Personalized Massive Open Online Course for Childhood Cancer Survivors: Behind the Scenes

Background  Today, in France, it is estimated that 1 in 850 people aged between 20 and 45 years has been treated for childhood cancer, which equals 40,000 to 50,000 people. As late effects of the cancer and its treatment affect a large number of childhood cancer survivors (CCS) and only 30% of them benefit from an efficient long-term follow-up care for prevention, early detection, and treatment of late effects, health education of CCS represents a challenge of public health. Objectives  Massive open online courses (MOOCs) are a recent innovative addition to the online learning landscape. This entertaining and practical tool could easily allow a deployment at a national level and make reliable information available for all the CCS in the country, wherever they live. Methods  The MOOC team brings together a large range of specialists involved in the long-term follow-up care, but also associations of CCS, video producers, a communication consultant, a pedagogical designer, a cartoonist and a musician. We have designed three modules addressing transversal issues (lifestyle, importance of psychological support, risks of fertility problems) and eight modules covering organ-specific problems. Detailed data on childhood cancer treatments received were used to allocate the specific modules to each participant. Results  This paper presents the design of the MOOC entitled “Childhood Cancer, Living Well, After,” and how its feasibility and its impact on CCS knowledge will be measured. The MOOC about long-term follow-up after childhood cancer, divided into 11 modules, involved 130 participants in its process, and resulted in a 170-minute film. The feasibility study included 98 CCS (31 males vs. 67 females; p  < 0.0001). Conclusion  Such personalized, free, and online courses with an online forum and a possible psychologist consultation based on unique characteristics and needs of each survivor population could improve adherence to long-term follow-up without alarming them unnecessarily.     

Clinical outcome of patients with HIV-1 infection according to immunologic and virologic response after 6 months of highly active antiretroviral therapy

BACKGROUND: The prognostic value of discordant immunologic (CD4 cell increase) and virologic (plasma HIV RNA level decrease) responses to antiretroviral treatment is not known. OBJECTIVE: To study the relation between clinical outcome of HIV-infected patients receiving highly active antiretroviral therapy (HAART) and early immunologic and virologic responses to such therapy. DESIGN: Prospective cohort study. SETTING: 68 hospitals in France. PATIENTS: 2236 protease inhibitor-naive patients. INTERVENTION: Initiation of HAART with one protease inhibitor and two nucleoside analogues between July 1996 and March 1997. MEASUREMENTS: Immunologic and virologic response at 6 months. Multivariate Cox models were used to assess the relation between these responses and progression to a new AIDS-defining event or death. RESULTS: On the basis of 6-month immunologic and virologic responses, patients were classified into four groups: complete response (47.5%), complete nonresponse (16.2%), immunologic response only (19.0%), and virologic response only (17.3%). After month 6 and within a median of 18 months, 69 patients died and 123 experienced a new AIDS-defining event. After adjustment, complete nonresponders and those with only a virologic response had significantly higher risks for clinical progression at 6 months (relative risk, 3.38 [95% CI, 2.28 to 5.02] and 1.98 [CI, 1.26 to 3.10], respectively) than complete responders. The difference between complete responders and those with only an immunologic response at 6 months was weaker and nonsignificant (relative risk, 1.55 [CI, 0.96 to 2.50]). CONCLUSIONS: Immunologic response after 6 months of HAART indicates a favorable clinical outcome in HIV-infected patients regardless of virologic response. This suggests that both immunologic and virologic markers should be used in clinical practice to evaluate treatment response.     

Cross‐Sectional Study of Respiratory Symptoms,Spirometry, and Immunologic Sensitivity in Epoxy Resin Workers

Objectives

An epoxy resin worker developed hypersensitivity pneumonitis requiring lung transplantation and had an abnormal blood lymphocyte proliferation test (LPT) to an epoxy hardener. We assessed the prevalence of symptoms, abnormal spirometry, and abnormal epoxy resin LPT results in epoxy resin workers compared to unexposed workers.

Methods

Participants completed questionnaires and underwent spirometry. We collected blood for epoxy resin LPT and calculated stimulation indices for five epoxy resin products.

Results

We compared 38 exposed to 32 unexposed workers. Higher exposed workers were more likely to report cough (OR 10.86, [1.23‐infinity], p = 0.030) or wheeze (OR 4.44, [1.00‐22.25], p = 0.049) than unexposed workers, even controlling for smoking. Higher exposed workers were more likely to have abnormal FEV1 than unexposed workers (OR 10.51, [0.86‐589.9], p = 0.071), although not statistically significant when adjusted for smoking. There were no differences in proportion of abnormal epoxy resin system LPTs between exposed and unexposed workers.

Conclusions

In summary, workers exposed to epoxy resin system chemicals were more likely to report respiratory symptoms and have abnormal FEV1 than unexposed workers. Use of epoxy resin LPT was not helpful as a biomarker of exposure and sensitization.     

A variation in the ghrelin gene increases weight and decreases insulin secretion in tall,obese children

Ghrelin is a recently recognized gut-brain peptide originally derived from the gastric mucosa. It stimulates growth hormone release, increases appetite and facilitates fat storage, and may interact with glucose metabolism. We studied the ghrelin gene in a group of 70 tall and obese children (mean age 9.4 year, Z body mass index [BMI] and Z height >3 and/or BMI percentile >99%). We found 10 single nucleotide polymorphisms. One common polymorphism of the ghrelin gene, which corresponds to an amino acid change in the tail of the prepro-ghrelin molecule, was significantly associated with children with a higher BMI (P = 0.001), and with lower insulin secretion during the first part of an oral glucose tolerance test (P = 0.05) although no difference in glucose levels was noted. This might suggest increased insulin sensitivity, although this is not supported by the lack of difference in fasting and 2 hour insulin levels; alternatively, this may be indicative of impaired first phase insulin secretion. These data suggest that variations in the ghrelin gene contribute to obesity in children and may modulate glucose-induced insulin secretion.     

Detecting subtle fingertip sensory and motor dysfunction in adults with type II diabetes

Although evidence has emerged regarding functional neural impairment of all four limbs with a diagnosis of type II diabetes (T2D), there is conflicting evidence regarding impairment in manual function with the disease. The purpose of the current study was to evaluate hand/fingertip function in T2D as compared to healthy age- and gender-matched controls. Ten adults with T2D and ten healthy age- and gender-matched control subjects underwent a battery of clinically validated and laboratory-based evaluations of sensory function, motor function, and quality of life evaluation. The T2D group exhibited sensory dysfunction and altered kinetic output and inconsistent differences in clinically-validated timed performance tasks as compared to age-matched controls. No difference in quality of life was found between the two groups. Sensory dysfunction and some timed evaluations correlated with disease severity. Linear kinetic features did not covary with diminished sensation; however, nonlinear measures did covary with sensation changes. None of the recorded measures were related to clinical diagnosis of peripheral neuropathy. The relationship among exhibited behavioral changes is discussed in terms of small fiber neuropathy, micro-vascular adaptations, and endothelial dysfunction co-occurring with T2D.     

Impact of cross-protective vaccines on epidemiological and evolutionary dynamics of influenza

Large-scale immunization has profoundly impacted control of many infectious diseases such as measles and smallpox because of the ability of vaccination campaigns to maintain long-term herd immunity and, hence, indirect protection of the unvaccinated. In the case of human influenza, such potential benefits of mass vaccination have so far proved elusive. The central difficulty is a considerable viral capacity for immune escape; new pandemic variants, as well as viral escape mutants in seasonal influenza, compromise the buildup of herd immunity from natural infection or deployment of current vaccines. Consequently, most current influenza vaccination programs focus mainly on protection of specific risk groups, rather than mass prophylactic protection. Here, we use epidemiological models to show that emerging vaccine technologies, aimed at broad-spectrum protection, could qualitatively alter this picture. We demonstrate that sustained immunization with such vaccines could--through potentially lowering transmission rates and improving herd immunity--significantly moderate both influenza pandemic and seasonal epidemics. More subtly, phylodynamic models indicate that widespread cross-protective immunization could slow the antigenic evolution of seasonal influenza; these effects have profound implications for a transition to mass vaccination strategies against human influenza, and for the management of antigenically variable viruses in general.     

CLEC-2 and Syk in the megakaryocytic/platelet lineage are essential for development

The C-type lectin receptor CLEC-2 signals through a pathway that is critically dependent on the tyrosine kinase Syk. We show that homozygous loss of either protein results in defects in brain vascular and lymphatic development, lung inflation, and perinatal lethality. Furthermore, we find that conditional deletion of Syk in the hematopoietic lineage, or conditional deletion of CLEC-2 or Syk in the megakaryocyte/platelet lineage, also causes defects in brain vascular and lymphatic development, although the mice are viable. In contrast, conditional deletion of Syk in other hematopoietic lineages had no effect on viability or brain vasculature and lymphatic development. We show that platelets, but not platelet releasate, modulate the migration and intercellular adhesion of lymphatic endothelial cells through a pathway that depends on CLEC-2 and Syk. These studies found that megakaryocyte/platelet expression of CLEC-2 and Syk is required for normal brain vasculature and lymphatic development and that platelet CLEC-2 and Syk directly modulate lymphatic endothelial cell behavior in vitro.