Surprisingly, blood pressure was mentioned neither in Fleming and colleagues' discussion of reference ranges nor in the accompanying Comment by Rosalind Smyth.2 In a cross-sectional study of more ...than 1000 healthy Chinese children aged 1-12 years in a community setting, we derived centile curves for blood pressure, heart rate, and respiratory rate and compared these with the Advanced Paediatric Life Support (APLS) reference ranges.3 We found that, for children aged 2-12 years, the mean value for blood pressure was significantly higher than APLS mean values, whereas the mean values for heart rate and respiratory rate were significantly lower. ... they are based on US populations, and studies of normal ranges of blood pressure in both Italy and Norway suggest that the values for European children might be up to 10 mm Hg higher than those presented in the US tables.3,4 We agree with Chan and colleagues that it is valuable to derive blood pressure reference tables for different regions of the world, taking into account key factors such as age, body size, and method of measurement.
... the ACCOMPLISH trial4 found that, in high-risk patients with hypertension, benazepril plus amlodipine was superior to benazepril plus hydro chlorothiazide in reducing blood pressure and ...cardiovascular events. Since benazepril plus amlodipine is an option to improve cardiovascular outcomes in patients with an indication for initial combination treatment, Brown and colleagues, and the sponsor of the ACCELERATE trial, should tell us why the control group of their study was not given benazepril plus amlodipine rather than aliskiren or amlodipine monotherapy. ... no evidence is available that aliskiren plus amlodipine can reduce blood pressure and cardiovascular events at least as effectively as benazepril plus amlodipine. ... Brown and colleagues' conclusion that the combination of aliskiren plus amlodipine can be recommended for routine initial blood pressure reduction1 is not sound.
Purpose
Quantitative MRI (qMRI) was performed using a 1.5T protocol that includes a novel chemical exchange saturation transfer/magnetization transfer (CEST/MT) approach. The purpose of this ...prospective study was to determine if qMRI metrics at baseline, at the 10th and 20th fraction during a 30 fraction/6 week standard chemoradiation (CRT) schedule, and at 1 month following treatment could be an early indicator of response for glioblastoma (GBM).
Methods
The study included 51 newly diagnosed GBM patients. Four regions-of-interest (ROI) were analyzed: (i) the radiation defined clinical target volume (CTV), (ii) radiation defined gross tumor volume (GTV), (iii) enhancing-tumor regions, and (iv) FLAIR-hyperintense regions. Quantitative CEST, MT, T
1
and T
2
parameters were compared between those patients progressing within 6.9 months (early), and those progressing after CRT (late), using mixed modelling. Exploratory predictive modelling was performed to identify significant predictors of early progression using a multivariable LASSO model.
Results
Results were dependent on the specific tumor ROI analyzed and the imaging time point. The baseline CEST asymmetry within the CTV was significantly higher in the early progression cohort. Other significant predictors included the T
2
of the MT pools (for semi-solid at fraction 20 and water at 1 month after CRT), the exchange rate (at fraction 20) and the MGMT methylation status.
Conclusions
We observe the potential for multiparametric qMRI, including a novel pulsed CEST/MT approach, to show potential in distinguishing early from late progression GBM cohorts. Ultimately, the goal is to personalize therapeutic decisions and treatment adaptation based on non-invasive imaging-based biomarkers.
•Treatment outcomes of 3328 NPC patient treated with IMRT in Hong Kong.•8 year local/regional control remained promising.•Confirmed benefits of concurrent chemotherapy with IMRT.•Additional ...chemotherapy onto backbone of concurrent chemo-irradiation warrants further investigation.•Various severe symptomatic complications after IMRT remained low.
To evaluate treatment outcomes, failure patterns and late toxicities in patients with nasopharyngeal carcinoma (NPC) treated by intensity modulated radiotherapy (IMRT) in 6 public hospitals in Hong Kong over a 10-year period from 2001 to 2010.
Eligible patients were identified through the Hong Kong Cancer Registry data base. Clinical information was retrieved and verified by oncologists working in the individual centers. Treatment details, survival outcomes and late toxicities were analyzed.
A total of 3328 patients were recruited. The median follow-up time was 80.2 months. The 8-year actuarial overall survival (OS), local failure-free survival (LFFS), regional failure-free survival (RFFS), distant failure free survival (DFFS), progression-free survival (PFS) for the whole group was 68.5%, 85.8%, 91.5%, 81.5% and 62.6% respectively. Male gender, older age, advanced T and N stage were adverse prognostic factors for OS, DFFS and PFS, whereas use of chemotherapy in form of concurrent chemo-irradiation (CRT), neoadjuvant + CRT, or CRT + adjuvant chemotherapy were favorable prognostic factors for OS and PFS. The local control was adversely affected by advanced T stage. N stage remained as the single adverse prognostic factor for regional control. Distant metastasis was the commonest site of failure.
IMRT is an effective treatment for NPC with excellent overall loco-regional control. Distant metastasis is the major site of failure. Concurrent chemotherapy with cisplatin has an established role in NPC patients treated by IMRT.
Suboptimum adherence to preventive asthma treatment is associated with substantial morbidity and mortality, yet adherence often remains poor. We aimed to investigate whether use of an inhaler with ...audiovisual reminders leads to improved adherence and asthma outcomes in school-aged children who presented to the emergency department with an asthma exacerbation.
We did a randomised controlled trial in patients aged 6-15 years who attended the regional emergency department in Auckland, New Zealand with an asthma exacerbation and were on regular inhaled corticosteroids. Using a simple, unrestricted block randomisation with block sizes of 200, we randomly assigned patients to receive an electronic monitoring device for use with their preventer inhaler with the audiovisual reminder functions either enabled to support adherence to inhaled corticosteroids (intervention group) or disabled (control group). Participants were followed up every 2 months for 6 months. The primary outcomes were adherence to preventive inhaled corticosteroids and number of days absent from school for any reason. Asthma control was assessed as a secondary outcome. All analyses were done in the intention-to-treat population. This trial is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12613001353785.
The study took place between May 10, 2010, and Feb 26, 2012. We randomly assigned 220 patients, 110 to the intervention group and 110 to the control group. Median percentage adherence was 84% (10th percentile 54%, 90th percentile 96%) in the intervention group, compared with 30% (8%, 68%) in the control group (p<0·0001). The proportion of days absent from school for any reason was 1·9% (10th percentile 0·0%, 90th percentile 7·9%) in the intervention group and 1·7% (0·0%, 8·6%) in the control group. The change in asthma morbidity score from baseline to 6 months was significantly greater in the intervention group than in the control group (p=0·008), with a reduction of 2·0 points from a mean baseline score of 9·3 (SD 2·2) to 7·3 (2·1) in the intervention group, compared with a reduction of 1·2 points from a baseline of 9·2 (2·5) to 8·0 (2·2) in the control group.
Use of an electronic monitoring device with an audiovisual reminder led to significant improvements in adherence to inhaled corticosteroids in school-aged children with asthma. This intervention could be beneficial for the improvement of asthma control in patients for whom poor asthma control is related to poor adherence.
Health Research Council of New Zealand and Cure Kids.
Abstract Background The current standard treatment for locoregionally advanced nasopharyngeal carcinoma (NPC) was conventional–fractionation radiotherapy plus concurrent–adjuvant chemotherapy as ...recommended by the Intergroup-0099 Study. This combined analysis of the NPC-9901 and the NPC-9902 Trials aims to provide more comprehensive data to evaluate the efficacy of the Intergroup-0099 regimen and the contributing factors. Methods Eligible patients with stage III-IVB non-keratinizing NPC were randomly assigned to radiotherapy-alone (RTi group: 218 patients) or chemoradiotherapy (CRTi group: 223 patients) using cisplatin (100 mg/m2 ) for three cycles in concurrence with radiotherapy, followed by cisplatin (80 mg/m2 ) plus fluorouracil (1000 mg/m2 /day for 4 days) for three cycles. The median follow-up was 6.1 years. Findings Comparison by intention-to-treat showed that the CRTi group achieved significant improvement in overall failure-free rate (FFR), locoregional-FFR and cancer-specific survival ( p ⩽ 0.019); but the improvements for distant-FFR and overall survival (OS) were statistically insignificant ( p ⩾ 0.14). Further exploratory studies based on actual treatment showed that an additional improvement achieved was a significant gain in OS (CRTa versus RTa group: 72% versus 63% at 5-year, p = 0.037). Multivariate analyses showed that the dose of cisplatin during the concurrent phase had significant impact on locoregional-FFR and OS, while that of fluorouracil during the adjuvant phase was significant for distant-FFR. The 5-year locoregional-FFR for patients who received 0–1, 2 and 3 concurrent cycles were 79%, 88% and 88%, respectively; the corresponding distant-FFR by adjuvant cycles were 68%, 78% and 77%, respectively. Interpretation Our results support the current practice of adding concurrent cisplatin plus adjuvant cisplatin-fluorouracil to radiotherapy for treating patients with locoregionally advanced NPC. The concurrent phase is important for locoregional control and survival, cisplatin 200 mg/m2 in two concurrent cycles might be adequate. Additional chemotherapy using fluorouracil-containing combination contributed to improving distant control.
Many sarcomas with DICER1 pathogenic variants (PVs) exhibit a characteristic morphology, including a subepithelial layer of malignant mesenchymal cells, areas of rhabdomyoblastic differentiation and ...cartilaginous and/or osseous elements. We report 5 DICER1-associated neoplasms (1 moderately to poorly differentiated Sertoli Leydig cell tumour and 4 sarcomas) containing variable amounts of neuroectodermal elements. The neoplasms predominantly involved or were in close proximity to the female genital tract (ovary, uterine corpus, abdominal and pelvic cavity) and occurred in females aged 14 months to 54 years. The neuroectodermal elements were characterised by solid and tubular/rosette-like patterns and variable immunoreactivity with SALL4 and neuroendocrine markers. In some cases, the neuroectodermal component was focal while in others it was exclusive. In one case, the focal neuroectodermal component within an ovarian Sertoli Leydig cell tumour resulted in extraovarian metastasis. In reporting these cases, we suggest that neuroectodermal elements, including pure neuroectodermal tumours, are part of the morphological spectrum of DICER1-associated neoplasms. It is important that pathologists recognize that a neuroectodermal component (often admixed with other elements) may be a feature of such neoplasms. This will facilitate appropriate tumour and/or germline testing which could lead to the identification of germline DICER1 PVs (DICER1 syndrome). Three of the patients we report were subsequently shown to have a germline DICER1 PV.
•We report 5 DICER1-associated neoplasms containing variable amounts of neuroectodermal elements.•The neuroectodermal elements exhibited variable immunoreactivity with SALL4 and neuroendocrine markers.•We suggest that neuroectodermal elements are part of the morphological spectrum of DICER1-associated neoplasms.
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