrasound. Associations of unidentified SGA with absolute centile and percentage weight difference between the last scan and birth were also studied on unadjusted and adjusted logistic regression, according to time between the last scan and birth. RESULTS: Of the 15 784 SGA babies included, SGA was not identified antenatally in 78.7% of cases. Of pregnancies with unidentified SGA, 47.1% had no recorded growth scan. Amongst 9410 pregnancies with complete data on key maternal comorbidities and antenatal complications, the risk of unidentified SGA was lower for women with any indication for serial scans (adjusted odds ratio (aOR), 0.56 (95% CI, 0.49-0.64)), for Asian compared with white women (aOR, 0.80 (95% CI, 0.69-0.93)) and for those with non-cephalic presentation at birth (aOR, 0.58 (95% CI, 0.46-0.73)). The risk of unidentified SGA was highest among women with a body mass index (BMI) of 25.0-29.9 kg/m2 (aOR, 1.15 (95% CI, 1.01-1.32)) and lowest in those with underweight BMI (aOR, 0.61 (95% CI, 0.48-0.76)) compared to women with BMI of 18.5-24.9 kg/m2 . Compared to women with identified SGA, those with unidentified SGA had fetuses of higher SGA birth-weight centile (adjusted odds for unidentified SGA increased by 1.21 (95% CI, 1.18-1.23) per one-centile increase between the 0th and 10th centiles). Duration between the last scan and birth increased with advancing gestation in pregnancies with unidentified SGA. SGA babies born within a week of the last growth scan had a mean difference between EFW and birth-weight centiles of 19.5 (SD, 13.8) centiles for the unidentified-SGA group and 0.2 (SD, 3.3) centiles for the identified-SGA group (adjusted mean difference between groups, 19.0 (95% CI, 17.8-20.1) centiles). CONCLUSIONS: Unidentified SGA was more common amongst women without an indication for serial ultrasound, and in those with cephalic presentation at birth, BMI of 25.0-29.9 kg/m2 and less severe SGA. Ultrasound EFW was overestimated in women with unidentified SGA. This demonstrates the importance of improving the accuracy of SGA screening strategies in low-risk populations and continuing performance of ultrasound scans for term pregnancies. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Improving antenatal detection of small-for-gestational-age fetus: economic evaluation of Growth Assessment Protocol.

OBJECTIVE: To determine whether the Growth Assessment Protocol (GAP), as implemented in the DESiGN trial, is cost-effective in terms of antenatal detection of small-for-gestational-age (SGA) neonate, when compared with standard care. METHODS: This was an incremental cost-effectiveness analysis undertaken from the perspective of a UK National Health Service hospital provider. Thirteen maternity units from England, UK, were recruited to the DESiGN (DEtection of Small for GestatioNal age fetus) trial, a cluster randomized controlled trial. Singleton, non-anomalous pregnancies which delivered after 24 + 0 gestational weeks between November 2015 and February 2019 were analyzed. Probabilistic decision modeling using clinical trial data was undertaken. The main outcomes of the study were the expected incremental cost, the additional number of SGA neonates identified antenatally and the incremental cost-effectiveness ratio (ICER) (cost per additional SGA neonate identified) of implementing GAP. Secondary analysis focused on the ICER per infant quality-adjusted life year (QALY) gained. RESULTS: The expected incremental cost (including hospital care and implementation costs) of GAP over standard care was £34 559 per 1000 births, with a 68% probability that implementation of GAP would be associated with increased costs to sustain program delivery. GAP identified an additional 1.77 SGA neonates per 1000 births (55% probability of it being more clinically effective). The ICER for GAP was £19 525 per additional SGA neonate identified, with a 44% probability that GAP would both increase cost and identify more SGA neonates compared with standard care. The probability of GAP being the dominant clinical strategy was low (11%). The expected incremental cost per infant QALY gained ranged from £68 242 to £545 940, depending on assumptions regarding the QALY value of detection of SGA. CONCLUSION: The economic case for replacing standard care with GAP is weak based on the analysis reported in our study. However, this conclusion should be viewed taking into account that cost-effectiveness analyses are always limited by the assumptions made. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Salivary Testosterone and Sexual Function and Behavior in Men and Women: Findings from the Third British National Survey of Sexual Attitudes and Lifestyles (Natsal-3).

Using data from the third British National Survey of Sexual Attitudes and Lifestyles (Natsal-3) we examined associations between salivary testosterone (Sal-T) and sexual function and behavior. Single morning saliva samples were self-collected from a subsample of participants aged 18-74 years and analyzed using mass spectrometry. 1,599 men and 2,123 women were included in the analysis (40.6% of those invited to provide a sample). We adjusted for confounders in a stepwise manner: in model 1 we adjusted for age only; model 2 for age, season and relationship status, and model 3 we added BMI and self-reported health. In the fully adjusted models, among men, Sal-T was positively associated with both partnered sex (vaginal sex and concurrent partners) and masturbation. Among women, Sal-T was positively associated with masturbation, the only association with partnered sex was with ever experience of same-sex sex. We found no clear association between Sal-T and sexual function. Our study contributes toward addressing the sparsity of data outside the laboratory on the differences between men and women in the relationship between T and sexual function and behavior. To our knowledge, this is the first population study, among men and women, using a mass spectrometry Sal-T assay to do so.

Trends and predictors of linkage to HIV outpatient care following diagnosis in the era of expanded testing in England, Wales and Northern Ireland: Results of a national cohort study.

OBJECTIVES: We explore trends in linkage to HIV care following diagnosis and investigate the impact of diagnosis setting on linkage in the era of expanded testing. METHODS: All adults (aged ≥ 15 years) diagnosed with HIV between 2005 and 2014 in England, Wales and Northern Ireland (EW&NI) were followed up until the end of 2017. People who died within 1 month of diagnosis were excluded (n = 1009). Trends in linkage to outpatient care (time to first CD4 count) were examined by sub-population and diagnosis setting. Logistic regression identified predictors of delayed linkage of > 1 month, > 3 months and > 1 year post-diagnosis (2012-2014). RESULTS: Overall, 97% (60 250/62 079) of people linked to care; linkage ≤ 1 month was 75% (44 291/59 312), ≤ 3 months was 88% (52 460) and ≤ 1 year was 95% (56 319). Median time to link declined from 15 days [interquartile range (IQR): 4-43] in 2005 to 6 (IQR: 0-20) days in 2014 (similar across sub-populations/diagnosis settings). In multivariable analysis, delayed linkage to care was associated with acquiring HIV through injecting drug use, heterosexual contact or other routes compared with sex between men (> 1 month/3 months/1 year), being diagnosed in earlier years (> 1 month/3 months/1 year) and having a first CD4 ≥ 200 cells/µL (> 3 months/1 year). Diagnosis outside of sexual health clinics, antenatal services and infectious disease units predicted delays of > 1 month. By 3 months, only diagnosis in 'other' settings (prisons, drug services, community and other medical settings) was significant. CONCLUSIONS: Linkage to care following HIV diagnosis is relatively timely in EW&NI. However, non-traditional testing venues should have well-defined referral pathways established to facilitate access to care and treatment.

Protocol for a cluster randomised control trial evaluating the efficacy and safety of treatment for latent tuberculosis infection in recent migrants within primary care: the CATAPuLT trial.

BACKGROUND: The identification and treatment of LTBI is a key component of the WHO's strategy to eliminate TB. Recent migrants from high TB-incidence countries are recognised to be at risk TB reactivation, and many high-income countries have focused on LTBI screening and treatment programmes for this group. However, migrants are the group least likely to complete the LTBI cascade-of-care. This pragmatic cluster-randomised, parallel group, superiority trial investigates whether a model of care based entirely within a community setting (primary care) will improve treatment completion compared with treatment in specialist TB services (secondary care). METHODS: The CATAPuLT trial (Completion and Acceptability of Treatment Across Primary Care and the community for Latent Tuberculosis) randomised 34 general practices in London, England, to evaluate the efficacy and safety of treatment for LBTI in recent migrants within primary care. GP practices were randomised to either provide management for LTBI entirely within primary care (GPs and community pharmacists) or to refer patients to secondary care. The target recruitment number for individuals is 576. The primary outcome is treatment completion (defined as taking at least 90% of antibiotic doses). The secondary outcomes assess adherence, acceptance of treatment, the incidence of adverse effects including drug-induced liver injury, the rates of active TB, patient satisfaction and cost-effectiveness of LTBI treatment. This protocol adheres to the SPIRIT Checklist. DISCUSSION: The CATAPuLT trial seeks to provide implementation research evidence for a patient-centred intervention to improve treatment completion for LTBI amongst recent migrants to the UK. TRIAL REGISTRATION: NCT03069807, March 2017, registered retrospectively.

Where do we diagnose HIV infection? Monitoring new diagnoses made in nontraditional settings in England, Wales and Northern Ireland.

OBJECTIVES: The objectives of the study were to describe 10-year trends in HIV diagnosis setting and to explore predictors of being diagnosed outside a sexual health clinic (SHC). METHODS: Analyses of national HIV surveillance data were restricted to adults (aged ≥ 15 years) diagnosed in 2005-2014 in England, Wales and Northern Ireland. Logistic regression identified factors associated with diagnosis outside an SHC (2011-2014). RESULTS: Between 2005 and 2014, 63 599 adults were newly diagnosed with HIV infection; 83% had a diagnosis setting reported. Most people were diagnosed in SHCs (69%) followed by: medical admissions/accident and emergency (A&E; 8.6%), general practice (6.4%), antenatal services (5.5%), out-patient services (3.6%), infectious disease units (2.7%) and other settings (4.0%). The proportion of people diagnosed outside SHCs increased from 2005 to 2014, overall (from 27% to 32%, respectively) and among men who have sex with men (MSM) (from 14% to 21%) and black African men (from 25% to 37%) and women (from 39% to 52%) (all trend P < 0.001). Median CD4 increased across all settings, but was highest in SHCs (384 cells/µL) and lowest in medical admissions/A&E (94 cells/µL). Predictors of being diagnosed outside SHCs included: acquiring HIV through heterosexual contact [adjusted odds ratio (aOR) 1.99; 95% confidence interval (CI) 1.81-2.18] or injecting drug use (aOR: 3.28; 95% CI: 2.56-4.19; reference: MSM), being diagnosed late (< 350 cells/µL) (aOR: 2.55; 95% CI: 2.36-2.74; reference: diagnosed promptly) and being of older age at diagnosis (35-49 years: aOR: 1.60; 95% CI: 1.39-1.83; ≥ 50 years: aOR: 2.48; 95% CI: 2.13-2.88; reference: 15-24 years). CONCLUSIONS: The proportion of HIV diagnoses made outside SHCs has increased over the past decade in line with evolving HIV testing guidelines. However, the rate of late diagnosis remains high, indicating that further expansion of testing is necessary, as many people may have had missed opportunities for earlier diagnosis.

Factors associated with delayed linkage to care following HIV diagnosis in the WHO European Region.

OBJECTIVES: To describe linkage to HIV care following diagnosis in Europe and to identify factors associated with delayed linkage. METHODS: We analysed data of adults (aged ≥ 15 years) diagnosed with HIV from 2010 to 2014 in 31 European countries. Linkage to care was calculated using the time between HIV diagnosis and first CD4 count. Linkage was considered delayed if the CD4 count was taken more than 3 months after diagnosis. Logistic regression was used to determine factors for delayed linkage. RESULTS: Of the 120 129 adults diagnosed from 2010 to 2014, 4560 were previously diagnosed elsewhere, 808 died within 3 months of diagnosis and 54 731 people were missing CD4 count and/or date information. Among the 60 030 people included, linkage to care within 3 months was 96%. A lower bound (LB) for this was 55%, when those missing CD4 data were assumed not to be linked. Prompt linkage varied significantly by region [Western: 97% (LB: 65%); Central: 90% (LB: 65%); Eastern: 91% (LB: 11%)] and risk group. In multivariable analysis, delayed linkage to care was associated with: acquiring HIV through injecting drug use/heterosexual contact, being diagnosed in Central/Eastern Europe and having a first CD4 count > 200 cells/µL. People of older age at diagnosis and those diagnosed after 2011 were more likely to be linked promptly. Associations differed by region. CONCLUSIONS: Among those with CD4 data available, linkage to care is prompt. However, HIV surveillance must be strengthened and data quality improved, particularly in Eastern Europe. Our findings highlight disparities in care access and significant differences between regions.

Predictors of CD4 cell recovery following initiation of antiretroviral therapy among HIV-1 positive patients with well-estimated dates of seroconversion.

OBJECTIVES: To investigate factors that predict speed of recovery and long-term CD4 cell count in HIV-1 seroconverters initiating combination antiretroviral therapy (cART), and to quantify the influence of very early treatment initiation. We make use of all pre-treatment CD4 counts, because analyses using only a single observation at initiation may be subject to biases. METHODS: We used data from the CASCADE (Concerted Action on SeroConversion to AIDS and Death in Europe) multinational cohort collaboration of HIV-1 seroconverters. We analysed pre- and post-treatment data of patients with seroconversion dates estimated January 2003-March 2014 (n = 7600 for primary analysis) using a statistical model in which the characteristics of recovery in CD4 counts are determined by multiple predictive factors. Secondary analyses were performed incorporating uncertainty in the exact timing of seroconversion to allow more precise estimation of the benefit of very early treatment initiation. RESULTS: 'True' CD4 count at cART initiation was the strongest predictor of CD4 count beyond 3 years on cART. Allowing for lack of complete certainty in the date of seroconversion, CD4 recovery was more rapid for patients in whom treatment was initiated within 4 months. For a given CD4 count, higher viral load (VL) at initiation was strongly associated with higher post-treatment CD4 recovery. For other patient and drug characteristics, associations with recovery were statistically significant but small in magnitude. CONCLUSIONS: CD4 count at cART initiation is the most important factor in predicting post-treatment recovery, but VL provides substantial additional information. If cART is initiated in the first 4 months following seroconversion, recovery of CD4 counts appears to be more rapid.

Salivary Testosterone Levels and Health Status in Men and Women in the British General Population: Findings from the Third National Survey of Sexual Attitudes and Lifestyles (Natsal-3).

CONTEXT: Salivary T (Sal-T) measurement by liquid chromatography-tandem mass spectroscopy resents the opportunity to examine health correlates of Sal-T in a large-scale population survey. OBJECTIVE: This study sought to examine associations between Sal-T and health-related factors in men and women age 18-74 years. DESIGN AND SETTING: Morning saliva samples were obtained from participants in a cross-sectional probability-sample survey of the general British population (Natsal-3). Self-reported health and lifestyle questions were administered as part of a wider sexual health interview. PARTICIPANTS: Study participants included 1599 men and 2123 women. METHODS: Sal-T was measured using liquid chromatography-tandem mass spectroscopy. Linear regression was used to examine associations between health factors and mean Sal-T. RESULTS: In men, mean Sal-T was associated with a range of health factors after age adjustment, and showed a strong independent negative association with body mass index (BMI) in multivariable analysis. Men reporting cardiovascular disease or currently taking medication for depression had lower age-adjusted Sal-T, although there was no association with cardiovascular disease after adjustment for BMI. The decline in Sal-T with increasing age remained after adjustment for health-related factors. In women, Sal-T declined with increasing age; however, there were no age-independent associations with health-related factors or specific heath conditions with the exception of higher Sal-T in smokers. CONCLUSIONS: Sal-T levels were associated, independently of age, with a range of self-reported health markers, particularly BMI, in men but not women. The findings support the view that there is an age-related decline in Sal-T in men and women, which cannot be explained by an increase in ill health. Our results demonstrate the potential of Sal-T as a convenient measure of tissue androgen exposure for population research.

The "3 in 1" Study: Pooling Self-Taken Pharyngeal, Urethral, and Rectal Samples into a Single Sample for Analysis for Detection of Neisseria gonorrhoeae and Chlamydia trachomatis in Men Who Have Sex with Men.

Triple-site testing (using pharyngeal, rectal, and urethral/first-void urine samples) for Neisseria gonorrhoeae and Chlamydia trachomatis using nucleic acid amplification tests detects greater numbers of infections among men who have sex with men (MSM). However, triple-site testing represents a cost pressure for services. MSM over 18 years of age were eligible if they requested testing for sexually transmitted infections (STIs), reported recent sexual contact with either C. trachomatis or N. gonorrhoeae, or had symptoms of an STI. Each patient underwent standard-of-care (SOC) triple-site testing, and swabs were taken to form a pooled sample (PS) (pharyngeal, rectal, and urine specimens). The PS was created using two methods during different periods at one clinic, but we analyzed the data in combination because the sensitivity of the two methods did not differ significantly for C. trachomatis (P = 0.774) or N. gonorrhoeae (P = 0.163). The sensitivity of PS testing (92%) was slightly lower than that of SOC testing (96%) for detecting C. trachomatis (P = 0.167). For N. gonorrhoeae, the sensitivity of PS testing (90%) was significantly lower than that of SOC testing (99%) (P < 0.001). When pharynx-only infections were excluded, the sensitivity of PS testing to detect N. gonorrhoeae infections increased to 94%. Our findings show that pooling of self-taken samples could be an effective and cost-saving method, with high negative predictive values. (Interim results of this study were presented at the BASHH 2013 summer meeting.).

Patterns of sexual mixing with respect to social, health and sexual characteristics among heterosexual couples in England: analyses of probability sample survey data.

Patterns of sexual mixing are major determinants of sexually transmitted infection (STI) transmission, in particular the extent to which high-risk populations mix with low-risk populations. However, patterns of mixing in the general population are poorly understood. We analysed data from a national probability sample survey of households, the Health Survey for England 2010. A total of 943 heterosexual couples living together, where at least one partner was aged between 16-44 years, were included. We used correlation coefficients to measure the strength of similarities between partners with respect to demographic characteristics, general health, health behaviours and sexual history. Males were on average 2 years older than their female partners, although this age difference ranged from a median of 0 years in men aged 16-24 years to a median of 2 years in men aged 35-44 years. A positive correlation between partners was found for all demographic characteristics. With respect to general health and health behaviours, a strongly positive correlation was found between men and women in reporting alcohol consumption at ⩾3 days a week and smoking. Men typically reported greater numbers of sexual partners than their female partner, although men and women with more partners were more likely to mix with each other. We have been able to elucidate the patterns of sexual mixing between men and women living together in England. Mixing based on demographic characteristics was more assortative than sexual characteristics. These data can better inform mathematical models of STI transmission.

Acute kidney injury among HIV-infected patients admitted to the intensive care unit.

We describe the incidence, associations and outcomes of acute kidney injury (AKI) among HIV-infected patients admitted to the intensive care unit (ICU). We retrospectively analysed 223 admissions to an inner-London, University-affiliated ICU between 1999 and 2012, and identified those with AKI and performed multivariate analysis to determine associations with AKI. Of all admissions, 66% were affected by AKI of any severity and 35% developed stage 3 AKI. In multivariate analysis, AKI was associated with chronic kidney disease (odds ratio [OR] = 3.19; p = 0.014), a previous AIDS-defining illness (OR = 1.93; p = 0.039) and the Acute Physiology and Chronic Health Evaluation (APACHE) II score, (OR = 3.49; p = 0.018, if > 30). No associations were demonstrated with use of anti-retroviral medication (including tenofovir), or an individual's HIV viral load or CD4 count. AKI was associated with higher inpatient mortality and longer duration of ICU admission. Among patients with stage 3 AKI, only 41% were alive 90 days after ICU admission. Among survivors, 74% regained good renal function, the remainder were dependent on renal replacement therapy or were left with significant ongoing renal dysfunction. Of note, many patients had baseline serum creatinine concentrations well below published reference ranges. AKI among HIV-infected patients admitted to ICU carries a poor prognosis.

Avascular necrosis in HIV patients: a case-control study.

This study investigates the association of avascular necrosis (AVN) in human immunodeficiency virus (HIV)-positive individuals with possible risk factors, including antiretroviral therapy. Clinic records of all AVN cases diagnosed up to July 2009 in HIV-positive patients attending North Middlesex Hospital, London, UK were retrospectively reviewed. For each case, one control was randomly selected, matched for gender, age, nadir CD4 count and date of HIV diagnosis. Of 15 symptomatic AVN cases identified, eight were in women. Univariate analysis demonstrated significant associations between AVN and a history of systemic steroid use (p = 0.004) and cumulative exposure to protease inhibitor (p = 0.03). Physicians should be aware of the risk of AVN with steroid use, the importance of early diagnosis and avoidance of other risk factors in order to prevent further joint involvement if possible.

Hepatitis C in men who have sex with men in London--a community survey.

OBJECTIVES: For the last 10 years there has been an epidemic of hepatitis C virus (HCV) infection in men who have sex with men (MSM) in Europe, North America and Australia. The majority of those infected are also HIV-positive and it is unclear to what extent HIV-negative MSM are also at increased risk of infection with HCV. This study provides the first examination of the association between HIV and hepatitis C serostatus in a sample of MSM recruited in community settings. METHODS: A total of 1121 participants completed a short questionnaire in 2008/2009 giving demographic and behavioural data, and donated a sample of oral fluid that was subsequently tested for antibodies to selected pathogens (HIV, syphilis and HCV). RESULTS: The seroprevalence of hepatitis C antibody was 2.1% [95% confidence interval (CI) 1.4-3.2%]. It was more common in those with HIV infection [7.7% (95% CI 4.2-12.9%) vs. 1.2% (95% CI 0.6-2.1%) in those without HIV infection; P < 0.001], those with a history of syphilis [12.2% (95% CI 4.6-24.8%) vs. 1.7% (95% CI 1.0-2.6%) in those without such a history; P < 0.001] and those who reported casual unprotected anal intercourse in the previous year [4.1% (95% CI 2.0-7.4%) vs. 1.2% (95% CI 0.5-2.2%) in those who did not report such intercourse; P = 0.01]. There was no relationship between hepatitis C antibody (anti-HCV) status and other demographic variables (age, ethnicity, employment status or education). CONCLUSIONS: The seroprevalence of anti-HCV in HIV-negative MSM (1.2%) was higher, but not significantly higher, than that in the general population (0.67%). The prevalence was significantly higher in those infected with HIV or with previous syphilis infection and in those reporting unprotected anal intercourse. Our findings support current British Association for Sexual Health and HIV guidelines recommending the provision of selective HCV testing in MSM according to individual risk profile.

Trends in attendances to genitourinary medicine services by older women.

We sought to analyse reasons for attendance of older women (defined as aged 46 years and over) to genitourinary (GU) medicine services at two UK clinics. We used KC60 coding data to count new episode attendances by year from 1998 to 2008 and to further dissect reason for attendance in 2827 new episodes during 2003-2008. The total number of new episodes of attendance in older women increased from 167 in 1998 to 701 in 2008. Within this overall increase, there was a stable proportion of acute sexually transmitted infections (STIs) over time, alongside significant increases in the proportion of women requesting STI screening and HIV testing and those attending GU medicine for other reasons, such as dermatological or gynaecological complaints. In our clinic population it was encouraging to see that older women increasingly use GU medicine services for STI screening and HIV testing. Services may need to adapt to older women's specific health-care needs.

A prognostic scoring tool for identification of patients at high and low risk of death from HIV-associated Pneumocystis jirovecii pneumonia.

A prognostic scoring tool (PST) was created to aid prediction of outcome from HIV-associated Pneumocystis jirovecii pneumonia (PCP) using data obtained from 577 episodes of PCP among 540 patients presenting to a specialist HIV treatment centre in London, UK. It used risk factors identifiable at/soon after hospitalization, previously identified as being associated with mortality: repeat episode of PCP, patient's age, haemoglobin (Hb) and oxygen partial pressure (PaO(2)) on admission, presence of medical co-morbidity (Comorb) and of pulmonary Kaposi sarcoma (PKS). The derived PST was 25.5+(age in years/10) + 2 (if a repeat episode of PCP) + 3 (if Comorb present) + 4 (if PKS detected) - PaO(2) (kPa) - Hb (g/dL), and produced scores that ranged between 0 and 19. Patients were divided into five groups according to their prognostic score: 0-3.9 = group 1 (0% mortality), 4-7.9 = group 2 (3% mortality), 8-10.9 = group 3 (9% mortality), 11-14.9 = group 4 (29% mortality) and ≥ 15 = group 5 (52% mortality). This PST facilitates rapid identification of patients early in their hospitalization who have mild or severe HIV-associated PCP and who are at high and low risk of in-hospital death from PCP. The PST may aid assessment of severity of illness and in directing treatment strategies, but requires validation in patient cohorts from other health-care institutions.

Survival of HIV-infected patients admitted to the intensive care unit in the era of highly active antiretroviral therapy.

We retrospectively studied outcomes for HIV-infected patients admitted to the intensive care unit (ICU) between January 1999 and June 2009. Patient demographics, receipt of highly active antiretroviral therapy (HAART), reason for ICU admission and survival to ICU and hospital discharge were recorded. Comparison was made against outcomes for general medical patients contemporaneously admitted to the same ICU. One hundred and ninety-two HIV-infected patients had 222 ICU admissions; 116 patients required mechanical ventilation (MV) and 43 required renal replacement therapy. ICU admission was due to an HIV-associated diagnosis in 113 patients; 37 had Pneumocystis pneumonia. Survival to ICU discharge and hospital discharge for HIV-infected patients was 78% and 70%, respectively, and was 75% and 68% among 2065 general medical patients with 2274 ICU admissions; P = 0.452 and P = 0.458, respectively. HIV infection was newly diagnosed in 42 patients; their ICU and hospital survival was 69% and 57%, respectively. From multivariable analysis, factors associated with ICU survival were patient's age (odds ratio [OR] = 0.74 [95% confidence interval (CI) = 0.53-1.02] per 10-year increase), albumin (OR = 1.05 [1.00-1.09] per 1 g/dL increase), Acute Physiology and Chronic Health Evaluation (APACHE) II score (OR = 0.55 [0.35-0.87] per 10 unit increase), receipt of HAART (OR = 2.44 [1.01-4.94]) and need for MV (OR = 0.14 [0.06-0.36]). In the era of HAART, HIV-infected patients should be offered ICU admission if it is likely to be of benefit.

A critical review of methods for the assessment of patient-level interactions in individual participant data meta-analysis of randomized trials, and guidance for practitioners.

OBJECTIVE: Treatments may be more effective in some patients than others, and individual participant data (IPD) meta-analysis of randomized trials provides perhaps the best method of investigating treatment-covariate interactions. Various methods are used; we provide a comprehensive critique and develop guidance on method selection. STUDY DESIGN AND SETTING: We searched MEDLINE to identify all frequentist methods and appraised them for simplicity, risk of bias, and power. IPD data sets were reanalyzed. RESULTS: Four methodological categories were identified: PWT: pooling of within-trial covariate interactions; OSM: "one-stage" model with a treatment-covariate interaction term; TDCS: testing for difference between covariate subgroups in their pooled treatment effects; and CWA: combining PWT with meta-regression. Distinguishing across- and within-trial information is important, as the former may be subject to ecological bias. A strategy is proposed for method selection in different circumstances; PWT or CWA are natural first steps. The OSM method allows for more complex analyses; TDCS should be avoided. Our reanalysis shows that different methods can lead to substantively different findings. CONCLUSION: The choice of method for investigating interactions in IPD meta-analysis is driven mainly by whether across-trial information is considered for inclusion, a decision, which depends on balancing possible improvement in power with an increased risk of bias.

Seasonal variation in mortality of Pneumocystis jirovecii pneumonia in HIV-infected patients.

A seasonal variation in the presentation of Pneumocystis jirovecii pneumonia (PCP) has been reported and a previous study from this centre noted a seasonal variation in mortality rates. This study examined seasonal influences (including climatic factors) within-host factors (clinical and laboratory-derived variables), the infectious burden of P. jirovecii in bronchoalveolar lavage (BAL) fluid, the presence of dihydropteroate synthase (DHPS) mutations in P. jirovecii, variations in knowledge and skills of junior medical staff, and mortality in 547 episodes of PCP occurring in 494 HIV-infected patients. The overall mortality rate was 13.5%. There was a seasonal variation in mortality: highest in autumn (21.2%) and lowest in spring (9.7%), P = 0.047. After adjustment was made for prognostic factors previously identified as being associated with mortality (increasing patient age, second/third episode of PCP, low haemoglobin, low PaO(2), presence of medical co-morbidity and pulmonary Kaposi sarcoma), there was no seasonal association with mortality, P = 0.249. The quantity of P. jirovecii DNA in BAL fluid showed no evidence of seasonal variation, P = 0.67; DHPS mutations were identified with equal frequency in each season and the mortality rate for February and August (when junior medical staff arrive in new posts) was 16.7%, only slightly greater than for other months (13.0%).