Clinical spectrum and severity of hemolytic anemia in glucose 6-phosphate dehydrogenase-deficient children receiving dapsone

Drug-induced acute hemolytic anemia led to the discovery of G6PD deficiency. However, most clinical data are from isolated case reports. In 2 clinical trials of antimalarial preparations containing dapsone (4,4′-diaminodiphenylsulfone; 2.5 mg/kg once daily for 3 days), 95 G6PD-deficient hemizygous boys, 24 G6PD-deficient homozygous girls, and 200 girls heterozygous for G6PD deficiency received this agent. In the first 2 groups, there was a maximum decrease in hemoglobin averaging -2.64 g/dL (range -6.70 to +0.30 g/dL), which was significantly greater than for the comparator group receiving artemether-lumefantrine (adjusted difference -1.46 g/dL; 95% confidence interval -1.76, -1.15). Hemoglobin concentrations were decreased by ≥ 40% versus pretreatment in 24/119 (20.2%) of the G6PD-deficient children; 13/119 (10.9%) required blood transfusion. In the heterozygous girls, the mean maximum decrease in hemoglobin was -1.83 g/dL (range +0.90 to -5.20 g/dL); 1 in 200 (0.5%) required blood transfusion. All children eventually recovered. All the G6PD-deficient children had the G6PD A- variant, ie, mutations V68MandN126D. Drug-induced acutehemolytic anemia in G6PD A- subjects can be life-threatening, depending on the nature and dosage of the drug trigger. Therefore, contrary to current perception, in clinical terms the A- type of G6PD deficiency cannot be regarded as mild. This study is registered at http://www.clinicaltrials.gov as NCT00344006 and NCT00371735. © 2012 by The American Society of Hematology

Clinical spectrum and severity of hemolytic anemia in glucose 6-phosphate dehydrogenase-deficient children receiving dapsone

Drug-induced acute hemolytic anemia led to the discovery of G6PD deficiency. However, most clinical data are from isolated case reports. In 2 clinical trials of antimalarial preparations containing dapsone (4,4′-diaminodiphenylsulfone; 2.5 mg/kg once daily for 3 days), 95 G6PD-deficient hemizygous boys, 24 G6PD-deficient homozygous girls, and 200 girls heterozygous for G6PD deficiency received this agent. In the first 2 groups, there was a maximum decrease in hemoglobin averaging -2.64 g/dL (range -6.70 to +0.30 g/dL), which was significantly greater than for the comparator group receiving artemether-lumefantrine (adjusted difference -1.46 g/dL; 95% confidence interval -1.76, -1.15). Hemoglobin concentrations were decreased by ≥ 40% versus pretreatment in 24/119 (20.2%) of the G6PD-deficient children; 13/119 (10.9%) required blood transfusion. In the heterozygous girls, the mean maximum decrease in hemoglobin was -1.83 g/dL (range +0.90 to -5.20 g/dL); 1 in 200 (0.5%) required blood transfusion. All children eventually recovered. All the G6PD-deficient children had the G6PD A- variant, ie, mutations V68MandN126D. Drug-induced acutehemolytic anemia in G6PD A- subjects can be life-threatening, depending on the nature and dosage of the drug trigger. Therefore, contrary to current perception, in clinical terms the A- type of G6PD deficiency cannot be regarded as mild. This study is registered at http://www.clinicaltrials.gov as NCT00344006 and NCT00371735. © 2012 by The American Society of Hematology

Evaluation of Mental Health First Aid from the Perspective Of Workplace End UseRs—EMPOWER: protocol of cluster randomised trial phase

Background: Mental Health First Aid (MHFA) is a mental health intervention that teaches people how to identify, understand and help someone who may be experiencing a mental health issue. Reviews of the implementation of MHFA found between 68 and 88% of trained Mental Health First Aiders had used their skills when in contact with someone experiencing mental health difficulties. Reviews evaluating the impact of MHFA suggest positive outcomes. However, to date, there has been no systematic, rigorous evaluation of the impact of MHFA on recipients of the intervention, the organisations providing it and the cost-effectiveness of MHFA overall. This trial will evaluate the effectiveness and cost-effectiveness of MHFA. Methods: The study is a multi-centred, two-arm clustered randomised controlled trial. Organisations will be randomly allocated to the control or intervention (estimated sample size 800 recipients). The intervention is the standard MHFA intervention provided by Mental Health First Aid England (MHFAE). The control condition will be organisations having a brief consultation from MHFAE on promoting mental health and well-being in the workplace. The primary outcome is health seeking behaviour, measured using the Actual Help Seeking Questionnaire, at 6 months’ follow-up. Data collection will be undertaken at baseline (T0), post-intervention—up to 3 months (T1), at 6 months (T2), 12 months (T3) and 24 months (T4). The primary analysis will be conducted on those participants who receive MHFA, a per protocol analysis. Discussion: The study is the first to evaluate the effect of MHFA in the workplace on employees with direct and indirect experience of the intervention, when compared with usual practice. Being also the first to assess, systematically, the social impact of MHFA and investigate its cost-effectiveness adds to the originality of the study. The study promises to yield important data, as yet unknown, regarding the effectiveness, cost-effectiveness, implementation issues, and the sustainability of MHFA in the workplace

The association between failed quit attempts and increased levels of psychological distress in smokers in a large New Zealand cohort

<p>Abstract</p> <p>Background</p> <p>Although the association between smoking status and poorer mental health has been well documented, the association between quit status and psychological distress is less clear. The aim of the present study is to investigate the association of smoking status and quit status with psychological distress.</p> <p>Methods</p> <p>Data for this study is from a single year of the Survey of Families, Income and Employment (SoFIE) conducted in New Zealand (2004/05) (n = 18,525 respondents). Smoking status and quit status were treated as exposure variables, and psychological distress (Kessler-10) was treated as the outcome variable. Logistic regression analyses were performed to determine the association of smoking with psychological distress in the whole adult population and quit status with psychological distress in the ex- and current-smoking population.</p> <p>Results</p> <p>Current smokers had higher rates of high and very high psychological distress compared to never smokers (adjusted odds ratio (aOR) = 1.45; 95% CI: 1.24-1.69). Unsuccessful quitters had much higher levels of high to very high levels of psychological distress (16%) than any other group. Moreover, compared to long-term ex-smokers, unsuccessful quitters had a much higher odds of high to very high levels of psychological distress (aOR = 1.73; 95% CI: 1.36-2.21).</p> <p>Conclusion</p> <p>These findings suggest that the significant association between smoking and psychological distress might be partly explained by increased levels of psychological distress among current smokers who made a quit attempt in the last year. This issue needs further study as it has implications for optimising the design of quitting support.</p

Activation of adherent vascular neutrophils in the lung during acute endotoxemia

BACKGROUND: Neutrophils constitute the first line of defense against invading microorganisms. Whereas these cells readily undergo apoptosis under homeostatic conditions, their survival is prolonged during inflammatory reactions and they become biochemically and functionally activated. In the present study, we analyzed the effects of acute endotoxemia on the response of a unique subpopulation of neutrophils tightly adhered to the lung vasculature. METHODS: Rats were treated with 5 mg/kg lipopolysaccharide (i.v.) to induce acute endotoxemia. Adherent neutrophils were isolated from the lung vasculature by collagenase digestion and sequential filtering. Agarose gel electrophoresis, RT-PCR, western blotting and electrophoretic mobility shift assays were used to evaluate neutrophil activity. RESULTS: Adherent vascular neutrophils isolated from endotoxemic animals exhibited decreased apoptosis when compared to cells from control animals. This was associated with a marked increase in expression of the anti-apoptotic protein, Mcl-1. Cells isolated 0.5–2 hours after endotoxin administration were more chemotactic than cells from control animals and expressed increased tumor necrosis factor-alpha and cyclooxygenase-2 mRNA and protein, demonstrating that they are functionally activated. Endotoxin treatment of the animals also induced p38 and p44/42 mitogen activated protein kinases in the adherent lung neutrophils, as well as nuclear binding activity of the transcription factors, NF-κB and cAMP response element binding protein. CONCLUSION: These data demonstrate that adherent vascular lung neutrophils are highly responsive to endotoxin and that pathways regulating apoptosis and cellular activation are upregulated in these cells

Isolation of Trypanosoma brucei gambiense from Cured and Relapsed Sleeping Sickness Patients and Adaptation to Laboratory Mice

Human African trypanosomiasis, or sleeping sickness, is still a major public health problem in central Africa. Melarsoprol is widely used for treatment of patients where the parasite has already reached the brain. In some regions in Angola, Sudan, Uganda and Democratic Republic of the Congo, up to half of the patients cannot be cured with melarsoprol. From previous investigations it is not yet clear what causes these high relapse rates. Therefore we aimed to establish a parasite collection isolated from cured as well as relapsed patients for downstream comparative drug sensitivity profiling. From 360 sleeping sickness patients, blood and cerebrospinal fluid (CSF) was collected before treatment and along the prescribed 24 months follow-up. Blood and CSF were inoculated in thicket rats (Grammomys surdaster), Natal multimammate mice (Mastomys natalensis) and immunodeficient laboratory mice (Mus musculus). Thus, we established a unique collection of Trypanosoma brucei gambiense type I parasites, isolated in the same disease focus and within a limited period, including 12 matched strains isolated from the same patient before treatment and after relapse. This collection is now available for genotypic and phenotypic characterisation to investigate the mechanism behind abnormally high treatment failure rates in Mbuji-Mayi, Democratic Republic of the Congo

A within-person theoretical perspective in sales research: outlining recommendations for adoption and consideration of boundary conditions

In the sales literature it is standard practice for researchers to collect cross-sectional data from multiple salespeople, and to compare those salespeople on the data obtained. This between-person approach is suitable for research aiming to draw conclusions between salespeople. However, many salesperson processes are dynamic and vary within salespeople over time, requiring datasets with repeated-measures. This article highlights the need to adopt a within-person theoretical perspective in sales research. Critically, the article shows how our present understanding of boundary conditions may change depending on whether a between-person or within-person level of analysis is adopted. Using examples from the sales literature, we show how the practical implications from between-persons research designs do not necessarily generalize to the within-person level. Further, we explain the methodological and analytical considerations that researchers must account for when undertaking within-person research. Furthermore, the article provides decision criteria that help to identify when within-person analysis should be conducted, outlining analysis tools that are capable of correctly estimating within-person effects without bias. Examples of how within-person research can enhance theory within future sales research, and how within-person research may influence management implications are also discussed. Finally, potential remedies to within-person research barriers are given

Mars Express and Trace Gas Orbiter – status, science highlights, plans

Mars Express With almost two decades of Mars observation behind it, Mars Express remains a dependable and highly productive mission. Recent science highlights include (1) continued mapping of subsurface reflectors beneath the south polar layered ice deposits, and associated work to explain the cause of these reflections; (2) a global map of minerals on Mars with 200 m/px resolution, obtained from analysis of infrared spectra; (3) release of 50 m resolution Digital Elevation Models based on HRSC stereo topography for quadrangles covering an ever-increasing proportion of the global surface; (4) detailed characterization of the landing sites of the ESA, NASA and Chinese rovers; (5) a global climatology of ozone and water from both nadir and occultation observations and its relation to atmospheric dust; (6) transient atmospheric phenomena, such as a recurrent orographic cloud feature at Arsia Mons; (7) detailed investigation of the ionospheric structure, its variability, and coupling to the lower atmosphere; (8) continued monitoring of both the upstream solar wind conditions and of downstream escaping ions; (9) detailed study of Phobos during flybys at altitudes as low as 50 km. Spacecraft and instrument teams continue to implement new and improved observation modes. One example is new MARSIS instrument software which now allows raw data to be returned from much longer subsurface sounding passes, improving the search for basal reflectors beneath polar ice caps; another example is mutual radio occultation observations between Mars Express and ExoMars Trace Gas Orbiter, potentially providing vertical profiles of ionospheric electron content with good spatial and temporal coverage. ExoMars Trace Gas Orbiter TGO has now completed two full Martian years of observations. Highlights include (1) continuing non-detection of methane, with upper limits as low as 20 ppt by volume. Reconciling this continued non-detection by TGO with the background levels of several hundred ppt in Gale crater by MSL remains an enigma, stimulating further research. (2) detection of HCl, the first reported halogen-containing species in the atmosphere of Mars. (3) further detail of the transport of water to high altitudes, a critical step in the escape of water from Mars. (4) mapping of atomic hydrogen in the top 1-2 m of regolith, indicative of water ice and hydrated minerals, suggesting surprisingly high abundances of subsurface water ice in low latitude regions including one in central Valles Marineris; and (5) continued acquisition of 5 m colour imagery and digital elevation models over a wide range of terrain and target types, including landing site characterization. Future plans: Mission extension cases for both missions have been submitted for the years 2023-2025 and 2026-2028. The extension of the observations would allow several new and optimized observation types; in particular, it will allow many collaborative observation opportunities with other missions and with ground- and space-based observatories. Of particular note are joint observations with James Webb Space Telescope, for which dedicated observations of Mars are due to be conducted in 2022-2023. Science goals include mapping of the water D/H ratio, search for trace gases including methane, and mapping of thermospheric structure using 4.3 μm CO2 emission; the full-disk views provided by JWST are highly complementary to the vertical profiling and long temporal coverage provided by MEx and TGO