Low HIV incidence in pregnant and postpartum women receiving a community-based combination HIV prevention intervention in a high HIV incidence setting in South Africa

BACKGROUND: Young Southern African women have the highest HIV incidence globally. Pregnancy doubles the risk of HIV acquisition further, and maternal HIV acquisition contributes significantly to the paediatric HIV burden. Little data on combination HIV prevention interventions during pregnancy and lactation are available. We measured HIV incidence amongst pregnant and postpartum women receiving a community-based combination HIV prevention intervention in a high HIV incidence setting in South Africa. METHODS: A cohort study that included HIV-uninfected pregnant women was performed. Lay community- based workers provided individualized HIV prevention counselling and performed three-monthly home and clinic-based individual and couples HIV testing. Male partners were referred for circumcision, sexually transmitted infections or HIV treatment as appropriate. Kaplan-Meier analyses and Cox's regression were used to estimate HIV incidence and factors associated with HIV acquisition. RESULTS The 1356 women included (median age 22.5 years) received 5289 HIV tests. Eleven new HIV infections were detected over 828.3 person-years (PY) of follow-up, with an HIV incidence rate of 1.33 infections/100 PY (95% CI: 0.74±2.40). Antenatally, the HIV incidence rate was 1.49 infections/100 PY (95% CI: 0.64±2.93) and postnatally the HIV incidence rate was 1.03 infections/100 PY (95% CI: 0.33±3.19). 53% of male partners received HIV testing and 66% of eligible partners received referral for circumcision. Women within known serodiscordant couples, and women with newly diagnosed HIV-infected partners, adjusted hazard ratio (aHR) = 32.7 (95% CI: 3.8±282.2) and aHR = 126.4 (95% CI: 33.8±472.2) had substantially increased HIV acquisition, respectively. Women with circumcised partners had a reduced risk of incident HIV infection, aHR = 0.22 (95% CI: 0.03±1.86). CONCLUSIONS: Maternal HIV incidence was substantially lower than previous regional studies. Community-based combination HIV prevention interventions may reduce high maternal HIV incidence in resource-poor settings. Expanded roll-out of home-based couples HIV testing and initiating pre-exposure prophylaxis for pregnant women within serodiscordant couples is needed in Southern Africa

Clinical, quality of life, and economic value of acromegaly disease control

Although acromegaly is a rare disease, the clinical, economic and health-related quality of life (HRQoL) burden is considerable due to the broad spectrum of comorbidities as well as the need for lifelong management. We performed a comprehensive literature review of the past 12 years (1998–2010) to determine the benefit of disease control (defined as a growth hormone [GH] concentration <2.5 μg/l and insulin-like growth factor [IGF]-1 normal for age) on clinical, HRQoL, and economic outcomes. Increased GH and IGF-1 levels and low frequency of somatostatin analogue use directly predicted increased mortality risk. Clinical outcome measures that may improve with disease control include joint articular cartilage thickness, vertebral fractures, left ventricular function, exercise capacity and endurance, lipid profile, and obstructive apnea events. Some evidence suggests an association between controlled disease and improved HRQoL. Total direct treatment costs were higher for patients with uncontrolled compared to controlled disease. Costs incurred for management of comorbidities, and indirect cost could further add to treatment costs. Optimizing disease control in patients with acromegaly appears to improve outcomes. Future studies need to evaluate clinical outcomes, as well as HRQoL and comprehensive economic outcomes achieved with controlled disease

Hypercoagulability in Cushing's syndrome: the role of specific haemostatic and fibrinolytic markers

OBJECTIVE: Hypercoagulability is a commonly described complication in patients with Cushing's syndrome. Recent clinical studies have indicated various abnormalities of coagulation and fibrinolysis parameters which may be related to that phenomenon. The aim of this study was to investigate the mechanisms underlying the hypercoagulable state in patients with Cushing's syndrome. ----- RESEARCH METHODS AND PROCEDURES: A wide range of serum markers involved in the processes of blood coagulation and fibrinolysis was measured in a group of 33 patients with Cushing's syndrome and 31 healthy controls. No participant was taking medication which could influence the result or had known diseases, except hypertension and diabetes, which could affect blood coagulation or fibrinolysis parameters. ----- RESULTS: Patients with Cushing's syndrome had higher levels of clotting factors II (P = 0.003), V (P < 0.001), VIII (P < 0.001), IX (P < 0.001), XI (P < 0.001) and XII (P = 0.019), protein C (P < 0.001), protein S (P < 0.001), C1-inhibitor (P < 0.001) and plasminogen activator inhibitor-1 (PAI-1) (P = 0.004). The activity of fibrinolytic markers, plasminogen (P < 0.001), antithrombin (P < 0.001) and antithrombin antigen (P = 0.001) was also increased in the patient group. ----- CONCLUSION: The study has demonstrated hypercoagulability in patients with Cushing's syndrome manifest as increased prothrombotic activity and compensatory activation of the fibrinolytic system. We propose the introduction of thromboprophylaxis in the preoperative and early postoperative periods, combined with a close follow-up in order to prevent possible thromboembolic events in patients with Cushing's syndrome

Low circulating IGF-I bioactivity is associated with human longevity: Findings in centenarians' offspring

Centenarians' offspring represent a suitable model to study age-dependent variables (e. g. IGF-I) potentially involved in the modulation of the lifespan. The aim of the present study was to investigate the role of the IGF-I in human longevity. We evaluated circulating IGF-I bioactivity measured by an innovative IGF-I Kinase Receptor Activation (KIRA) Assay, total IGF-I, IGFBP-3, total IGF-II, insulin, glucose, HOMA2-B% and HOMA2-S% in 192 centenarians' offspring and 80 offspring-controls of which both parents died relatively young. Both groups were well-matched for age, gender and BMI with the centenarians' offspring. IGF-I bioactivity (p<0.01), total IGF-I (p<0.01) and the IGF-I/IGFBP-3 molar ratio (p<0.001) were significantly lower in centenarians' offspring compared to offspring matched-controls. Serum insulin, glucose, HOMA2-B% and HOMA2-S% values were similar between both groups. In centenarians' offspring IGF-I bioactivity was inversely associated to insulin sensitivity. In conclusion: 1) centenarians' offspring had relatively lower circulating IGF-I bioactivity compared to offspring matched-controls; 2) IGF-I bioactivity in centenarians' offspring was inversely related to insulin sensitivity. These data support a role of the IGF-I/insulin system in the modulation of human aging process

New insight into the Hypercoagulability of Cushing's Syndrome

BACKGROUND: Hypercoagulability and a tendency for thromboembolic complications are reported in Cushing's syndrome (CS). The hypercoagulability is due mainly to the cortisol-induced increase in von Willebrand factor (VWF) and factor VIII. This is not a constant feature of CS, however; it depends on particular single nucleotide polymorphism (SNP) haplotypes in the VWF gene promoter: haplotype 1 (-3268G/-2709C/-2661A/-2527G) confers a greater risk of VWF upregulation by cortisol than haplotype 2 (-3268C/ -2709T/-2661G/-2527A). In healthy individuals these SNPs are in linkage disequilibrium with the -2144 (GT)(n) of the VWF promoter: haplotype 1 mainly segregates with short GT repeats (15-19, GTs), haplotype 2 with long repeats (GT 65 20, GT(L)). METHODS: We analyzed the (GT)(n) locus, the SNP haplotypes and their association with VWF levels in 80 CS patients in order to precisely define the cortisol-sensitive VWF promoter pattern. CS patients were divided into groups A (increased VWF) and B (normal VWF). RESULTS: Haplotype 1 and (GT)(S) were more frequent in group A patients, and conferred a 9- and 7.5-fold risk of developing high VWF levels, respectively. Haplotype 2 and (GT)(L) were more represented in group B. There was also an unexpected higher prevalence of recombinant SNP haplotypes in CS patients (6.2%) than in normals (0.9%), p = 0.002. CONCLUSIONS: Our results indicate that the cortisol-induced increase in VWF may be predicted by VWF promoter polymorphisms, haplotype 1 and (GT)(S) being the sensitive pattern. These represent new markers for defining the prothrombotic risk of CS. The clinical significance, if any, of the increased recombination rate in SNP haplotypes in the VWF promoter warrants further study