Translation and Validation of 'Foot Health Status Questionnaire' in Dutch.

The aim of our study was to develop a Dutch version of the Foot Health Status Questionnaire (FHSQ-NL) and evaluate its measurement properties according to the COSMIN definition (COnsensus-based Standards for the selection of health Measurement INstruments). After translation of the FSHQ, a group of 119 randomly selected patient who visited the outpatient clinic for conditions affecting the foot and ankle were asked to participate, of which103 patients were included in the analysis. The FHSQ-NL, a validated Dutch FAOS and a visual analogue scale (VAS) for pain and function were used in this study as outcomes measures. Reliability was assessed by calculating intraclass correlation coefficient (ICC), internal consistency by Cronbach's alpha, and the smallest detectable change (SDC). Construct validity was evaluated by use of a priori hypotheses concerning Spearman's correlation coefficient between FHSQ subscales and FAOS and VAS. All domains of the FHSQ-NL, besides 'General health,' indicated good internal consistency with a Cronbach's alpha ranging from 0.61 to 0.91. Test-retest reliability of all FHSQ domains was poor with an ICC ranging from 0.47 to 0.77. At individual level, the SDC ranged from 35.1 to 60.6 and at a group level (n = 50) from 5.0 to 8.6. Construct validity was supported by confirmation of 75% of all a priori hypotheses. The FHSQ-NL has good internal consistency and smallest detectable change (SDC) at group level. However, reliability and SDC on individual level show suboptimal results. Therefore, the questionnaire is more suitable for evaluating foot complaints at group level instead of individual level.

[Nasal toilet in infants with rhinitis: nasal passage crucial, so treat with xylometazoline]. / Neustoilet bij zuigelingen met rinitis.

A good nasal passage is crucial for neonates and infants, as they rely on obligate nasal breathing. Feeding problems and dyspnoea are commonly seen in infants with nasal obstruction.In this article, we emphasize the importance of relieving nasal congestion caused by an infection. An effective therapy to reduce nasal obstruction, caused by mucus, is rinsing with saline. Xylometazoline can be added if the effect of saline is insufficient. However, guidelines are often cautious with prescribing nasal decongestants in infants. These recommendations are mainly based on case reports, and often concern overdoses or other medication than xylometazoline. The risk of severe side effects with xylometazoline in young children is low if the dosage is adequate.

Influence of health insurance status on childhood cancer treatment outcomes in Kenya.

BACKGROUND: Survival of childhood cancer in high-income countries is approximately 80%, whereas in low-income countries, it is less than 10%. Limited access to health insurance in low-income settings may contribute to poor survival rates. This study evaluates the influence of health insurance status on childhood cancer treatment in a Kenyan academic hospital. METHODS: This was a retrospective study. All children diagnosed with a malignancy from 2010 until 2012 were included. Data on treatment outcomes and health insurance status at diagnosis were abstracted from patient charts. RESULTS: Of 280 patients, 34% abandoned treatment, 19% died, and 18% had progressive or relapsed disease resulting in 29% event-free survival. The majority of patients (65%) did not have health insurance at diagnosis. Treatment results differed significantly between patients with different health insurance status at diagnosis; 37% of uninsured versus 28% of insured patients abandoned treatment, and 24% of uninsured versus 37% of insured patients had event-free survival. The event-free survival estimate was significantly higher for patients with health insurance at diagnosis compared with those without (P = 0.004). Of patients without health insurance at diagnosis, 77% enrolled during treatment. Among those patients who later enrolled in health insurance, frequency of progressive or relapsed disease and deaths was significantly lower (P = 0.013, P < 0.001, respectively), while the event-free survival estimate was significantly higher (P < 0.001) compared with those who never enrolled. CONCLUSION: Childhood cancer event-free survival was 29% at a Kenyan hospital. Children without health insurance had significant lower chance of event-free survival. Childhood cancer treatment outcomes could be ameliorated by strategies that prevent treatment abandonment and improve access to health insurance.

CD40 signaling instructs chronic lymphocytic leukemia cells to attract monocytes via the CCR2 axis.

Chronic lymphocytic leukemia (CLL) cells are provided with essential survival and proliferative signals in the lymph node microenvironment. Here, CLL cells engage in various interactions with bystander cells such as T cells and macrophages. Phenotypically distinct types of tumor infiltrating macrophages can either be tumor supportive (M2) or play a role in tumor immune surveillance (M1). Although recent in vitro findings suggest a protective role for macrophages in CLL, the actual balance between these macrophage subsets in CLL lymphoid tissue is still unclear. Furthermore, the mechanism of recruitment of monocytes towards the CLL lymph node is currently unknown. Both questions are addressed in this paper. Immunofluorescence staining of lymph node samples showed macrophage skewing towards an M2 tumor-promoting phenotype. This polarization likely results from CLL-secreted soluble factors, as both patient serum and CLL-conditioned medium recapitulated the skewing effect. Considering that CLL cell cytokine secretion is affected by adjacent T cells, we next studied CLL-mediated monocyte recruitment in the presence or absence of T-cell signals. While unstimulated CLL cells were inactive, T cell-stimulated CLL cells actively recruited monocytes. This correlated with secretion of various chemokines such as C-C-motif-ligand-2,3,4,5,7,24, C-X-C-motif-ligand-5,10, and Interleukin-10. We also identified CD40L as the responsible T-cell factor that mediated recruitment, and showed that recruitment critically depended on the C-C-motif-chemokine-receptor-2 axis. These studies show that the shaping of a tumor supportive microenvironment depends on cytokinome alterations (including C-C-motif-ligand-2) that occur after interactions between CLL, T cells and monocytes. Therefore, targeted inhibition of CD40L or C-C-motif-chemokine-receptor-2 may be relevant therapeutic options.

IL-21 and CD40L signals from autologous T cells can induce antigen-independent proliferation of CLL cells.

Chronic lymphocytic leukemia (CLL) cells multiply in secondary lymphoid tissue, but the mechanisms leading to their proliferation are still uncertain. In addition to B-cell receptor (BCR)-triggered signals, other microenvironmental factors might well be involved. In proliferation centers, leukemic B cells are in close contact with CD4(+)CD40L(+) T cells. Therefore, we here dissected the signals provided by autologous activated T cells (Tact) to CLL cells. Although the gene expression profile induced by Tact was highly similar to that induced by sole CD40 signaling, an obvious difference was that Tact induced proliferation of CLL cells. We determined that stimulation with only CD40L+IL-21 was sufficient to induce robust proliferation in CLL cells. We then defined an interleukin (IL)-21-induced gene signature in CLL, containing components of Janus kinase/signal transducer and activator of transcription and apoptosis pathways, and this signature could be detected in lymph node (LN) samples from patients. Finally, we could detect IL-21 RNA and protein in LN, and IL-21 production ex vivo by LN CD4(+)CXCR5(+) follicular helper T cells. These results indicate that in addition to BCR signaling, activated T cells might contribute to CLL cell proliferation via CD40 and IL-21. Targeting these signaling pathways might offer new venues for treatment of CLL.