A rapid review of antenatal hepatitis C virus testing in the United Kingdom.

BACKGROUND: The United Kingdom (UK) has committed to the World Health Organization's viral hepatitis elimination targets. New case finding strategies, such as antenatal testing, may be needed to achieve these targets. We conducted a rapid review to understand hepatitis C-specific antibody (anti-HCV) and HCV RNA test positivity in antenatal settings in the United Kingdom to inform guidance. METHODS: Articles and conference abstracts published between January 2000 and June 2022 reporting anti-HCV testing in antenatal settings were identified through PubMed and Web of Science searches. Results were synthesised using a narrative approach. RESULTS: The search identified 2,011 publications; 10 studies were included in the final synthesis. Seven studies used anonymous testing methods and three studies used universal opt-out testing. Anti-HCV test positivity ranged from 0.1 to 0.99%, with a median value of 0.38%. Five studies reported HCV RNA positivity, which ranged from 0.1 to 0.57% of the testing population, with a median value of 0.22%. One study reported cost effectiveness of HCV and found it to be cost effective at £9,139 per quality adjusted life years. CONCLUSION: The relative contribution of universal opt-out antenatal testing for HCV should be reconsidered, as antenatal testing could play an important role in new case-finding and aid achieving elimination targets.

Pharmacokinetics and pharmacodynamics of the novel monobactam LYS228 in a neutropenic murine thigh model of infection.

Objectives: The neutropenic murine thigh infection model and a dose-fractionation approach were used to determine the pharmacokinetic/pharmacodynamic (PK/PD) relationship of LYS228, a novel monobactam antibiotic with activity against Enterobacteriaceae including carbapenem-resistant strains. Methods: Mice (n = 4 per group) were inoculated with Enterobacteriaceae strains via intramuscular injection. Two hours post-bacterial inoculation, treatment with LYS228 was initiated. Animals were euthanized with CO2 24 h after the start of therapy and bacterial counts (log10 cfu) per thigh were determined. PK parameters were calculated using free (f) plasma drug levels. Results: Following a dose-fractionation study, non-linear regression analysis determined that the predominant PK/PD parameter associated with antibacterial efficacy of LYS228 was the percentage of the dosing interval that free drug concentrations remained above the MIC (%fT>MIC). In a dose-dependent manner, LYS228 reduced the thigh bacterial burden in models established with Enterobacteriaceae producing ß-lactamase enzymes of all classes (e.g. ESBLs, NDM-1, KPC, CMY-2 and OXA-48). The range of the calculated static dose was 86-649 mg/kg/day for the isolates tested, and the magnitude of the driver of efficacy was 37-83 %fT>MIC. %fT>MIC was confirmed as the parameter predominantly driving efficacy as evidenced by a strong coefficient of determination (r2 = 0.68). Neutrophils had minimal impact on the effect of LYS228 in the murine thigh infection model. Conclusions: LYS228 is efficacious in murine thigh infection models using ß-lactamase-producing strains of Enterobacteriaceae, including those expressing metallo-ß-lactamases, ESBLs and serine carbapenemases, with the PK/PD driver of efficacy identified as %T>MIC.

HIV coinfection among persons diagnosed with hepatitis B in England in 2008-2014.

OBJECTIVES: The aim of the study was to estimate HIV prevalence among persons with hepatitis B virus (HBV) infection in England and to examine associated risk factors. METHODS: Persons aged ≥ 15 years with an HBV surface antigen (HBsAg) test reported to Public Health England (PHE) sentinel surveillance during 2008-2014 were linked to the PHE national HIV/AIDS database. Coinfection was defined as an HIV diagnosis prior to, or within 6 months following, a positive HBsAg test. RESULTS: During 2008-2014, 2 149 933 persons were tested for HBsAg and 3.9% (1129 of 28 789) of HBsAg-positive persons were HIV positive. The probable route of HIV infection was heterosexual exposure for 95.3% of female patients and 32.3% of male patients, with 61.5% of male patients reporting sex between men. Among African-born coinfected persons, 84% probably acquired HIV there. Predictors of HIV positivity included older age [adjusted odds ratio (aOR) 1.1] and being of black ethnicity (aOR 15.5 for males; aOR 16.4 for females) or being male and of white ethnicity (aOR 8.2) compared with being female and of white ethnicity. HIV coinfection was more likely when HBV was diagnosed in sexual health (aOR 55.0), specialist liver (aOR 6.7), emergency department (aOR 5.3) and renal services (aOR 2.8) compared with general practice. Most (60.4%; 682 of 1129) coinfected persons were diagnosed with HIV infection > 6 months before HBV diagnosis. CONCLUSIONS: Persons testing positive for HBsAg had a low HIV infection rate and fell largely into two groups: those of black ethnicity with probable Africa-acquired infections and white men who have sex with men (MSM) with probable UK-acquired infections. Findings reinforce existing recommendations to sustain and improve both HBV testing of migrants from HBV-prevalent countries and vaccination among HIV-positive MSM. Findings also support blood-borne virus testing in sexual health services and emergency departments.

Trajectories of obesity by spousal diabetes status in the English Longitudinal Study of Ageing.

AIMS: To examine whether the development of obesity with age was different for individuals with and without a spouse with diabetes. METHODS: We analysed data from the English Longitudinal Study of Ageing [n= 7123, median (interquartile range) age 59 (53-67) years, 51% men], which included four clinical examination waves between 1998 and 2012. The main exposure was having a spouse with diabetes. Outcomes of interest were BMI and waist circumference. We fitted quadratic age-related trajectories using mixed-effect models stratified by sex and adjusted for education, smoking and the corresponding interaction terms between age and spousal diabetes status. RESULTS: The baseline spousal diabetes prevalence was 4.4%. Men with a wife with diabetes experienced a steeper increase in BMI (1.6 kg/m2 ) between ages 50 to 65 years than men with a wife without diabetes (0.9 kg/m2 ). Women with a husband with diabetes had a similarly shaped BMI trajectory to women with a husband without diabetes, but their average BMI levels were higher between ages 55 and 65 years. Waist circumference trajectories showed a similar shape by spousal diabetes status for men and women, although individuals with a spouse with diabetes had higher waist circumference values throughout follow-up. CONCLUSIONS: We found a positive association between spousal diabetes status and obesity development, which differed by sex among middle-aged individuals. Evidence from couple-based interventions is needed to test whether the latter could improve the current individual-focused public health strategies for obesity prevention.

Seroprevalence of HCV, HBV and HIV in two inner-city London emergency departments.

SUMMARY: In this paper we build on work investigating the feasibility of human immunodeficiency virus (HIV) testing in emergency departments (EDs), estimating the prevalence of hepatitis B, C and HIV infections among persons attending two inner-London EDs, identifying factors associated with testing positive in an ED. We also undertook molecular characterisation to look at the diversity of the viruses circulating in these individuals, and the presence of clinically significant mutations which impact on treatment and control.Blood-borne virus (BBV) testing in non-traditional settings is feasible, with emergency departments (ED) potentially effective at reaching vulnerable and underserved populations. We investigated the feasibility of BBV testing within two inner-London EDs. Residual samples from biochemistry for adults (⩾18 years) attending The Royal Free London Hospital (RFLH) or the University College London Hospital (UCLH) ED between January and June 2015 were tested for human immunodeficiency virus (HIV)Ag/Ab, anti-hepatitis C (HCV) and HBsAg. PCR and sequence analysis were conducted on reactive samples. Sero-prevalence among persons attending RFH and UCLH with residual samples (1287 and 1546), respectively, were 1.1% and 1.0% for HBsAg, 1.6% and 2.3% for anti-HCV, 0.9% and 1.6% for HCV RNA, and 1.3% and 2.2% for HIV. For RFH, HBsAg positivity was more likely among persons of black vs. white ethnicity (odds ratio 9.08; 95% confidence interval 2.72-30), with anti-HCV positivity less likely among females (0.15, 95% CI 0.04-0.50). For UCLH, HBsAg positivity was more likely among non-white ethnicity (13.34, 95% CI 2.20-80.86 (Asian); 8.03, 95% CI 1.12-57.61 (black); and 8.11, 95% CI 1.13-58.18 (other/mixed)). Anti-HCV positivity was more likely among 36-55 year olds vs. ⩾56 years (7.69, 95% CI 2.24-26.41), and less likely among females (0.24, 95% CI 0.09-0.65). Persons positive for HIV-markers were more likely to be of black vs. white ethnicity (4.51, 95% CI 1.63-12.45), and less likely to have one ED attendance (0.39, 95% CI 0.17-0.88), or female (0.12, 95% CI 0.04-0.42). These results indicate that BBV-testing in EDs is feasible, providing a basis for further studies to explore provider and patient acceptability, referral into care and cost-effectiveness.

Monitoring liver transplant rates in persons diagnosed with hepatitis C: a data linkage study, England 2008 to 2017.

IntroductionLiver transplantation is an important measure of burden from hepatitis C virus (HCV)-associated liver disease.AimsTo describe transplant rates and survival in individuals with HCV infection from 2008 to 2017 in England through data linkage.MethodsThis is a retrospective observational cohort study. Laboratory reports of HCV infection were linked to the Liver Transplant Registry for individuals aged 15 years and over, first diagnosed between 1998 and 2017. We estimated age-sex standardised incidence rates and used Poisson regression to investigate predictors of liver transplantation and test for a change in incidence after introduction of direct-acting antivirals (DAAs) in 2014. Kaplan-Meier survival analysis was used to calculate post-transplant survival rates.ResultsOf 124,238 individuals diagnosed with HCV infection, 1,480 were registered and 1,217 received a liver transplant. Of individuals registered, 1,395 had post-HCV cirrhosis and 636 had hepatocellular carcinoma (618 also had post-HCV cirrhosis). Median time from HCV diagnosis to transplant was 3.4 years (interquartile range: 1.3-6.8 years). Liver transplant rates were lower 2014-17 compared with 2011-13 (incidence rate ratio: 0.64; 95% confidence interval: 0.55-0.76). Survival rates were 93.4%, 79.9% and 67.9% at 1, 5 and 10 years, respectively. Data linkage showed minimal under-reporting of HCV in the transplant registry.ConclusionIn the post-DAA era, liver transplant rates have fallen in individuals with HCV infection, showing early impact of HCV treatment scale-up; but the short time from HCV diagnosis to liver transplant suggests late diagnosis is a problem.

Prevalence of diagnosed HIV infection among persons with hepatitis C virus infection: England, 2008-2014.

OBJECTIVES: In persons with hepatitis C virus (HCV) infection, HIV coinfection leads to faster progression to advanced liver disease. The aim of our study was to estimate diagnosed HIV prevalence among people with evidence of current HCV infection (polymerase chain reaction positive) and examine predictors of coinfection. METHODS: Adults (≥ 15 years old) with a current HCV infection reported to the Public Health England (PHE) sentinel surveillance of blood-borne viruses were linked to the PHE national HIV database using a deterministic methodology. Descriptive and multivariate analyses were conducted. RESULTS: Between 2008 and 2014, 5.0% (999/20 088) of adults with a current HCV infection were diagnosed with HIV coinfection. The majority acquired HIV through sex between men (441; 64.9%), followed by injecting drug use (153; 22.5%) and heterosexual contact (84; 12.4%). Of persons who were coinfected, 65.5% had been diagnosed with HIV infection > 6 months before their HCV diagnosis, 41.4% of whom had a negative anti-HCV test between their HIV and HCV diagnoses. In a multivariable model among persons with current HCV infection, an HIV diagnosis was more likely among men [adjusted odds ratio (aOR) 3.29; 95% confidence interval (CI) 2.60-4.16] and persons of black ethnicity (aOR 3.19; 95% CI 1.36-7.46), and less likely among older adults (aOR 0.85 per 10-year increase; 95% CI 0.79-0.92) and persons of Asian ethnicity (aOR 0.59; 95% CI 0.41-0.86). CONCLUSIONS: Our results indicate that the majority of diagnosed HIV and current HCV coinfections are among men who have sex with men. Safer sex campaigns should include awareness of transmission of HCV among MSM living with HIV.

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.

HIV incidence in the Estonian population in 2013 determined using the HIV-1 limiting antigen avidity assay.

OBJECTIVES: Estonia has one the highest number of new HIV diagnoses in the European Union, mainly among injecting drug users and heterosexuals. Little is known of HIV incidence, which is crucial for limiting the epidemic. Using a recent HIV infection testing algorithm (RITA) assay, we aimed to estimate HIV incidence in 2013. METHODS: All individuals aged ≥18 years newly-diagnosed with HIV in Estonia January- December 2013, except blood donors and those undergoing antenatal screening, were included. Demographic and clinical data were obtained from the Estonian Health Board and the Estonian HIV-positive patient database. Serum samples were tested for recent infection using the LAg-avidity EIA assay. HIV incidence was estimated based on previously published methods. RESULTS: Of 69,115 tested subjects, 286 (0.41%) were newly-diagnosed with HIV with median age of 33 years (IQR: 28-42) and 65% male. Self-reported routes of HIV transmission were mostly heterosexual contact (n = 157, 53%) and injecting drug use (n = 62, 21%); 64 (22%) were with unknown risk group. Eighty two (36%) were assigned recent, resulting in estimated HIV incidence of 0.06%, corresponding to 642 new infections in 2013 among the non-screened population. Incidence was highest (1.48%) among people who inject drugs. CONCLUSIONS: These high HIV incidence estimates in Estonia call for urgent action of renewed targeted public health promotion and HIV testing campaigns.

Establishing the cascade of care for hepatitis C in England-benchmarking to monitor impact of direct acting antivirals.

Little is known about engagement and retention in care of people diagnosed with chronic hepatitis C (HCV) in England. Establishing a cascade of care informs targeted interventions for improving case finding, referral, treatment uptake and retention in care. Using data from the sentinel surveillance of blood-borne virus (SSBBV) testing between 2005 and 2014, we investigate the continuum of care of those tested for HCV in England. Persons ≥1 year old with an anti-HCV test and subsequent RNA tests between 2005 and 2014 reported to SSBBV were collated. We describe the cascade of care, as the patient pathway from a diagnostic test, referral into care, treatment and patient outcomes. Between 2005 and 2014, 2 390 507 samples were tested for anti-HCV, corresponding to 1 766 515 persons. A total of 53 038 persons (35 190 men and 17 165 women) with anti-HCV positive were newly reported to SSBBV. An RNA test was conducted on 77.0% persons who were anti-HCV positive, 72.3% of whom were viraemic (RNA positive) during this time period, 21.4% had evidence of treatment and 3130 49.5% had evidence of a sustained virological response (SVR). In multivariable models, confirmation of viraemia by RNA test varied by age and region/test setting; evidence of treatment varied by age, year of test and region/test setting; and SVR varied by age, year of test and region/setting of test. In conclusion, our findings provide HCV cascade of care estimates prior to the introduction of direct acting antivirals. These findings provide important baseline cascade estimates to benchmark progress towards elimination of HCV as a major public health threat.

A global survey of HIV-positive people's attitudes towards cure research.

OBJECTIVES: Involvement of people living with HIV (PLHIV) in the design of HIV cure studies is important, given the potential risks to participants. We present results of an international survey of PLHIV to define these issues and inform cure research. METHODS: PLHIV were recruited in June-November 2014 through HIV websites, advocacy forums, social media and 12 UK HIV clinics. The survey included questions concerning demographics, HIV disease history, the desirability of types of cure and the patient's willingness to accept potential toxicity and treatment interruption (TI). We examined factors associated with TI and willingness to accept substantial risks. RESULTS: A total of 982 PLHIV completed the survey; 87% were male, 79% white and 81% men who have sex with men (MSM). Fifty-one per cent were aged 25-44 years and 69% were UK residents. The median time since diagnosis was 7 years [interquartile range (IQR) 2-17 years]. Eighty-eight per cent were receiving antiretrovirals (91% reported undetectable viral load). Health/wellbeing improvements (96%) and an inability to transmit HIV (90%) were more desirable cure characteristics than testing HIV-negative (69%). Ninety-five per cent were interested in participating in cure studies, and 59% were willing to accept substantial risks. PLHIV with a low CD4 count [201-350 cells/µL vs. ≥ 350 cells/µL; odds ratio (OR) 2.11; 95% confidence interval (CI) 1.11-4.00] were more likely to accept risks, whereas those with limited knowledge of HIV treatments vs. excellent/good knowledge and those aged ≥ 65 years vs. 45-64 years were less likely to accept risks [OR 0.58 (95% CI 0.37-0.90) and OR 0.18 (95% CI 0.07-0.45), respectively]. TI was acceptable for 62% of participants, with the main concerns being becoming unwell (82%), becoming infectious (76%) and HIV spreading through the body (76%). CONCLUSIONS: Cure research was highly acceptable to the PLHIV surveyed. Most individuals would accept risks, including TI, even in the absence of personal benefit. An optimal cure would improve health and minimize onward transmission risk.

Evaluation of hepatitis C testing in men who have sex with men, and associated risk behaviours, in Manchester, UK.

OBJECTIVE: To determine the prevalence of newly diagnosed hepatitis C virus (HCV) and associated risk behaviours among men who have sex with men (MSM) in Manchester. METHOD: A survey among MSM attending four genitourinary medicine clinics in Manchester was carried out over 9 months in 2013. Participants were asked about recent sexual behaviour, recreational drug use and HIV status. All men were offered an HCV test. RESULTS: Overall, 2030 MSM completed a questionnaire and accepted an HCV test. Of whom, 0.9% (18) were newly diagnosed with HCV, including 1.8% (13/735) of HIV-positive MSM, 0.7% (3/440) of MSM of unknown HIV status and 0.2% (2/855) of HIV-negative MSM. HCV positivity was significantly associated with HIV status (p<0.001). When compared with HIV-negative MSM, HIV-positive MSM had higher rates of sharing snorting drug equipment, injecting drugs/'slamming' and using recreational drugs (all p<0.05) but lower rates of five or more sexual partners and insertive unprotected anal intercourse (p<0.05). MSM newly diagnosed with HCV had significantly higher prevalence of unprotected sex, sex with someone HCV positive, fisting, group sex, ever injecting drugs/'slamming' and recreational drug use (p<0.002). CONCLUSIONS: In this survey, HIV-positive MSM had significantly different drug use behaviour which may explain the higher HCV burden. However, HCV was also associated with HIV-negative MSM engaging in high-risk sexual practices. All MSM attending sexual health clinics must have a risk assessment and HCV screening should be offered based on the risk. Further studies are warranted to explore the interplay between HCV and HIV risk associated with drug use versus sexual practices.

Cardiovascular risk factors and incident albuminuria in screen-detected type 2 diabetes.

BACKGROUND: It is unclear whether cardiovascular risk factor modification influences the development of renal disease in people with type 2 diabetes identified through screening. We determined predictors of albuminuria 5 years after a diagnosis of screen-detected diabetes within the ADDITION-Europe study, a pragmatic cardiovascular outcome trial of multifactorial cardiovascular risk management. METHODS: In 1826 participants with newly diagnosed, screen-detected diabetes without albuminuria, we explored associations between risk of new albuminuria (≥2.5 mg mmol-1 for males and ≥3.5 mg mmol-1 for females) and (1) baseline cardio-metabolic risk factors and (2) changes from baseline to 1 year in systolic blood pressure (ΔSBP) and glycated haemoglobin (ΔHbA1c ) using logistic regression. RESULTS: Albuminuria developed in 268 (15%) participants; baseline body mass index and active smoking were independently associated with new onset albuminuria in 5 years after detection of diabetes. In a model adjusted for age, gender, baseline HbA1c and blood pressure, a 1% decrease in HbA1c and 5-mm Hg decrease in SBP during the first year were independently associated with lower risks of albuminuria (odds ratio), 95% confidence interval: 0.76, 0.62 to 0.91 and 0.94, 0.88 to 1.01, respectively. Further adjustment did not materially change these estimates. There was no interaction between ΔSBP and ΔHbA1c in relation to albuminuria risk, suggesting likely additive effects on renal microvascular disease. CONCLUSIONS: Baseline measurements and changes in HbA1c and SBP a year after diagnosis of diabetes through screening independently associate with new onset albuminuria 4 years later. Established multifactorial treatment for diabetes applies to cases identified through screening.

Side-Effects and Social Norms Influencing Family Planning Use in Nepal.

Background Effective family planning (FP) programs promote modern contraceptives and help individuals achieve their reproductive goals. Despite Nepal's relatively high contraceptive prevalence rate (50%), 27% of married women have an unmet need for FP, and almost half of Nepalese women give birth by the age of 20. This formative study explored the factors that influence the use of contraceptives in Nepal. Objective To provide information about barriers to family planning use, general fertility awareness, and barriers to family planning use among difficult to reach groups communities. Method This qualitative study was implemented in five districts in Nepal. A total of 36 focus group discussions, 18 participatory group discussions, and 144 in-depth interviews were conducted. Participants included young married women, men and FP service providers in eight village development committees and two municipalities. The interviews were digitally recorded, transcribed in Nepali and then translated into English. Data was organized using Atlas Ti 7 and coded using a thematic analysis. Result Four key themes emerged from the analyses: 1) limited knowledge on fertility awareness and family planning methods, 2) religious-cultural factors including social norms impediments contraceptives use, 3) fear of side-effects, myths and misconceptions about modern contraceptives, and 4) structural barriers such as limited family planning services, and lack of same gender providers make it difficult for many women to access modern contraceptives services. Conclusion Continuing Nepal's recent gains in contraceptives prevalence rate will require strong educational interventions addressing fertility awareness, social norms around son preference, dispelling fear of side-effects while increasing the family planning method-mix. Health service providers should continue counseling clients on the management of potential side-effects and ensure accurate information about modern contraceptives.

Objectively measured sedentary time, physical activity and kidney function in people with recently diagnosed Type 2 diabetes: a prospective cohort analysis.

AIM: To assess the prospective association between objectively measured physical activity and kidney function over 4 years in people with Type 2 diabetes. METHODS: Individuals (120 women and 206 men) participating in the ADDITION-Plus trial underwent assessment of sedentary time (SED-time), time spent in moderate-to-vigorous-intensity physical activity (MVPA) and total physical activity energy expenditure (PAEE) using a combined heart rate and movement sensor, and kidney function [estimated glomerular filtration rate (eGFR), serum creatinine and urine albumin-to-creatinine ratio (ACR)] at baseline and after 4 years of follow-up. Multivariate regression was used to quantify the association between change in SED-time, MVPA and PAEE and kidney measures at four-year follow-up, adjusting for change in current smoking status, waist circumference, HbA1c , systolic blood pressure, triglycerides and medication usage. RESULTS: Over 4 years, there was a decline in eGFR values from 87.3 to 81.7 ml/min/1.73m(2) (P < 0.001); the prevalence of reduced eGFR (eGFR < 60 ml/min/1.73m(2) ) increased from 6.1 to 13.2% (P < 0.001). There were small increases in serum creatinine (median: 81-84 µmol/l, P < 0.001) and urine ACR (median: 0.9-1.0 mg/mmol, P = 0.005). Increases in SED-time were associated with increases in serum creatinine after adjustment for MVPA and cardiovascular risk factors (ß = 0.013, 95% CI: 0.001, 0.03). Conversely, increases in PAEE were associated with reductions in serum creatinine (ß = -0.001, 95% CI: -0.003, -0.0001). CONCLUSION: Reducing time spent sedentary and increasing overall physical activity may offer intervention opportunities to improve kidney function among individuals with diabetes. (Trial Registry no. ISRCTN 99175498).

Physical activity, sedentary time and gain in overall and central body fat: 7-year follow-up of the ProActive trial cohort.

OBJECTIVE: The objective of this study is to examine the independent associations of time spent in moderate-to-vigorous physical activity (MVPA) and sedentary (SED-time), with total and abdominal body fat (BF), and the bidirectionality of these associations in adults at high risk of type 2 diabetes. DESIGN AND SUBJECTS: We measured MVPA (min per day) and SED-time (h per day) by accelerometry, and indices of total (body weight, fat mass (FM), BF% and FM index) and abdominal BF (waist circumference (WC)) using standard procedures in 231 adults (41.3 ± 6.4 years) with parental history of type 2 diabetes (ProActive UK) at baseline, 1-year and 7-year follow-up. Mixed effects models were used to quantify the independent associations (expressed as standardised ß-coefficients (95% confidence interval (CI))) of MVPA and SED-time with fat indices, using data from all three time points. All models were adjusted for age, sex, intervention arm, monitor wear time, follow-up time, smoking status, socioeconomic status and MVPA/SED-time. RESULTS: MVPA was inversely and independently associated with all indices of total BF (for example, 1 s.d. higher MVPA was associated with a reduction in FM, ß = -0.09 (95% CI: -0.14, -0.04) s.d.) and abdominal BF (for example, WC: ß = -0.07 (-0.12, -0.02)). Similarly, higher fat indices were independently associated with a reduction in MVPA (for example, WC: ß = -0.25 (-0.36, -0.15); FM: ß = -0.27 (-0.36, -0.18)). SED-time was positively and independently associated with most fat indices (for example, WC: ß = 0.03 (-0.04, 0.09); FM: ß = 0.10 (0.03, 0.17)). Higher values of all fat indices independently predicted longer SED-time (for example, WC: ß = 0.10 (0.02, 0.18), FM: ß = 0.15 (0.07, 0.22)). CONCLUSIONS: The associations of MVPA and SED-time with total and abdominal BF are bidirectional and independent among individuals at high risk for type 2 diabetes. The association between BF and MVPA is stronger than the reciprocal association, highlighting the importance of considering BF as a determinant of decreasing activity and a potential consequence. Promoting more MVPA and less SED-time may reduce total and abdominal BF.

Are changes in glycaemic control associated with diabetes-specific quality of life and health status in screen-detected type 2 diabetes patients? Four-year follow up of the ADDITION-Cambridge cohort.

BACKGROUND: Interventions that improve HbA1c levels do not necessarily improve health-related quality of life (QoL). This issue may be particularly relevant in asymptomatic diabetes patients detected earlier in the course of the disease. METHODS: HbA1c , diabetes-specific QoL (ADDQoL) and health status were measured in 510 screen-detected diabetes patients from the ADDITION-Cambridge trial at 1 and 5 years post diagnosis. Multivariable logistic/linear regression was used to quantify the longitudinal association between change in HbA1c from 1 to 5 years and ADDQoL and health status at 5 years, adjusting for age, sex, education and trial group; alcohol consumption, smoking, physical activity, plasma vitamin C, HbA1c , ADDQoL or health status at 1 year, and glucose-lowering medication at 5 years. RESULTS: From 1 to 5 years, median HbA1c interquartile range increased from 6.3% (5.9-6.8) to 6.8% (6.4-7.4); the median ADDQoL score and mean health status physical health summary score decreased from -0.4 (-1 to -0.08) to -0.5 (-1.08 to -0.09) (suggesting an adverse impact of diabetes on QoL) and by -0.79 (8.94) points, respectively. Increases in HbA1c were independently associated with reporting a negative impact of diabetes on QoL (OR = 1.38, 95% CI: 1.03 to 1.85) but not with the health status summary scores. CONCLUSIONS: Increases in HbA1c from 1 to 5 years post-diagnosis were independently associated with increased odds of reporting a negative impact of diabetes on QoL. While our results suggest that efforts to reduce HbA1c do not adversely affect health-related QoL, large numbers of participants still report a negative impact of diabetes on their QoL 5 years post-diagnosis.

Cost-effectiveness of intensive multifactorial treatment compared with routine care for individuals with screen-detected Type 2 diabetes: analysis of the ADDITION-UK cluster-randomized controlled trial.

AIMS: To examine the short- and long-term cost-effectiveness of intensive multifactorial treatment compared with routine care among people with screen-detected Type 2 diabetes. METHODS: Cost-utility analysis in ADDITION-UK, a cluster-randomized controlled trial of early intensive treatment in people with screen-detected diabetes in 69 UK general practices. Unit treatment costs and utility decrement data were taken from published literature. Accumulated costs and quality-adjusted life years (QALYs) were calculated using ADDITION-UK data from 1 to 5 years (short-term analysis, n = 1024); trial data were extrapolated to 30 years using the UKPDS outcomes model (version 1.3) (long-term analysis; n = 999). All costs were transformed to the UK 2009/10 price level. RESULTS: Adjusted incremental costs to the NHS were £285, £935, £1190 and £1745 over a 1-, 5-, 10- and 30-year time horizon, respectively (discounted at 3.5%). Adjusted incremental QALYs were 0.0000, - 0.0040, 0.0140 and 0.0465 over the same time horizons. Point estimate incremental cost-effectiveness ratios (ICERs) suggested that the intervention was not cost-effective although the ratio improved over time: the ICER over 10 years was £82,250, falling to £37,500 over 30 years. The ICER fell below £30 000 only when the intervention cost was below £631 per patient: we estimated the cost at £981. CONCLUSION: Given conventional thresholds of cost-effectiveness, the intensive treatment delivered in ADDITION was not cost-effective compared with routine care for individuals with screen-detected diabetes in the UK. The intervention may be cost-effective if it can be delivered at reduced cost.

Healthy behaviours and 10-year incidence of diabetes: a population cohort study.

OBJECTIVE: To examine the association between meeting behavioural goals and diabetes incidence over 10 years in a large, representative Swedish population. METHODS: Population-based prospective cohort study of 32,120 individuals aged 35 to 55 years participating in a health promotion intervention in Västerbotten County, Sweden (1990 to 2013). Participants underwent an oral glucose tolerance test, clinical measures, and completed diet and activity questionnaires. Poisson regression quantified the association between achieving six behavioural goals at baseline - body mass index (BMI) <25 kg/m(2), moderate physical activity, non-smoker, fat intake <30% of energy, fibre intake ≥15 g/4184 kJ and alcohol intake ≤20 g/day - and diabetes incidence over 10 years. RESULTS: Median interquartile range (IQR) follow-up time was 9.9 (0.3) years; 2211 individuals (7%) developed diabetes. Only 4.4% of participants met all 6 goals (n=1245) and compared to these individuals, participants meeting 0/1 goals had a 3.74 times higher diabetes incidence (95% confidence interval (CI)=2.50 to 5.59), adjusting for sex, age, calendar period, education, family history of diabetes, history of myocardial infarction and long-term illness. If everyone achieved at least four behavioural goals, 14.1% (95% CI: 11.7 to 16.5%) of incident diabetes cases might be avoided. CONCLUSION: Interventions promoting the achievement of behavioural goals in the general population could significantly reduce diabetes incidence.

The impact of intensive multifactorial treatment on perceptions of chronic care among individuals with screen-detected diabetes: results from the ADDITION-Denmark trial.

OBJECTIVES: To describe perceptions of chronic care among diabetes patients 6 years after diagnosis by screening and to examine the impact of intensive treatment on patients' perceptions of chronic care. METHODS: The ADDITION-Denmark (2001-2006) trial compared the effects of intensive multifactorial therapy (IT) with routine care (RC) among individuals with screen-detected diabetes. Perceptions of chronic care were assessed using the Patient Assessment of Chronic Illness Care (PACIC) measure after 6-year follow-up (n = 937). Analysis was by intention-to-treat, accounting for clustering by general practice. RESULTS: The mean (SD) summary PACIC score was 2.4 (0.79) in the RC and 2.4 (0.82) in the IT group. The highest mean (SD) PACIC subscale score was for Delivery System Design/Decision Support [RC: 3.2 (0.95), IT: 3.3 (0.91)] and the lowest was for Follow-up/Coordination [RC: 2.1 (0.84), IT: 2.1 (0.87)]. Perceptions of chronic care did not differ between trial groups. CONCLUSIONS: Compared to RC, an intensive multifactorial intervention was not associated with differences in perceptions of chronic care among patients with screen-detected diabetes after 6 years. Intensive treatment does not adversely affect perceptions of chronic care early in the course of the disease. However, there is potentially room for improvement in some aspects of chronic care.