Suchergebnisse

Purpose of the studyTo investigate the impact of ART, HIV viremia and immunosuppression on triglyceride (TG), total cholesterol (TC) and high density lipoprotein cholesterol (HDL‐C) levels.MethodsWe considered the cross‐sectional associations between TG, TC and HDL‐C (mmol/l; first available measurement on/after enrolment in the D:A:D study) and use of ART, HIV viral load (VL; copies/ml), and CD4 count (cells/mm3) measured at the same time. TG was log10 transformed to ensure normality. Analyses were performed using linear regression and adjusted for other factors known to impact lipid levels (table footnote). ART and VL status were combined (off ART&VL >100,000, off ART&VL <100,000, on ART&VL <500, on ART&VL >500), current and nadir CD4 count were categorised as <200, 200–349, 350–499 and >500.Summary of results44,322/49,734 participants in the D:A:D Study (89.1%) contributed a TG measurement (median; IQR 1.52; 1.00–2.45), 45,169 (90.8%) a TC measurement (4.80; 4.00–5.70) and 38,604 (77.6%) a HDL‐C measurement (1.12; 0.90–1.40). Most participants were male (74%), of white ethnicity (51%), without AIDS (78%), were not receiving lipid‐lowering drugs (4%) and were ART experienced (61%) with 47% previously exposed to PIs, 61% previously exposed to NRTIs and 29% previously exposed to NNRTIs. The median (IQR) age, current CD4 count and CD4 nadir were 38 (36–45) years, 400 (242–590) cells/µl and 240 (100–410) cells/µl respectively. Compared to those on ART with a suppressed VL, all lipids were lower for those off ART (Table); non‐suppressive ART was also associated with lower TC and HDL‐C levels (no impact on TG). A low current CD4 count was associated with lower lipid levels, whereas a low nadir CD4 count was associated with higher TC and TG levels. Prior AIDS diagnosis was associated with higher TG and TC, but lower HDL‐C levels.

Impact of ART, immunosuppression and viraemia, on TG, TC and HDL‐C (mmol/l)












Average impact on log10TG*†

Average inpact on TC*
Average impact on HDL‐C*




ART and VL


Off ART … VL≥100000
−0.09 (−0.10,−0.08)
<0.001
−0.55 (−0.60,−0.51)
<0.001
−0.14 (−0.16,−0.13)
<0.001


Off ART … VL<100000
−0.04 (−0.06,−0.03)
<0.001
−0.85 (−0.91,−0.78)
<0.001
−0.31 (−0.33,−0.29)
<0.001


On ART … VL<500
Ref

Ref

Ref



On ART … VL≥500
0.00 (−0.01, 0.00)
0.38
−0.40 (−0.44,−0.36)
<0.001
−0.16 (−0.17,−0.15)
<0.001


CD4 count


<200
−0.03 (−0.04,−0.02)
<0.001
−0.33 (−0.39,−0.28)
<0.001
−0.04 (−0.06,−0.02)
<0.001


200–349
−0.02 (−0.03,−0.01)
<0.001
−0.11 (−0.15,−0.06)
<0.001
0.00 (−0.01, 0.02)
0.72


350–499
Ref

Ref

Ref



500+
0.04 (0.03, 0.04)
<0.001
0.12 (0.08, 0.16)
<0.001
−0.02 (−0.03,−0.00)
0.02


Nadir CD4 Count


<200
0.07 (0.06, 0.08)
<0.001
0.19 (0.14, 0.24)
<0.001
−0.05 (−0.06,−0.03)
<0.001


200–349
0.02 (0.01, 0.03)
<0.001
0.01 (−0.03, 0.06)
0.57
−0.03 (−0.05,−0.02)
<0.001


350–499
Ref

Ref

Ref



500 +
0.00 (−0.02, 0.01)
0.33
0.03 (−0.02, 0.09)
0.23
0.04 (0.02, 0.06)
<0.001


Prior AIDS
0.05 (0.05, 0.06)
<0.001
0.11 (0.08, 0.15)
<0.001
−0.03 (−0.04,−0.01)
<0.001





estimates included are mutually adjusted for each other and for the following demographic variables: age; gender; mode of infection; ethnicity; body mass index; smoking; family history of CVD; diabetes; use of lipid lowering drugs; co‐infection with hepatitis C; participating cohort; and year of entry into study.
TG is log10 transformed. Thus, the results presented for TG reflect relative rather than absolute effects. For example, lipid levels for those off ART … VL ≥100000 are 9% lower than those on ART … VL < 500.

ConclusionAlthough specific drug classes were not considered, lipid levels are considerably higher in those on a suppressive ART regimen. The higher TC/TG and lower HDL‐C levels seen among those with low nadir CD4 count and with a prior AIDS diagnosis suggests severe immunosuppression may be associated with dyslipidaemia over the long‐term.

Background: Financial incentives and audit plus feedback on performance are two strategies commonly used by governments to motivate general practitioners (GP) to undertake specific healthcare activities. However, in recent years, governments have reduced or removed incentive payments without evidence of the potential impact on GP behaviour and patient outcomes. This trial (known as ACCEPt-able) aims to determine whether preventive care activities in general practice are sustained when financial incentives and/or external audit plus feedback on preventive care activities are removed. The activity investigated is annual chlamydia testing for 16- to 29-year-old adults, a key preventive health strategy within this age group. Methods/design: ACCEPt-able builds on a large cluster randomised controlled trial (RCT) that evaluated a 3-year chlamydia testing intervention in general practice. GPs were provided with a support package to facilitate annual chlamydia testing of all sexually active 16- to 29-year-old patients. This package included financial incentive payments to the GP for each chlamydia test conducted and external audit plus feedback on each GP's chlamydia testing rates. ACCEPt-able is a factorial cluster RCT in which general practices are randomised to one of four groups: (i) removal of audit plus feedback-continue to receive financial incentive payments for each chlamydia test; (ii) removal of financial incentive payments-continue to receive audit plus feedback; (iii) removal of financial incentive payments and audit plus feedback; and (iv) continue financial incentive payments and audit plus feedback. The primary outcome is chlamydia testing rate measured as the proportion of sexually active 16- to 29-year-olds who have a GP consultation within a 12-month period and at least one chlamydia test. Discussion: This will be the first RCT to examine the impact of removal of financial incentive payments and audit plus feedback on the chlamydia testing behaviour of GPs. This trial is particularly timely and will increase our understanding about the impact of financial incentives and audit plus feedback on GP behaviour when governments are looking for opportunities to control healthcare budgets and maximise clinical outcomes for money spent. The results of this trial will have implications for supporting preventive health measures beyond the content area of chlamydia. Trial registration: The trial has been registered on the Australian and New Zealand Clinical Trials Registry (ACTRN12614000595617).

© 2018 Elsevier Ltd Background: Screening young adults who are sexually active for genital Chlamydia trachomatis infection is promoted in several high-income countries, but its effectiveness at the population level is highly debated. We aimed to investigate the effects of opportunistic chlamydia testing in primary care on the estimated chlamydia prevalence in the population aged 16–29 years in Australia. Methods: We did a cluster-randomised controlled trial. Clusters were rural towns with a minimum of 500 women and men aged 16–29 years and no more than six primary care clinics. We randomly allocated each cluster using a computer-generated minimisation algorithm to receive a multifaceted, clinic-based chlamydia testing intervention or to continue usual care. The intervention included computerised reminders to test patients, an education package, payments for chlamydia testing, and feedback on testing rates. The primary outcome was chlamydia prevalence, estimated before randomisation (survey 1) and at the end of the trial (survey 2) in patients aged 16–29 years who attended the clinics. Analyses were done by intention to treat. General practitioners and clinic staff were aware of group allocation, whereas patients and laboratory staff who performed the chlamydia tests were not. This trial was completed on Dec 31, 2015, and is registered (ACTRN12610000297022). Findings: Between Dec 14, 2010, and Sept 14, 2015, 26 clusters (63 clinics) received the chlamydia testing intervention and 26 (67 clinics) continued usual care. Over a mean duration of 3·1 years (SD 0·3), 93 828 young adults attended intervention clinics and 86 527 attended control clinics. The estimated chlamydia prevalence decreased from 5·0% (95% CI 3·8 to 6·2) at survey 1 to 3·4% (2·7 to 4·1) at survey 2 in the intervention clusters (difference −1·6%, 95% CI −2·9 to −0·3) and from 4·6% (95% CI 3·5 to 5·7) at survey 1 to 3·4% (2·4 to 4·5) at survey 2 in the control clusters (difference −1·1%, −2·7 to 0·5). The unadjusted odds ratio for the difference between intervention and control clusters was 0·9 (95% CI 0·5 to 1·5). Interpretation: These findings, in conjunction with evidence about the feasibility of sustained uptake of opportunistic testing in primary care, indicate that sizeable reductions in chlamydia prevalence might not be achievable. Funding: Australian Government Department of Health, National Health and Medical Research Council, Victorian Department of Health and Human Services, and New South Wales Ministry of Health.

Background Several studies have shown that diabetes confers a higher relative risk of vascular mortality among women than among men, but whether this increased relative risk in women exists across age groups and within defined levels of other risk factors is uncertain. We aimed to determine whether differences in established risk factors, such as blood pressure, BMI, smoking, and cholesterol, explain the higher relative risks of vascular mortality among women than among men. Methods In our meta-analysis, we obtained individual participant-level data from studies included in the Prospective Studies Collaboration and the Asia Pacific Cohort Studies Collaboration that had obtained baseline information on age, sex, diabetes, total cholesterol, blood pressure, tobacco use, height, and weight. Data on causes of death were obtained from medical death certificates. We used Cox regression models to assess the relevance of diabetes (any type) to occlusive vascular mortality (ischaemic heart disease, ischaemic stroke, or other atherosclerotic deaths) by age, sex, and other major vascular risk factors, and to assess whether the associations of blood pressure, total cholesterol, and body-mass index (BMI) to occlusive vascular mortality are modified by diabetes. Results Individual participant-level data were analysed from 980 793 adults. During 9·8 million person-years of follow-up, among participants aged between 35 and 89 years, 19 686 (25·6%) of 76 965 deaths were attributed to occlusive vascular disease. After controlling for major vascular risk factors, diabetes roughly doubled occlusive vascular mortality risk among men (death rate ratio [RR] 2·10, 95% CI 1·97–2·24) and tripled risk among women (3·00, 2·71–3·33; χ2 test for heterogeneity p<0·0001). For both sexes combined, the occlusive vascular death RRs were higher in younger individuals (aged 35–59 years: 2·60, 2·30–2·94) than in older individuals (aged 70–89 years: 2·01, 1·85–2·19; p=0·0001 for trend across age groups), and, across age groups, the death RRs were higher among women than among men. Therefore, women aged 35–59 years had the highest death RR across all age and sex groups (5·55, 4·15–7·44). However, since underlying confounder-adjusted occlusive vascular mortality rates at any age were higher in men than in women, the adjusted absolute excess occlusive vascular mortality associated with diabetes was similar for men and women. At ages 35–59 years, the excess absolute risk was 0·05% (95% CI 0·03–0·07) per year in women compared with 0·08% (0·05–0·10) per year in men; the corresponding excess at ages 70–89 years was 1·08% (0·84–1·32) per year in women and 0·91% (0·77–1·05) per year in men. Total cholesterol, blood pressure, and BMI each showed continuous log-linear associations with occlusive vascular mortality that were similar among individuals with and without diabetes across both sexes. Interpretation Independent of other major vascular risk factors, diabetes substantially increased vascular risk in both men and women. Lifestyle changes to reduce smoking and obesity and use of cost-effective drugs that target major vascular risks (eg, statins and antihypertensive drugs) are important in both men and women with diabetes, but might not reduce the relative excess risk of occlusive vascular disease in women with diabetes, which remains unexplained. Funding UK Medical Research Council, British Heart Foundation, Cancer Research UK, European Union BIOMED programme, and National Institute on Aging (US National Institutes of Health).