Behaviour changes following HIV diagnosis among men who have sex with men in the era of treatment as prevention: data from a prospective study.

We described the longitudinal changes in sexual behaviour and associated factors among newly diagnosed with HIV men who have sex with men participating in a prospective observational study from a London HIV clinic (2015-2018). Participants self-completed questionnaires at baseline, months 3 and 12. Information collected included socio-demographic, sexual behaviour, health, lifestyle and social support. Trends in sexual behaviours over one year following diagnosis and associated factors were assessed using generalized estimating equations with logit link. Condomless sex (CLS) dropped from 62.2% at baseline to 47.6% at month-three but increased again to 61.8% at month-12 (p-trend = 0.790). Serodiscordant-CLS increased between month-three and month-12 (from 13.1% to 35.6%, p-trend < 0.001). The prevalence of serodiscordant-CLS with high risk of transmitting to their partners at month-three was 10.7%. CLS was higher among men who reported recreational drug use (adjusted Odds Ratio (aOR) 3.03, 95%CI 1.47-6.24, p = 0.003), those with undetectable viral load (aOR 2.17, 95%CI 1.22-3.84, p = 0.008) and those who agreed with a statement "condoms are not necessary when HIV viral load is undetectable" (aOR 3.41, 95%CI 1.58-7.38, p = 0.002). MSM continued to engage in CLS after HIV diagnosis, which coincided with U = U publications and increased throughout the study.

Reflections on a specialist HIV menopause service: Experiences of managing menopause in women living with HIV: Experiences of managing menopause in women living with HIV.

OBJECTIVES: We describe here characteristics and clinical outcomes of women living with HIV attending an HIV menopause service. METHODS: This was a retrospective case note review of women attending the monthly HIV menopause clinic from January 2015 to July 2018. RESULTS: In all, 55 women attended the service. The overall mean age was 49 years; 50% were black and 20% had a previous AIDS-defining condition. All were on antiretroviral therapy (ART); the median CD4 count was 678 cells/µL; 93% had a viral load < 50 copies/mL; 7% had previous hepatitis C infection; 27% had a history of smoking; 45% had risk factors or existing cardiovascular disease; 24% had a mental health condition. The median duration of symptoms before clinic attendance was 18 months. Vasomotor symptoms (84%), menstrual cycle changes (62%), psychological (56%) and urogenital symptoms (29%) were reported. Twenty-two per cent had early menopause or premature ovarian insufficiency. The mean age at attendance of women diagnosed with menopause (n = 24) was 52 years. However, their average duration of symptoms prior to review was 28 months. A total of 61% had osteopenia/osteoporosis, 73% received menopausal hormone therapy (MHT), and 73% had symptomatic improvement, although 58% of these required higher doses of MHT. Median time on MHT was 10 months. Five patients had their ART modified. No serious MHT adverse effects were observed. CONCLUSIONS: Menopausal hormone therapy uptake was high, with most women observing an improvement in symptoms. Comorbidities were common, highlighting the need for integrated care based on a woman's needs. The long delay from initial symptoms to treatment demonstrates the need for better access to specialist advice for women experiencing menopause.

FRAX assessment in people ageing with HIV.

OBJECTIVES: Current British HIV Association (BHIVA) guidelines recommend the use of FRAX for the routine assessment of bone fracture risk in people living with HIV over 50 years of age every 3 years. Bone mineral density measurement with dual-energy X-ray absorptiometry (DXA) scan is recommended for those with increased fracture risk (FRAX major > 10%). Our objectives were to estimate the prevalence of and risk factors for osteoporosis in a population of PLWH aged > 50 years and assess the utility of FRAX in predicting the presence of DXA-proven osteoporosis in this cohort. METHODS: This was a cross-sectional study of a cohort of PLWH aged > 50 years attending the Chelsea and Westminster Hospital and who had a DXA scan between January 2009 and December 2018. FRAX scores were calculated using the Sheffield algorithm. Multiple regression models and Cohen's kappa values were used to assess risk factors for osteoporosis and agreement between FRAX and DXA scan results, respectively. RESULTS: In all, 744 patients were included (92.9% male, mean age 56 ± 5 years). The prevalence rates of osteoporosis (at DXA scans) and osteopenia were 12.2% and 63.7%, respectively. FRAX major was > 10% in only two patients, while 90/91 (98.9%) patients with osteoporosis had a normal FRAX score. The presence of osteoporosis was significantly associated with low body mass index and estimated glomerular filtration rate (p < 0.05). CONCLUSION: Our results indicate that FRAX scores did not predict the presence of osteoporosis in our population of PLWH over 50 years of age and therefore FRAX scores may not be the appropriate tool to define eligibility to perform DXA scans in PLWH.

Demographics and incidence of anal squamous cell carcinoma in people living in high HIV prevalence geographical areas.

OBJECTIVES: Anal squamous cell carcinoma (ASCC) is an uncommon cancer that is rapidly increasing in incidence. HIV is a risk factor in the development of ASCC, and it is thought that the rapidly increasing incidence in men is related to increasing numbers of people living with HIV (PLWH). We undertook a population-based study comparing the demographics and incidence of ASCC in patients residing high HIV prevalence areas in England to patients living in average HIV prevalence areas in England. METHODS: This is a cross-sectional study following the 'Strengthening the Reporting of Observational Studies in Epidemiology' statement. Demographic data and incidence rates of ASCC within Clinical Commissioning Groups (CCGs) between 2013 and 2018 were extracted from the Cancer Outcomes and Services Dataset. CCGs were then stratified by HIV prevalence from data given by Public Health England, and high HIV prevalence geographical areas were compared with average HIV geographical areas. RESULTS: Patients in high HIV areas were more likely to be young and male with higher levels of social deprivation. Incidence rates in men between 2013 and 2017 were higher in high HIV areas than average HIV areas with a rapidly increasing incidence rates in early-stage disease and a 79.1% reduction in incidence of metastatic stage 4 disease.Whereas women in high HIV areas had lower ASCC incidence than the national average and a low incidence of early-stage disease; however, metastatic disease in women had quintupled in incidence in high HIV areas since 2013. CONCLUSIONS: Patients presenting with ASCC in high HIV geographical areas have different demographics to patients presenting in average HIV geographical areas. This may be related to screening programmes for PLWH in high HIV areas.

Fetal fractional limb volumes in pregnancies following bariatric surgery.

INTRODUCTION: Obesity rates have reached an epidemic level and bariatric surgery is the most effective method of sustainable weight loss. Pregnancy following bariatric surgery is associated with an increased prevalence of small babies. The objective of the study is to compare the fetal fat distribution, as assessed by fractional arm and thigh volume using three-dimensional ultrasonography, in pregnancies following maternal bariatric surgery with those without such history. MATERIAL AND METHODS: This is a prospective, longitudinal, observational study conducted in a Maternity Unit in the UK. The study included 189 pregnant women; 63 with previous bariatric surgery [27 restrictive (13 with gastric band, 14 with sleeve gastrectomy) and 36 malabsorptive procedures] and 126 with no previous surgery but similar maternal booking body mass index. Fetal arm and thigh volume were obtained at 30-33 and 35-37 weeks' gestation and fractional limb volumes were calculated using a commercially available software. Women underwent a 75 g, 2 h oral glucose tolerance test at 28-31 weeks of gestation. RESULTS: Overall, adjusted fetal arm and thigh volume were smaller in the post-bariatric, compared to the no surgery, group and this was more marked in women who had undergone a previous sleeve gastrectomy (P < .001 and P = .002, respectively) or a malabsorptive procedure (P < .001 for both). There was a strong positive correlation between maternal fasting/post-prandial (2 h) glucose levels, at the time of the oral glucose tolerance test, and arm and thigh volume at both 30-33 and 35-37 weeks (P < .01 for all). CONCLUSIONS: The study has demonstrated that in the third trimester of pregnancy, fetuses of women with previous bariatric surgery have smaller fractional limb volumes, therefore less soft tissue, compared to fetuses of women without such surgery and this may be related to the lower maternal glucose levels seen in the former pregnancies.

The cost of care for people living with stable HIV in Croatia and the efficiency of EmERGE.

AIM: To estimate the cost-effectiveness of the EmERGE Pathway of Care for medically stable people living with HIV (PLHIV) at the University Hospital for Infectious Diseases (UHID), Zagreb. The Pathway includes a mobile application enabling individuals to communicate with their caregivers. METHODS: This study involving 293 participants collected data on the use of HIV outpatient services one year before and after EmERGE implementation. In departments supporting HIV outpatients, a micro-costing exercise was performed to calculate unit costs. These were combined with mean use of HIV services per patient year (MPPY) to estimate average annual costs. Primary outcomes were CD4 count, viral load, and secondary outcomes were patient activation, PAM13; and quality of life, PROQOL-HIV. Information on out-of-pocket expenditures was also collected. RESULTS: Outpatient visits decreased by 17%, from 4.0 (95% CI 3.8-4.3) to 3.3 MPPY (95% CI 3.1-3.5). Tests, including CD4 count, decreased, all contributing to a 33% reduction of annual costs: 7139 HRK (95% CI 6766-7528) to 4781 HRK (95% CI 4504-5072). Annual costs including anti-retroviral drugs (ARVs) decreased by 5%: 43101 HRK (95% CI 42728-43,490) to 40 743 HRK (95% CI 40466-41,034). ARVs remain the main cost driver in stable PLHIV. Primary and secondary outcomes did not change substantially between periods. CONCLUSION: EmERGE Pathway was a cost-saving intervention associated with changes in management, and a reduction in outpatient visits, tests, and costs. ARV costs dominated costs. Future efficiencies are possible if EmERGE is introduced to other PLHIV across the UHID and if ARV prices are reduced.

An evaluation study of the Becton-Dickinson ProbeTec Qx (BDQx) Trichomonas vaginalis trichomoniasis molecular diagnostic test in two large, urban STD services.

OBJECTIVES: The BASHH guidelines recommend molecular tests to aid diagnosis of Trichomonas vaginalis (TV) infection; however many clinics continue to use relatively insensitive techniques (pH, wet-prep microscopy (WPM) and culture). Our objectives were to establish a laboratory pathway for TV testing with the Becton-Dickinson Qx (BDQx) molecular assay, to determine TV prevalence and to identify variables associated with TV detection. METHODS: A prospective study of 901 women attending two urban sexual health services for STI testing was conducted. Women were offered TV BDQx testing in addition to standard of care. Data collected were demographics, symptoms, results of near-patient tests and BDQx results for TV, Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (GC). Women with any positive TV result were treated and followed up for test of cure (TOC). RESULTS: 901 women had a TV BDQx test. 472 (53%) were white, 143 (16%) black and 499 (55%) were symptomatic. Infections detected by BDQx were: 11 TV (1.2%), three GC (0.3%) and 44 CT (4.9%). Of the 11 BDQx-detected TV infections, 8 (73%) were in patients of black ethnicity. Of these, four of seven cases (57%) were WPM-positive. All patients received treatment and nine of nine (100%) were BDQx-negative at TOC. In univariate analysis, only black ethnicity was associated with likelihood of a positive TV BDQx result (relative risk (RR) 10.2 (95% CI 2.15 to 48.4)). CONCLUSIONS: The use of the BDQ enhanced detection of TV in asymptomatic and symptomatic populations. Cost-effective implementation of the test will rely on further work to reliably detect demographic and clinical variables that predict positivity.

Antenatal atazanavir: a retrospective analysis of pregnancies exposed to atazanavir.

INTRODUCTION: There are few data regarding the tolerability, safety, or efficacy of antenatal atazanavir. We report our clinical experience of atazanavir use in pregnancy. METHODS: A retrospective medical records review of atazanavir-exposed pregnancies in 12 London centres between 2004 and 2010. RESULTS: There were 145 pregnancies in 135 women: 89 conceived whilst taking atazanavir-based combination antiretroviral therapy (cART), "preconception" atazanavir exposure; 27 started atazanavir-based cART as "first-line" during the pregnancy; and 29 "switched" to an atazanavir-based regimen from another cART regimen during pregnancy. Gastrointestinal intolerance requiring atazanavir cessation occurred in five pregnancies. Self-limiting, new-onset transaminitis was most common in first-line use, occurring in 11.0%. Atazanavir was commenced in five switch pregnancies in the presence of transaminitis, two of which discontinued atazanavir with persistent transaminitis. HIV-VL < 50 copies/mL was achieved in 89.3% preconception, 56.5% first-line, and 72.0% switch exposures. Singleton preterm delivery (<37 weeks) occurred in 11.7% preconception, 9.1% first-line, and 7.7% switch exposures. Four infants required phototherapy. There was one mother-to-child transmission in a poorly adherent woman. CONCLUSIONS: These data suggest that atazanavir is well tolerated and can be safely prescribed as a component of combination antiretroviral therapy in pregnancy.

CCR5 antagonism impacts vaccination response and immune profile in HIV-1 infection.

Maraviroc (MVC) is the first licensed antiretroviral therapeutic agent to target a host cell surface molecule, and successful HIV-1 entry blockade by this C-C chemokine receptor type 5 (CCR5)-antagonist potentiates immunomodulation. We hypothesized that MVC intensification impacts immunization responses, T-cell phenotype, function and delayed type hypersensitivity (DTH) in HIV-1(+) subjects. A 24-wk, double-blinded, placebo-controlled study of the addition of MVC to suppressive antiretroviral therapy in HIV-1(+) persons was performed. Subjects received DTH tests, intramuscular tetanus, meningococcal and oral cholera immunizations. Antibody titers, T-cell function and phenotype were assessed. Of 157 patients referred, 47 were randomized 1:1; MVC:placebo. MVC enhanced meningococcal neo-immunization, blunted cholera response and expedited lymphoproliferation to tetanus boost, without affecting recall humoral response. Anti-HIV-1 group-specific antigen (Gag) and tetanus toxoid (TTox) function improved significantly, HIV-1-associated CD8 T-cell skewing normalized, and the percentage of late-stage and major histocompatibility complex (MHC) class II expressing CD4 T-cells increased. Activated CD4(+) CD38(+) human leukocyte antigen (HLA)-DR(+) T-cells declined, and costimulation shifted to coinhibition. DTH was unchanged. Maraviroc intensification, through antagonism of the cell surface molecule CCR5, favorably influences immune profiles of HIV-1(+) patients, supporting its immunomodulatory use in HIV-1 infection and potentially in other immunologically relevant settings.

Short Communication: Predictive Value of HIV-Related Versus Traditional Risk Factors for Coronary Atherosclerosis in People Aging with HIV.

Cardiovascular disease (CVD) is an important cause of morbidity in people living with HIV (PLWH). We compared the predictive value of HIV-related and traditional CVD risk factors to assess which factors best predict the presence of subclinical coronary atherosclerosis in PLWH. This is a cross-sectional study in PLWH over 50 years of age who performed computed tomography coronary artery calcium (CAC) scoring between 2009 and 2019 at Chelsea and Westminster Hospital. The following outcomes were analyzed: CAC = 0 (no calcification), CAC >0 (any calcification), CAC >100 (moderate calcification), and CAC >400 (severe calcification). Univariate and multivariate logistic regression analyses were performed to assess predictors of coronary calcification. A total of 744 patients were included (mean age 56 ± 5.7 years, 94.8% male, 84% white). A CAC >0 was found in 392 (52.7%), CAC >100 in 90 (12.1%), and CAC >400 in 42 (5.6%) subjects. CAC >100 was strongly associated with hypertension [odds ratio, OR: 2.91, (95% confidence interval: 1.93-4.36), p < .001], dyslipidemia [2.71 (1.81-4.06), p < .001], and diabetes [2.53 (1.29-4.96), p = .01]. Regarding HIV-specific factors, a significant association was found with exposure (>6 years) to protease inhibitors [1.67 (1.06-2.61), p = .05], whereas exposure to tenofovir (>8 years) was negatively associated with CAC >100 [0.54 (0.30-0.98), p = .05]. Despite the high prevalence of hypertension (45.4%) only 21.5% were on antihypertensives, whereas only 29.2% of eligible candidates were receiving lipid-lowering drugs for primary prevention of CVD. Traditional cardiometabolic risk factors remain the strongest predictors of coronary atherosclerosis in PLWH as in the general population. These results underscore the importance of optimizing treatment of hypertension and promoting primary prevention strategies that may be underused in PLWH.

Impact of inhalation injury on outcomes in critically ill burns patients: 12-year experience at a regional burns centre.

INTRODUCTION: Burns inhalation injury increases the attributable mortality of burns related trauma. However, diagnostic uncertainties around bronchoscopically graded severity, and its effect on outcomes, remain. This study evaluated the impact of different bronchoscopic burns inhalation injury grades on outcomes. METHODS: A single-centre cohort study of all patients admitted to the London Burns centre intensive care unit (BICU) over 12 years. Demographic data, burn and burns inhalation injury characteristics, and ICU-related parameters were collected retrospectively. The primary outcome was mortality. Secondary outcomes were hospital and ICU lengths of stay. The impact of pneumonia was determined. Univariate and multivariable Cox's proportional hazards regression analyses informed factors predicting mortality. RESULTS: Burns inhalation injury was diagnosed in 84 of 231 (36%) critically ill burns patients; 20 mild (grade 1), 41 severe (grades 2/3) and 23 unclassified bronchoscopically. Median (IQR) total body surface area burned (TBSA) was 20% (10-40). Mortality was significantly higher in patients with burns inhalation injury vs those without burns inhalation injury (38/84 [45%] vs 35/147 [24%], p < 0.001). Patients with pneumonia had a higher mortality than those without (34/125 [27%] vs 8/71 [11%], p = 0.009). In multivariable analysis, severe burns inhalation injury significantly increased mortality (adjusted HR=2.14, 95%CI: 1.12-4.09, p = 0.022), compared with mild injury (adjusted HR=0.58, 95% CI: 0.18-1.86, p = 0.363). Facial burns (adjusted HR=3.13, 95%CI: 1.69-5.79, p < 0.001), higher TBSA (adjusted HR=1.05, 95%CI: 1.04-1.06, p < 0.001) and older age (adjusted HR=1.04, 95%CI: 1.02-1.07, p < 0.001) also independently predicted mortality, though pneumonia did not. CONCLUSIONS: Severe burns inhalation injury is a significant risk factor for mortality in critically ill burns patients. However, pneumonia did not increase mortality from burns inhalation injury. This work confirms prior implications of bronchoscopically graded burns inhalation injury. Further study is suggested, through registries, into the diagnostic accuracy and reliability of bronchoscopy in burns related lung injury.

Evaluating the long-term impact of an antimicrobial stewardship programme in a Central London mixed medical and surgical intensive care unit.

Background: Antimicrobial overuse causes increased antimicrobial resistance in ICUs; antimicrobial stewardship programmes (ASPs) aim to optimize usage. Following an MDR Acinetobacter baumannii (MRAb) outbreak in 2008, an ASP was implemented at a London ICU, and then continued as a long-term programme. This study aimed to determine long-term changes in antimicrobial prescribing 9 years on. Methods: Data were collected from ICU patients in 2008 immediately before ASP implementation, and thereafter for 6 month cohort periods in 2010-2011, 2012 and 2017. Antimicrobial usage in DDD per 1000 occupied bed days (OBD) were compared. Multivariate linear regression models for antimicrobial days were fitted, adjusting for APACHE II score and patient days. Antimicrobial resistance in Pseudomonas aeruginosa (as an indicator organism) was compared across cohort periods. Findings: Across 400 patients over 9 years, antimicrobial use changed significantly (P < 0.011) and remained lower in all post-ASP cohorts compared with pre-ASP [(2008; 1827 DDD/1000 OBD), (2010; 1264 DDD/1000 OBD), (2012; 1270 DDD/1000 OBD) and (2017; 1566 DDD/1000 OBD)]. There was reduction in usage of all antimicrobial classes except ß-lactams (where there was no significant increase nor decrease, P = 0.178) and aminoglycosides (where there was a significant increase in usage, P < 0.0001). The latter was temporally associated with restrictions on specific carbapenems. There was an increase in carbapenem-resistant P. aeruginosa in 2012 only (P = 0.028) but not subsequently. Conclusions: Following ASP implementation after an outbreak of MRAb, reduced antimicrobial prescribing was maintained 9 years on. We identify several factors influencing successful long-term maintenance of ASPs in ICUs.

The efficiency of the EmERGE platform for medically stable people living with HIV in Portugal.

Background: The aim of this study was to calculate the cost-effectiveness of the EmERGE Pathway of Care for medically stable people living with HIV in the Hospital Capuchos, Centro Hospitalar Universitário de Lisboa Central (HC-CHLC). The app enables individuals to receive HIV treatment information and communicate with caregivers. Methods: This before-and-after study collected the use of services data 1 year before implementation and after implementation of EmERGE from November 1, 2016, to October 30, 2019. Departmental unit costs were calculated and linked to mean use of outpatient services per patient-year (MPPY). Annual costs per patient-year were combined with primary (CD4 count; viral load) and secondary outcomes (PAM-13; PROQOL-HIV). Results: Five hundred eighty-six EmERGE participants used HIV outpatient services. Annual outpatient visits decreased by 35% from 3.1 MPPY (95% confidence interval [CI]: 3.0-3.3) to 2.0 (95% CI: 1.9-2.1) as did annual costs per patient-year from €301 (95% CI: €288-€316) to €193 (95% CI: €182-€204). Laboratory tests and costs increased by 2%, and radiology investigations decreased by 40% as did costs. Overall annual cost for HIV outpatient services decreased by 5% from €2093 (95% CI: €2071-€2112) to €1984 (95% CI: €1968-€2001); annual outpatient costs decreased from €12,069 (95% CI: €12,047-€12,088) to €11,960 (95% CI: €11,944-€11,977), with 83% of annual cost because of antiretroviral therapy (ART). Primary and secondary outcome measures did not differ substantially between periods. Conclusions: The EmERGE Pathway produced cost savings after implementation-extended to all people living with HIV additional savings are likely to be produced, which can be used to address other needs. Antiretroviral drugs (ARVs) were the main cost drivers and more expensive in Portugal compared with ARV costs in the other EmERGE sites.

Efficiency of the EmERGE Pathway of Care in Five European HIV Centres.

OBJECTIVE: We aimed to calculate the efficiency of the EmERGE Pathway of Care in five European HIV clinics, developed and implemented for medically stable people living with HIV. METHODS: Participants were followed up for 1 year before and after implementation of EmERGE, between April 2016 and October 2019. Micro-costing studies were performed in the outpatient services of the clinics. Unit costs for outpatient services were calculated in national currencies and converted to US$ 2018 OECD purchasing parity prices to enable between clinic comparisons in terms of outcomes and costs. Unit costs were linked to the mean use of services for medically stable people living with HIV,  before and after implementation of EmERGE. Primary outcome measures were CD4 count and viral load; secondary outcomes were patient activation (PAM13) and quality of life (PROQOL-HIV). Out-of-pocket expenditure data were collected. RESULTS: There were 2251 participants: 87-93% were male, mean age at entry was 41-47 years. Medically stable people living with HIV had outpatient visits in four sites which decreased by 9-31% and costs by 5-33%; visits and costs increased by 8% in one site, which had to revert back to face-to-face visits. Antiretroviral drugs comprised 83-91% of annual costs: the Portuguese site had the highest antiretroviral drug costs in US$ purchasing parity prices. Primary and secondary outcome measures of participants did not change during the study. CONCLUSIONS: EmERGE is acceptable and provided cost savings in different socio-economic settings. Antiretroviral drug costs remain the main cost drivers in medically stable people living with HIV. While antiretroviral drug prices in local currencies did not differ that much between countries, conversion to US$ purchasing parity prices revealed antiretroviral drugs were more expensive in the least wealthy countries. This needs to be taken into consideration when countries negotiate drug prices with pharmaceutical vendors. Greater efficiencies can be anticipated by extending the use of the EmERGE Pathway to people with complex HIV infection or other chronic diseases. Extending such use should be systematically monitored, implementation should be evaluated and funding should be provided to monitor and evaluate future changes in service provision.

The Role of Demographics, Social Deprivation and Ethnicity on Anal Squamous Cell Carcinoma Incidence in England.

Anal Squamous Cell Carcinoma (ASCC) is an HPV-related malignancy with increasing incidence in high-income economies. Although ethnicity and social deprivation are known to be risk factors in other malignancies, little is known about socioeconomic status and risk of ASCC. This is a cross-sectional study following the STROBE Statement. Demographic data from the English Clinical Outcomes and Services Dataset (COSD) were extracted for all patients diagnosed with ASCC in England between 2013 and 2018. Outcomes included ethnicity, social deprivation, staging and treatment. This study included 5457 patients. Incidence increased by 23.4% in 5 years, with female incidence increasing more rapidly than male incidence (28.6% vs. 13.5%). Men were more likely to present with early staging (p < 0.001) and have surgery as their only treatment (p < 0.001). The rate of incidence of Stage 1 tumours in men was 106.9%; however, women had the greatest increase in metastatic tumours (76.1%). Black Caribbean and Black African patients were more likely to present at an earlier age with later staging (p < 0.001) and social deprivation was associated with younger age (p < 0.001). ASCC incidence is rapidly increasing in patterns consistent with two separate populations: one male with early staging, the other female and related to social deprivation and ethnicity factors.

Lactate dehydrogenase activity staining demonstrates time-dependent immune cell infiltration in human ex-vivo burn-injured skin.

Burn injuries constitute one of the most serious accidental injuries. Increased metabolic rate is a hallmark feature of burn injury. Visualising lactate dehydrogenase (LDH) activity has been previously used to identify metabolic activity differences, hence cell viability and burn depth in burn skin. LDH activity was visualised in injured and uninjured skin from 38 sub-acute burn patients. LDH activity aided the identification of spatially correlating immunocompetent cells in a sub-group of six patients. Desorption Electrospray Ionisation Mass Spectrometry Imaging (DESI MSI) was used to describe relative lactate and pyruvate abundance in burned and uninjured tissue. LDH activity was significantly increased in the middle and deep regions of burnt skin compared with superficial areas in burnt skin and uninjured tissue and positively correlated with post-burn time. Regions of increased LDH activity showed high pyruvate and low lactate abundance when examined with DESI-MSI. Areas of increased LDH activity exhibited cellular infiltration, including CD3 + and CD4 + T-lymphocytes and CD68 + macrophages. Our data demonstrate a steady increase in functional LDH activity in sub-acute burn wounds linked to cellular infiltration. The cell types associated are related to tissue restructuring and inflammation. This region in burn wounds is likely the focus of dysregulated inflammation and hypermetabolism.

The International Index of Erectile Function: development of an adapted tool for use in HIV-positive men who have sex with men.

INTRODUCTION: Erectile dysfunction is common in HIV-positive men who have sex with men (MSM). A standardized scale is needed to assess erectile function in clinical practice and research studies. AIM: The International Index of Erectile Function (IIEF) is a widely accepted tool for assessing erectile function designed for heterosexual men. We modified the tool for MSM. We present an analysis of internal consistency of the questionnaire in an HIV-positive cohort. METHODS: The adapted questionnaire included modified questions within each of the five domains of the IIEF: (i) erectile function, (ii) intercourse satisfaction, (iii) orgasmic function, (iv) sexual desire, and (v) overall satisfaction with sex. MSM at seven European HIV treatment centers completed the questionnaire. MAIN OUTCOME MEASURES: Responses were analyzed for internal consistency using standardized Cronbach's alpha values within each of the five domains. A factor analysis was performed to confirm the domain structure of the questionnaire. RESULTS: Data from 486 MSM were analyzed. The factor analysis supported the domain structure described. Questions about erectile function, orgasmic function, and sexual desire performed well, with Cronbach's alpha values of 0.82, 0.83, and 0.89, respectively. Questions concerning intercourse satisfaction were less consistent (Cronbach's alpha 0.55) because frequency of attempts at sexual intercourse did not correlate with other responses. Responses about satisfaction with sex with a regular partner diverged from satisfaction with overall sex life. Frequency of morning erections diverged from other aspects of erectile function, whereas erections with masturbation correlated better. CONCLUSIONS: Internal consistency was high overall. This tool is suitable for HIV-positive MSM and can be used in screening, research, and monitoring treatment response.

A meta-analysis of transient elastography for the detection of hepatic fibrosis.

OBJECTIVES: The use of transient elastography to assess liver stiffness measurement (LSM) has now become widely available for the diagnosis of liver fibrosis as a rapid, noninvasive test (it is still not approved for use in the United States). It has previously been showed as an accurate method of representing the state of liver fibrosis with concomitant evaluation of liver biopsy and the histologic scoring system METAVIR. We performed a meta-analysis to further assess its use in comparison with liver biopsy. METHODS: Studies from the literature were analyzed with a median liver stiffness value in kilopascal given for fibrosis stages according to histopathologic findings on biopsy and best discriminant cutoff levels in kilopascals for significant fibrosis (>or=F2) and cirrhosis (F4). RESULTS: A total of 22 studies were selected comprising 4,430 patients; chronic hepatitis C infection was the most common etiology of fibrosis. The pooled estimates for significant fibrosis (>or=F2) measured 7.71 kPa (LSM cutoff value) with a sensitivity of 71.9% [95% confidence interval (CI): 71.4%-72.4%] and specificity of 82.4% (95% CI: 81.9-82.9%), whereas for cirrhosis (F4) the results showed a cutoff of 15.08 kPa with a sensitivity of 84.45% (95% CI: 84.2-84.7%) and specificity of 94.69% (95% CI: 94.3%-95%). CONCLUSIONS: Further evaluation of transient elastography to assess LSM is required in prospective studies to potentially increase the sensitivity and establish its clinical utility.

Pregnancy Gestation Impacts on HIV-1-Specific Granzyme B Response and Central Memory CD4 T Cells.

Pregnancy induces alterations in peripheral T-cell populations with both changes in subset frequencies and anti-viral responses found to alter with gestation. In HIV-1 positive women anti-HIV-1 responses are associated with transmission risk, however detailed investigation into both HIV-1-specific memory responses associated with HIV-1 control and T-cell subset changes during pregnancy have not been undertaken. In this study we aimed to define pregnancy and gestation related changes to HIV-1-specific responses and T-cell phenotype in ART treated HIV-1 positive pregnant women. Eleven non-pregnant and 24 pregnant HIV-1 positive women were recruited, peripheral blood samples taken, fresh cells isolated, and compared using ELISpot assays and flow cytometry analysis. Clinical data were collected as part of standard care, and non-parametric statistics used. Alterations in induced IFNγ, IL-2, IL-10, and granzyme B secretion by peripheral blood mononuclear cells in response to HIV-1 Gag and Nef peptide pools and changes in T-cell subsets between pregnant and non-pregnant women were assessed, with data correlated with participant clinical parameters and longitudinal analysis performed. Cross-sectional comparison identified decreased IL-10 Nef response in HIV-1 positive pregnant women compared to non-pregnant, while correlations exhibited reversed Gag and Nef cytokine and protease response associations between groups. Longitudinal analysis of pregnant participants demonstrated transient increases in Gag granzyme B response and in the central memory CD4 T-cell subset frequency during their second trimester, with a decrease in CD4 effector memory T cells from their second to third trimester. Gag and Nef HIV-1-specific responses diverge with pregnancy time-point, coinciding with relevant T-cell phenotype, and gestation associated immunological adaptations. Decreased IL-10 Nef and both increased granzyme B Gag response and central memory CD4 T cells implies that amplified antigen production is occurring, which suggests a period of compromised HIV-1 control in pregnancy.