Outcomes in patients waiting for antiretroviral treatment in the Free State Province, South Africa: prospective linkage study

Objective: In South Africa, many HIV-infected patients experience delays in accessing antiretroviral therapy (ART). We examined pretreatment mortality and access to treatment in patients waiting for ART. Design: Cohort of HIV-infected patients assessed for ART eligibility at 36 facilities participating in the Comprehensive HIV and AIDS Management (CHAM) program in the Free State Province. Methods: Proportion of patients initiating ART, pre-ART mortality and risk factors associated with these outcomes were estimated using competing risks survival analysis. Results: Forty-four thousand, eight hundred and forty-four patients enrolled in CHAM between May 2004 and December 2007, of whom 22 083 (49.2%) were eligible for ART; pre-ART mortality was 53.2 per 100 person-years [95% confidence interval (CI) 51.8–54.7]. Median CD4 cell count at eligibility increased from 87 cells/ml in 2004 to 101 cells/ml in 2007. Two years after eligibility an estimated 67.7% (67.1–68.4%) of patients had started ART, and 26.2% (25.6–26.9%) died before starting ART. Among patients with CD4 cell counts below 25 cells/ml at eligibility, 48% died before ART and 51% initiated ART. Men were less likely to start treatment and more likely to die than women. Patients in rural clinics or clinics with low staffing levels had lower rates of starting treatment and higher mortality compared with patients in urban/peri-urban clinics, or better staffed clinics. Conclusions: Mortality is high in eligible patients waiting for ART in the Free State Province. The most immunocompromised patients had the lowest probability of starting ART and the highest risk of pre-ART death. Prioritization of these patients should reduce waiting times and pre-ART mortality.

[Swiss clinical practice guidelines for skin cancer in organ transplant recipients]

Swiss clinical practice guidelines for skin cancer in organ transplant recipients Transplant patients have increased over the last decades. As a consequence of long-term immunosuppression, skin cancer, in particular squamous cell carcinoma (SCC), has become an important problem. Screening and education of potential organ transplant recipients (OTRs) regarding prevention of sun damage and early recognition of skin cancer are important before transplantation. Once transplanted, OTRs should be seen yearly by a dermatologist to ensure compliance with sun avoidance as well as for treatment of precancerosis and SCC. Early removal is the best treatment for SCC. Reduction of immunosuppression, switch to mTOR inhibitors and chemoprevention with acitretin may reduce the incidence of SCC. The dermatological follow-up of OTRs should be integrated into a comprehensive post-transplant management strategy.

Sustained impact of electronic alerts on rate of prophylaxis against venous thromboembolism

Advanced electronic alerts (eAlerts) and computerised physician order entry (CPOE) increase adequate thromboprophylaxis orders among hospitalised medical patients. It remains unclear whether eAlerts maintain their efficacy over time, after withdrawal of continuing medical education (CME) on eAlerts and on thromboprophylaxis indications from the study staff. We analysed 5,317 hospital cases from the University Hospital Zurich during 2006-2009: 1,854 cases from a medical ward with eAlerts (interventiongroup) and 3,463 cases from a surgical ward without eAlerts (controlgroup). In the intervention group, an eAlert with hospital-specific venous thromboembolism (VTE) prevention guidelines was issued in the electronic patient chart 6 hours after admission if no pharmacological or mechanical thromboprophylaxis had been ordered. Data were analysed for three phases: pre-implementation (phase 1), eAlert implementation with CME (phase 2), and post-implementation without CME (phase3). The rates of thromboprophylaxis in the intervention group were 43.4% in phase 1 and 66.7% in phase 2 (p<0.001), and increased further to 73.6% in phase3 (p=0.011). Early thromboprophylaxis orders within 12 hours after admission were more often placed in phase 2 and 3 as compared to phase 1 (67.1% vs. 52.1%, p<0.001). In the surgical control group, the thromboprophylaxis rates in the three phases were 88.6%, 90.7%, 90.6% (p=0.16). Advanced eAlerts may provide sustained efficacy over time, with stable rates of thromboprophylaxis orders among hospitalised medical patients.

Phosphatidylethanol (PEth) as a Biomarker of Alcohol Consumption in HIV-Positive Patients in Sub-Saharan Africa

Background:  Alcohol is heavily consumed in sub-Saharan Africa and affects HIV transmission and treatment and is difficult to measure. Our goal was to examine the test characteristics of a direct metabolite of alcohol consumption, phosphatidylethanol (PEth). Methods:  Persons infected with HIV were recruited from a large HIV clinic in southwestern Uganda. We conducted surveys and breath alcohol concentration (BRAC) testing at 21 daily home or drinking establishment visits, and blood was collected on day 21 (n = 77). PEth in whole blood was compared with prior 7-, 14-, and 21-day alcohol consumption. Results:  (i) The receiver operator characteristic area under the curve (ROC-AUC) was highest for PEth versus any consumption over the prior 21 days (0.92; 95% confidence interval [CI]: 0.86 to 0.97). The sensitivity for any detectable PEth was 88.0% (95% CI: 76.0 to 95.6) and the specificity was 88.5% (95% CI: 69.8 to 97.6). (ii) The ROC-AUC of PEth versus any 21-day alcohol consumption did not vary with age, body mass index, CD4 cell count, hepatitis B virus infection, and antiretroviral therapy status, but was higher for men compared with women (p = 0.03). (iii) PEth measurements were correlated with several measures of alcohol consumption, including number of drinking days in the prior 21 days (Spearman r = 0.74, p < 0.001) and BRAC (r = 0.75, p < 0.001). Conclusions:  The data add support to the body of evidence for PEth as a useful marker of alcohol consumption with high ROC-AUC, sensitivity, and specificity. Future studies should further address the period and level of alcohol consumption for which PEth is detectable.

Oestradiol enhances plasma growth hormone and insulin-like growth factor-I concentrations and increased the expression of their receptors mRNAs in the liver of ovariectomized cows

Many metabolic hormones, growth hormone (GH), insulin-like growth factor-I (IGF-I) and insulin affect ovarian functions. However, whether ovarian steroid hormones affect metabolic hormones in cattle remains unknown. This study aimed to determine the effect of sex steroids on the plasma profiles of GH, IGF-I and insulin and their receptors in the liver and adipose tissues of dairy cows. Ovariectomized cows (n = 14) were randomly divided into four groups: control group (n = 3) was treated with saline on Day 0; oestradiol (E2) group (n = 3), with saline and 1 mg oestradiol benzoate (EB) on Day 0 and 5, respectively; progesterone (P4) group (n = 4) with two CIDRs (Pfizer Inc., Tokyo, Japan) from Day 0; and E2 + P4 group (n = 4) with two CIDRs on Day 0 that were removed on Day 6 and were immediately injected with 1 mg EB. The animals were euthanized after the experiment, and liver and adipose tissues samples were quantitatively analysed using real-time PCR for the expression of mRNA for the GH (GHR), IGF-I (IGFR-I) and insulin (IR) receptor mRNAs. Oestradiol benzoate significantly increased the number of peaks (p < 0.05), pulse amplitude (p < 0.05) and area under the curve (AUC; p < 0.01) for plasma GH; moreover, it increased plasma IGF-I concentration (p < 0.05), but it had no effect on the plasma insulin profile. P4 significantly decreased the AUC (p < 0.01), compared with the control group, whereas it did not affect the number of peaks and the amplitude of GH pulses. P4 + E2 did not affect the GH pulse profile. E2 increased the mRNA expression of GHR, IGFR-I and IR in the liver (p < 0.05), whereas both P4 and E2 + P4 did not change their expressions. Our results provide evidence that the metabolic and reproductive endocrine axes may regulate each other to ensure optimal reproductive and metabolic function.

Variation in human platelet glycoprotein VI content modulates glycoprotein VI-specific prothrombinase activity

- Glycoprotein VI (GPVI) is a platelet-specific receptor for collagen that figures prominently in signal transduction. An addition to binding to type I and III collagens, GPVI is also bound specifically by collagen-related peptide and convulxin (CVX), a snake venom protein. We developed a quantitative assay of platelet GPVI in which biotin-conjugated CVX binds selectively to GPVI in separated total platelet proteins by a ligand blot procedure. Using this approach, we have documented a 5-fold range in platelet GPVI content among 23 normal healthy subjects. In addition, we have determined that CVX-induced or collagen-related peptide-induced prothrombinase activity is directly proportional to the platelet content of GPVI. A statistically significant correlation was observed at 2 CVX concentrations: 14.7 ng/mL (R(2)=0.854 and P<0.001, n=11) and 22 ng/mL (R(2)=0.776 and P<0.001, n=12). In previous studies, we established a similar range of expression of the integrin collagen receptor alpha(2)beta(1) on platelets of normal subjects. Among 15 donors, there is a direct correlation between platelet alpha(2)beta(1) density and GPVI content (R(2)=0.475 and P=0.004). In view of the well-documented association of GPVI with platelet procoagulant activity, this study suggests that the variation in GPVI content is a potential risk factor that may predispose individuals to hemorrhagic or thromboembolic disorders.

Direct and indirect effects of screening for Chlamydia trachomatis on the prevention of pelvic inflammatory disease: a mathematical modeling study

BACKGROUND Pelvic inflammatory disease (PID) results from the ascending spread of microorganisms, including Chlamydia trachomatis, to the upper genital tract. Screening could improve outcomes by identifying and treating chlamydial infections before they progress to PID (direct effect) or by reducing chlamydia transmission (indirect effect). METHODS We developed a compartmental model that represents a hypothetical heterosexual population and explicitly incorporates progression from chlamydia to clinical PID. Chlamydia screening was introduced, with coverage increasing each year for 10 years. We estimated the separate contributions of the direct and indirect effects of screening on PID cases prevented per 100,000 women. We explored the influence of varying the time point at which clinical PID could occur and of increasing the risk of PID after repeated chlamydial infections. RESULTS The probability of PID at baseline was 3.1% by age 25 years. After 5 years, the intervention scenario had prevented 187 PID cases per 100,000 women and after 10 years 956 PID cases per 100,000 women. At the start of screening, most PID cases were prevented by the direct effect. The indirect effect produced a small net increase in PID cases, which was outweighed by the effect of reduced chlamydia transmission after 2.2 years. The later that progression to PID occurs, the greater the contribution of the direct effect. Increasing the risk of PID with repeated chlamydial infection increases the number of PID cases prevented by screening. CONCLUSIONS This study shows the separate roles of direct and indirect PID prevention and potential harms, which cannot be demonstrated in observational studies.

Combined effect of soil bund with biological soil and water conservation measures in the northwestern Ethiopian highlands

Excessive runoff and soil erosion in the upper Blue Nile Basin poses a threat that has attracted the attention of the Ethiopian government because of the serious on-site effects in addition to downstream effects, such as the siltation of water harvesting structures and reservoirs. The objective of the study was to evaluate and recommend effective biophysical soil and water conservation measure(s) in the Debre Mewi watershed, about 30 km south of the Lake Tana. Six conservation measures were evaluated for their effects on runoff, soil loss, and forage yield using runoff plots. There was a significant difference between treatments for both runoff and soil loss. The four-year average annual soil loss in the different plots ranged from 26 to 71 t ha−1, and total runoff ranged from 180 to 302 mm, while annual rainfall varied between 854 mm in 2008 and 1247 mm in 2011. Soil bund combined with elephant grass had the lowest runoff and soil loss as compared to the other treatments, whereas the untreated control plot had the highest for both parameters. As an additional benefit, 2.8 and 0.7 t ha−1 year−1 of dried forage was obtained from elephant and local grasses, respectively. Furthermore, it was found that soil bund combined with Tephrosia increased soil organic matter by 13% compared to the control plot. Soil bund efficiency was significantly enhanced by combining them with biological measures and improved farmers’ perception of soil and water conservation measures.

The Career Engagement Scale: Development and validation of a measure of proactive career behaviors

Careers today increasingly require engagement in proactive career behaviors; however, there is a lack of validated measures assessing the general degree to which somebody is engaged in such career behaviors. We describe the results of six studies with six independent samples of German university students (total N = 2,854), working professionals (total N = 561), and university graduates (N = 141) that report the development and validation of the Career Engagement Scale - a measure of the degree of which somebody is proactively developing her or his career as expressed by diverse career behaviors. The studies provide supprt for measurement invariance across gender and time. In support of convergent and discriminant validity, we find that career engagement is more prevalent among working professionals than among university students and that this scale has incremental validity above several specific career behaviors regarding its relation to vocational identity clarity and career self-efficacy beliefs among students and to job and career satisfaction among employees. In support of incremental predictive validity, beyond the effects of several more specific careeer behaviors, career engagement while at university predicts higher job and career satisfaction several months later after beginning work.