Epidemiology,clinical picture and long-term outcomes of FIP1L1-PDGFRA-positive myeloid neoplasm with eosinophilia: Data from 151 patients

FIP1L1-PDGFRA-positive myeloid neoplasm with eosinophilia (F/P+ MN-eo) is a rare disease: robust epidemiological data are lacking and reported issues are scarce, of low sample-size and limited follow-up. Imatinib mesylate (IM) is highly efficient but no predictive factor of relapse after discontinuation has yet been identified. One hundred and fifty-one patients with F/P+ MN-eo (143 males; mean age at diagnosis 49 years; mean annual incidence: 0.18 case per million population) were included in this retrospective nationwide study involving all French laboratories who perform the search of F/P fusion gene (study period: 2003-2019). The main organs involved included the spleen (44%), skin (32%), lungs (30%), heart (19%) and central nervous system (9%). Serum vitamin B12 and tryptase levels were elevated in 74/79 (94%) and 45/57 (79%) patients, respectively, and none of the 31 patients initially treated with corticosteroids achieved complete hematologic remission. All 148 (98%) IM-treated patients achieved complete hematologic and molecular (when tested, n = 84) responses. Forty-six patients eventually discontinued IM, among whom 20 (57%) relapsed. In multivariate analysis, time to IM initiation (continuous HR: 1,01 [0.99-1,03]; P = .05) and duration of IM treatment (continuous HR: 0,97 [0,95-0,99]; P = .004) were independent factors of relapse after discontinuation of IM. After a mean follow-up of 80 (56) months, the 1, 5- and 10-year overall survival rates in IM-treated patients were 99%, 95% and 84% respectively. In F/P+ MN-eo, prompt initiation of IM and longer treatment durations may prevent relapses after discontinuation of IM.     

‘Your whole life is lived through your teeth’: biographical disruption and experiences of tooth loss and replacement

The experience and meaning of tooth loss and replacement has varied historically and culturally but has received relatively little attention from social scientists. Our study set out to understand these experiences in the context of the arrival of newer, dental implant treatments. Semi‐structured qualitative interviews were carried out with 39 men and women who had experienced tooth loss and replacement. A thematic analysis was sensitised by previous sociological work on chronic illness, particularly Bury's notion of biographical disruption. We found that while for some individuals the loss of a tooth was relatively insignificant, for others it was devastating and disruptive. In seeking to understand this difference, the concept of biographical disruption was a helpful analytical tool. Our analysis identified two forms of disruption. The first related to the meanings of tooth loss (the neglected mouth) and denture wearing (a marker of old age). The second, embodied, disruption concerned the relationship between the self and mouth in those wearing dentures (the invaded, unreliable mouth) and could occur even where tooth loss and denture wearing had been biographically anticipated.     

Provider acceptability of Sayana® Press: results from community health workers and clinic-based providers in Uganda and Senegal

Background

Sayana® Press (SP), a subcutaneous formulation of depot medroxyprogesterone acetate (DMPA) in Uniject™, has potential to be a valuable innovation in family planning (FP) because it may overcome logistic and safety challenges in delivering intramuscular DMPA (DMPA IM). However, SP's acceptability is unknown. We measured acceptability of SP among clinic-based providers (Senegal only) and community health workers.

Study design

This open-label observational study was conducted in clinics in three districts in Senegal and community-based services in two districts in Uganda. Providers administered SP to clients seeking reinjection of DMPA IM. We conducted in-depth interviews with 86 providers (52 in Senegal, 34 in Uganda) to assess their experiences providing SP to clients.

Results

Almost all providers (84/86; 98%) preferred SP over DMPA IM. The main reason Uganda providers preferred SP was the prefilled/all-in-one design made preparation and administration easier and faster. Some providers thought the SP all-in-one feature may decrease stock outs (DMPA IM requires syringe and vial). Providers also felt clients preferred the shorter SP needle because it is less intimidating and less painful. Similarly, the main reasons Senegal providers preferred SP were its characteristics (prefilled/all-in-one) and client preference (especially less pain). They also saw a potential to increase access to FP, especially through community-based distribution. Providers from both countries reported SP introduction would be enhanced through client counseling and community engagement. Providers also said SP must be accessible, affordable and in stock.

Conclusion

Almost all providers preferred SP over DMPA IM. Provider recommendations should be considered during SP introduction planning.

Implications

We found that SP was acceptable to both clinic-based FP providers and community health workers. Providers' positive attitudes towards SP may facilitate introduction and uptake of this method.     

Repeated Nitrogen Dioxide Exposures and Eosinophilic Airway Inflammation in Asthmatics: A Randomized Crossover Study

Background: Nitrogen dioxide (NO₂), a ubiquitous atmospheric pollutant, may enhance the asthmatic response to allergens through eosinophilic activation in the airways. However, the effect of NO₂ on inflammation without allergen exposure is poorly studied.Objectives: We investigated whether repeated peaks of NO₂, at various realistic concentrations, induce changes in airway inflammation in asthmatics.Methods: Nineteen nonsmokers with asthma were exposed at rest in a double-blind, crossover study, in randomized order, to 200 ppb NO₂, 600 ppb NO₂, or clean air once for 30 min on day 1 and twice for 30 min on day 2. The three series of exposures were separated by 2 weeks. The inflammatory response in sputum was measured 6 hr (day 1), 32 hr (day 2), and 48 hr (day 3) after the first exposure, and compared with baseline values measured twice 10–30 days before the first exposure.Results: Compared with baseline measurements, the percentage of eosinophils in sputum increased by 57% after exposure to 600 ppb NO₂ (p = 0.003) but did not change significantly after exposure to 200 ppb. The slope of the association between the percentage of eosinophils and NO₂ exposure level was significant (p = 0.04). Eosinophil cationic protein in sputum was highly correlated with eosinophil count and increased significantly after exposure to 600 ppb NO₂ (p = 0.001). Lung function, which was assessed daily, was not affected by NO₂ exposure.Conclusions: We observed that repeated peak exposures of NO₂ performed without allergen exposure were associated with airway eosinophilic inflammation in asthmatics in a dose-related manner.Citation: Ezratty V, Guillossou G, Neukirch C, Dehoux M, Koscielny S, Bonay M, Cabanes PA, Samet JM, Mure P, Ropert L, Tokarek S, Lambrozo J, Aubier M. 2014. Repeated nitrogen dioxide exposures and eosinophilic airway inflammation in asthmatics: a randomized crossover study. Environ Health Perspect 122:850–855; http://dx.doi.org/10.1289/ehp.1307240