Demographics, Patterns of Care, and Survival in Pediatric Medulloblastoma

We evaluated the American College of Surgeon’s National Cancer Data Base (NCDB) to describe current hospital-based epidemiologic frequency, survival, and patterns of care of pediatric medulloblastoma. We analyzed NCDB 1998–2011 data on medulloblastoma for children ages 0–19 years using logistic and poisson regression, Kaplan–Meier survival estimates, and Cox proportional hazards models. 3647 cases of medulloblastoma in those aged 0–19 years were identified. Chemotherapy was received by 79 and 74% received radiation, with 65% receiving both therapies. Those who received radiation were more likely to be older than four, while those who received chemotherapy were more likely to be age four and younger. Variables associated with receipt of neither radiation nor chemotherapy included age at diagnosis of \u3c 1 year, female gender, being of race other than black or white, having no insurance, and living in a residential area with a low level of high school graduates. Better overall survival was observed as age at diagnosis increased, in females, and having received radiation. Compared to medulloblastoma, NOS, better survival was observed for those with demoplastic medulloblastoma, with worse survival in those with large cell medulloblastoma. Majority received multi- disciplinary therapy and radiation had the greatest effect on survival. Ages four and under were most likely to receive chemotherapy and least likely to receive radiation. Suboptimal treatment included 17.8% that did not receive chemotherapy, of which 11.8% received neither chemotherapy nor radiation. Disparities associated with medical access were characteristics for not receiving standard treatment, which resulted in poor outcome

The burden and characteristics of enteric fever at a healthcare facility in a densely populated area of Kathmandu

Enteric fever, caused by Salmonella enterica serovars Typhi and Paratyphi A (S. Typhi and S. Paratyphi A) remains a major public health problem in many settings. The disease is limited to locations with poor sanitation which facilitates the transmission of the infecting organisms. Efficacious and inexpensive vaccines are available for S. Typhi, yet are not commonly deployed to control the disease. Lack of vaccination is due partly to uncertainty of the disease burden arising from a paucity of epidemiological information in key locations. We have collected and analyzed data from 3,898 cases of blood culture-confirmed enteric fever from Patan Hospital in Lalitpur Sub-Metropolitan City (LSMC), between June 2005 and May 2009. Demographic data was available for a subset of these patients (n = 527) that were resident in LSMC and who were enrolled in trials. We show a considerable burden of enteric fever caused by S. Typhi (2,672; 68.5%) and S. Paratyphi A (1,226; 31.5%) at this Hospital over a four year period, which correlate with seasonal fluctuations in rainfall. We found that local population density was not related to incidence and we identified a focus of infections in the east of LSMC. With data from patients resident in LSMC we found that the median age of those with S. Typhi (16 years) was significantly less than S. Paratyphi A (20 years) and that males aged 15 to 25 were disproportionately infected. Our findings provide a snapshot into the epidemiological patterns of enteric fever in Kathmandu. The uneven distribution of enteric fever patients within the population suggests local variation in risk factors, such as contaminated drinking water. These findings are important for initiating a vaccination scheme and improvements in sanitation. We suggest any such intervention should be implemented throughout the LSMC area.This work was supported by The Wellcome Trust, Euston Road, London, United Kingdom. MFB is supported by the Medical Research Council (grant G0600718). SB is supported by an OAK foundation fellowship through Oxford University

Two nonrecombining sympatric forms of the human malaria parasite Plasmodium ovale occur globally.

BACKGROUND: Malaria in humans is caused by apicomplexan parasites belonging to 5 species of the genus Plasmodium. Infections with Plasmodium ovale are widely distributed but rarely investigated, and the resulting burden of disease is not known. Dimorphism in defined genes has led to P. ovale parasites being divided into classic and variant types. We hypothesized that these dimorphs represent distinct parasite species. METHODS: Multilocus sequence analysis of 6 genetic characters was carried out among 55 isolates from 12 African and 3 Asia-Pacific countries. RESULTS: Each genetic character displayed complete dimorphism and segregated perfectly between the 2 types. Both types were identified in samples from Ghana, Nigeria, São Tomé, Sierra Leone, and Uganda and have been described previously in Myanmar. Splitting of the 2 lineages is estimated to have occurred between 1.0 and 3.5 million years ago in hominid hosts. CONCLUSIONS: We propose that P. ovale comprises 2 nonrecombining species that are sympatric in Africa and Asia. We speculate on possible scenarios that could have led to this speciation. Furthermore, the relatively high frequency of imported cases of symptomatic P. ovale infection in the United Kingdom suggests that the morbidity caused by ovale malaria has been underestimated

Subtropical grass pollen allergens are important for allergic respiratory diseases in subtropical regions

Background: Grass pollen allergens are a major cause of allergic respiratory disease but traditionally prescribing practice for grass pollen allergen-specific immunotherapy has favoured pollen extracts of temperate grasses. Here we aim to compare allergy to subtropical and temperate grass pollens in patients with allergic rhinitis from a subtropical region of Australia. Methods. Sensitization to pollen extracts of the subtropical Bahia grass (Paspalum notatum), Johnson grass (Sorghum halepense) and Bermuda grass (Cynodon dactylon) as well as the temperate Ryegrass (Lolium perenne) were measured by skin prick in 233 subjects from Brisbane. Grass pollen-specific IgE reactivity was tested by ELISA and cross-inhibition ELISA. Results: Patients with grass pollen allergy from a subtropical region showed higher skin prick diameters with subtropical Bahia grass and Bermuda grass pollens than with Johnson grass and Ryegrass pollens. IgE reactivity was higher with pollen of Bahia grass than Bermuda grass, Johnson grass and Ryegrass. Patients showed asymmetric cross-inhibition of IgE reactivity with subtropical grass pollens that was not blocked by temperate grass pollen allergens indicating the presence of species-specific IgE binding sites of subtropical grass pollen allergens that are not represented in temperate grass pollens. Conclusions: Subtropical grass pollens are more important allergen sources than temperate grass pollens for patients from a subtropical region. Targeting allergen-specific immunotherapy to subtropical grass pollen allergens in patients with allergic rhinitis in subtropical regions could improve treatment efficacy thereby reducing the burden of allergic rhinitis and asthma

Targeting and killing of glioblastoma with activated T cells armed with bispecific antibodies

Abstract Background Since most glioblastomas express both wild-type EGFR and EGFRvIII as well as HER2/neu, they are excellent targets for activated T cells (ATC) armed with bispecific antibodies (BiAbs) that target EGFR and HER2. Methods ATC were generated from PBMC activated for 14 days with anti-CD3 monoclonal antibody in the presence of interleukin-2 and armed with chemically heteroconjugated anti-CD3×anti-HER2/neu (HER2Bi) and/or anti-CD3×anti-EGFR (EGFRBi). HER2Bi- and/or EGFRBi-armed ATC were examined for in vitro cytotoxicity using MTT and 51Cr-release assays against malignant glioma lines (U87MG, U118MG, and U251MG) and primary glioblastoma lines. Results EGFRBi-armed ATC killed up to 85% of U87, U118, and U251 targets at effector:target ratios (E:T) ranging from 1:1 to 25:1. Engagement of tumor by EGFRBi-armed ATC induced Th1 and Th2 cytokine secretion by armed ATC. HER2Bi-armed ATC exhibited comparable cytotoxicity against U118 and U251, but did not kill HER2-negative U87 cells. HER2Bi- or EGFRBi-armed ATC exhibited 50—80% cytotoxicity against four primary glioblastoma lines as well as a temozolomide (TMZ)-resistant variant of U251. Both CD133– and CD133+ subpopulations were killed by armed ATC. Targeting both HER2Bi and EGFRBi simultaneously showed enhanced efficacy than arming with a single BiAb. Armed ATC maintained effectiveness after irradiation and in the presence of TMZ at a therapeutic concentration and were capable of killing multiple targets. Conclusion High-grade gliomas are suitable for specific targeting by armed ATC. These data, together with additional animal studies, may provide the preclinical support for the use of armed ATC as a valuable addition to current treatment regimens

A Multi-Center Randomized Trial to Assess the Efficacy of Gatifloxacin versus Ciprofloxacin for the Treatment of Shigellosis in Vietnamese Children

The bacterial genus Shigella is the most common cause of dysentery (diarrhea containing blood and/or mucus) and the disease is common in developing countries with limitations in sanitation. Children are most at risk of infection and frequently require hospitalization and antimicrobial therapy. The WHO currently recommends the fluoroquinolone, ciprofloxacin, for the treatment of childhood Shigella infections. In recent years there has been a sharp increase in the number of organisms that exhibit resistance to nalidixic acid (an antimicrobial related to ciprofloxacin), corresponding with reduced susceptibility to ciprofloxacin. We hypothesized that infections with Shigella strains that demonstrate resistance to nalidixic acid may prevent effective treatment with ciprofloxacin. We performed a randomized controlled trial to compare 3 day ciprofloxacin therapy with 3 days of gatifloxacin, a newer generation fluoroquinolone with greater activity than ciprofloxacin. We measured treatment failure and time to the cessation of individual disease symptoms in 249 children with dysentery treated with gatifloxacin and 245 treated with ciprofloxacin. We could identify no significant differences in treatment failure between the two groups or in time to the cessation of individual symptoms. We conclude that, in Vietnam, ciprofloxacin and gatifloxacin are similarly effective for the treatment of acute dysentery

Omega-3 fatty acids in high-risk cardiovascular patients: a meta-analysis of randomized controlled trials

<p>Abstract</p> <p>Background</p> <p>Multiple randomized controlled trials (RCTs) have examined the cardiovascular effects of omega-3 fatty acids and have provided unexplained conflicting results. A meta-analysis of these RCTs to estimate efficacy and safety and potential sources of heterogeneity may be helpful.</p> <p>Methods</p> <p>The Cochrane library, MEDLINE, and EMBASE were systematically searched to identify all interventional trials of omega-3 fatty acids compared to placebo or usual diet in high-risk cardiovascular patients. The primary outcome was all-cause mortality and secondary outcomes were coronary restenosis following percutaneous coronary intervention and safety. Meta-analyses were carried out using Bayesian random-effects models, and heterogeneity was examined using meta-regression.</p> <p>Results</p> <p>A total of 29 RCTs (n = 35,144) met our inclusion criteria, with 25 reporting mortality and 14 reporting restenosis. Omega-3 fatty acids were not associated with a statistically significant decreased mortality (relative risk [RR] = 0.88, 95% Credible Interval [CrI] = 0.64, 1.03) or with restenosis prevention (RR = 0.89, 95% CrI = 0.72, 1.06), though the probability of some benefit remains high (0.93 and 0.90, respectively). However in meta-regressions, there was a >90% probability that larger studies and those with longer follow-up were associated with smaller benefits. No serious safety issues were identified.</p> <p>Conclusions</p> <p>Although not reaching conventional statistical significance, the evidence to date suggests that omega-3 fatty acids may result in a modest reduction in mortality and restenosis. However, caution must be exercised in interpreting these benefits as results were attenuated in higher quality studies, suggesting that bias may be at least partially responsible. Additional high quality studies are required to clarify the role of omega-3 fatty acid supplementation for the secondary prevention of cardiovascular disease.</p

A Bayesian approach for estimating typhoid fever incidence from large-scale facility-based passive surveillance data.

Funder: Public Health Research Programme; Id: http://dx.doi.org/10.13039/501100001921Decisions about typhoid fever prevention and control are based on estimates of typhoid incidence and their uncertainty. Lack of specific clinical diagnostic criteria, poorly sensitive diagnostic tests, and scarcity of accurate and complete datasets contribute to difficulties in calculating age-specific population-level typhoid incidence. Using data from the Strategic Typhoid Alliance across Africa and Asia program, we integrated demographic censuses, healthcare utilization surveys, facility-based surveillance, and serological surveillance from Malawi, Nepal, and Bangladesh to account for under-detection of cases. We developed a Bayesian approach that adjusts the count of reported blood-culture-positive cases for blood culture detection, blood culture collection, and healthcare seeking-and how these factors vary by age-while combining information from prior published studies. We validated the model using simulated data. The ratio of observed to adjusted incidence rates was 7.7 (95% credible interval [CrI]: 6.0-12.4) in Malawi, 14.4 (95% CrI: 9.3-24.9) in Nepal, and 7.0 (95% CrI: 5.6-9.2) in Bangladesh. The probability of blood culture collection led to the largest adjustment in Malawi, while the probability of seeking healthcare contributed the most in Nepal and Bangladesh; adjustment factors varied by age. Adjusted incidence rates were within or below the seroincidence rate limits of typhoid infection. Estimates of blood-culture-confirmed typhoid fever without these adjustments results in considerable underestimation of the true incidence of typhoid fever. Our approach allows each phase of the reporting process to be synthesized to estimate the adjusted incidence of typhoid fever while correctly characterizing uncertainty, which can inform decision-making for typhoid prevention and control