Dihydropteroate synthase mutations in Pneumocystis pneumonia: impact of applying different definitions of prophylaxis, mortality endpoints and mutant in a single cohort

Pneumocystis jirovecii dihydropteroate synthase (DHPS) gene mutations are well-reported. Although sulfa prophylaxis generally is associated with DHPS mutant infection, whether mutant infection is associated with poorer clinical outcomes is less clear. The differing definitions of sulfa prophylaxis and the different mortality endpoints used in these studies may be one explanation for the conflicting study results. Applying different definitions of prophylaxis, mortality endpoints and DHPS mutant to 301 HIV-infected patients with Pneumocystis pneumonia, we demonstrate that prophylaxis, irrespective of definition, increased the risk of infection with pure mutant (any prophylaxis: AOR 4.00, 95% CI: 1.83–8.76, p0.05). Future studies should standardize key variables associated with DHPS mutant infection as well as examine DHPS mutant subtypes (pure mutant vs. mixed infections) – perhaps even individual DHPS mutant genotypes – so that data can be pooled to better address this issue

Positive psychology/ Baumgardner

xxi, p. 238: ill., ind., tab.; 29 c

First Imaging of Coronal Mass Ejections in the Heliosphere Viewed from Outside the Sun Earth Line

We show for the first time images of solar coronal mass ejections (CMEs) viewed using the Heliospheric Imager (HI) instrument aboard the NASA STEREO spacecraft. The HI instruments are wide-angle imaging systems designed to detect CMEs in the heliosphere, in particular, for the first time, observing the propagation of such events along the Sun Earth line, that is, those directed towards Earth. At the time of writing the STEREO spacecraft are still close to the Earth and the full advantage of the HI dual-imaging has yet to be realised. However, even these early results show that despite severe technical challenges in their design and implementation, the HI instruments can successfully detect CMEs in the heliosphere, and this is an extremely important milestone for CME research. For the principal event being analysed here we demonstrate an ability to track a CME from the corona to over 40 degrees. The time altitude history shows a constant speed of ascent over at least the first 50 solar radii and some evidence for deceleration at distances of over 20 degrees. Comparisons of associated coronagraph data and the HI images show that the basic structure of the CME remains clearly intact as it propagates from the corona into the heliosphere. Extracting the CME signal requires a consideration of the F-coronal intensity distribution, which can be identified from the HI data. Thus we present the preliminary results on this measured F-coronal intensity and compare these to the modelled F-corona of Koutchmy and Lamy ( IAU Colloq. 85, 63, 1985). This analysis demonstrates that CME material some two orders of magnitude weaker than the F-corona can be detected; a specific example at 40 solar radii revealed CME intensities as low as 1.7×10[SUP]-14[/SUP] of the solar brightness. These observations herald a new era in CME research as we extend our capability for tracking, in particular, Earth-directed CMEs into the heliosphere

Two Years of the STEREO Heliospheric Imagers

Imaging of the heliosphere is a burgeoning area of research. As a result, it is awash with new results, using novel applications, and is demonstrating great potential for future research in a wide range of topical areas. The STEREO (Solar TErrestrial RElations Observatory) Heliospheric Imager (HI) instruments are at the heart of this new development, building on the pioneering observations of the SMEI (Solar Mass Ejection Imager) instrument aboard the Coriolis spacecraft. Other earlier heliospheric imaging systems have included ground-based interplanetary scintillation (IPS) facilities and the photometers on the Helios spacecraft. With the HI instruments, we now have routine wide-angle imaging of the inner heliosphere, from vantage points outside the Sun-Earth line. HI has been used to investigate the development of coronal mass ejections (CMEs) as they pass through the heliosphere to 1 AU and beyond. Synoptic mapping has also allowed us to see graphic illustrations of the nature of mass outflow as a function of distance from the Sun - in particular, stressing the complexity of the near-Sun solar wind. The instruments have also been used to image co-rotating interaction regions (CIRs), to study the interaction of comets with the solar wind and CMEs, and to witness the impact of CMEs and CIRs on planets. The very nature of this area of research - which brings together aspects of solar physics, space-environment physics, and solar-terrestrial physics - means that the research papers are spread among a wide range of journals from different disciplines. Thus, in this special issue, it is timely and appropriate to provide a review of the results of the first two years of the HI investigations

Dihydropteroate synthase mutations in Pneumocystis pneumonia: impact of applying different definitions of prophylaxis, mortality endpoints and mutant in a single cohort.

Pneumocystis jirovecii dihydropteroate synthase (DHPS) gene mutations are well-reported. Although sulfa prophylaxis generally is associated with DHPS mutant infection, whether mutant infection is associated with poorer clinical outcomes is less clear. The differing definitions of sulfa prophylaxis and the different mortality endpoints used in these studies may be one explanation for the conflicting study results. Applying different definitions of prophylaxis, mortality endpoints and DHPS mutant to 301 HIV-infected patients with Pneumocystis pneumonia, we demonstrate that prophylaxis, irrespective of definition, increased the risk of infection with pure mutant (any prophylaxis: AOR 4.00, 95% CI: 1.83-8.76, P < 0.001) but not mixed genotypes (any prophylaxis: AOR 0.78, 95% CI: 0.26-2.36, P = 0.65). However, infection with mutant DHPS, irrespective of definition, was not associated with increased mortality (all-cause or PCP death) at the three time-intervals examined (all P > 0.05). Future studies should standardize key variables associated with DHPS mutant infection as well as examine DHPS mutant subtypes (pure mutant vs. mixed infections) - perhaps even individual DHPS mutant genotypes - so that data can be pooled to better address this issue

Dihydropteroate synthase mutations in Pneumocystis pneumonia: impact of applying different definitions of prophylaxis, mortality endpoints and mutant in a single cohort.

Pneumocystis jirovecii dihydropteroate synthase (DHPS) gene mutations are well-reported. Although sulfa prophylaxis generally is associated with DHPS mutant infection, whether mutant infection is associated with poorer clinical outcomes is less clear. The differing definitions of sulfa prophylaxis and the different mortality endpoints used in these studies may be one explanation for the conflicting study results. Applying different definitions of prophylaxis, mortality endpoints and DHPS mutant to 301 HIV-infected patients with Pneumocystis pneumonia, we demonstrate that prophylaxis, irrespective of definition, increased the risk of infection with pure mutant (any prophylaxis: AOR 4.00, 95% CI: 1.83-8.76, P < 0.001) but not mixed genotypes (any prophylaxis: AOR 0.78, 95% CI: 0.26-2.36, P = 0.65). However, infection with mutant DHPS, irrespective of definition, was not associated with increased mortality (all-cause or PCP death) at the three time-intervals examined (all P > 0.05). Future studies should standardize key variables associated with DHPS mutant infection as well as examine DHPS mutant subtypes (pure mutant vs. mixed infections) - perhaps even individual DHPS mutant genotypes - so that data can be pooled to better address this issue

Long-Term Cigarette Smoking Trajectories Among HIV-Seropositive and Seronegative MSM in the Multicenter AIDS Cohort Study

OBJECTIVE: To examine the association between demographic characteristics and long-term smoking trajectory group membership among HIV-seropositive and HIV-seronegative men who have sex with men (MSM). METHODS: A cohort of 6,552 MSM from the Multicenter AIDS Cohort Study (MACS) were asked detailed information about their smoking history since their last follow-up. Group-based trajectory modeling was used to examine smoking behavior and identify trajectory group membership. Because participants enrolled after 2001 were more likely to be younger, HIV-seronegative, non-Hispanic black, and have a high school diploma or less, we also assessed time of enrollment in our analysis. RESULTS: Participants were grouped into 4 distinct smoking trajectory groups: persistent nonsmoker (n=3,737 [55.9%]), persistent light smoker (n=663 [11.0%]), heavy smoker to nonsmoker (n=531 [10.0%]), and persistent heavy smoker (n=1,604 [23.1%]). Compared with persistent nonsmokers, persistent heavy smokers were associated with being enrolled in 2001 and later (adjusted odds ratio [aOR], 2.35; 95% CI, 2.12-2.58), having a high school diploma or less (aOR, 3.22; 95% CI, 3.05-3.39), and being HIV-seropositive (aOR, 1.17; 95% CI, 1.01-1.34). These associations were statistically significant across all trajectory groups for time of enrollment and education but not for HIV serostatus. CONCLUSIONS: The overall decrease of smoking as shown by our trajectory groups is consistent with the national trend. Characteristics associated with smoking group trajectory membership should be considered in the development of targeted smoking cessation interventions among MSM and people living with HIV