Childhood central nervous system tumors at MAHAK’s Pediatric Cancer Treatment and Research Center (MPCTRC), Tehran,Iran

Purpose

As central nervous system (CNS) tumors account for second most common childhood malignancies and the first cause of mortality in children with cancer, improving treatment modalities can lead to increase the health care of patients. In this study, we examined the prevalence of childhood brain tumors in patients who referred to MAHAK’s Pediatric Cancer Treatment and Research Center (MPCTRC) for treatment.

Methods

A retrospective review of all children less than 15 years old with a CNS histologically proven tumor, who presented to MPCTRC from April 2007 to April 2010, was performed. Data was analyzed by SPSS version 19 with Kolmogorov–Smirnov and Chi-square tests.

Results

There were 198 (124 boys) children eligible for the study. The majority of the tumors were infratentorial (n?=?134), and the rest were supratentorial (n?=?60) and spinal (n?=?4) cases. The median age was 6.11?±?3.65 years old. Medulloblastoma (n?=?66), low-grade glioma (n?=?52), and high-grade glioma (n?=?40) were the most common tumors. The mean duration of follow-up was 21 months. At the time of this analysis, there were 105 (53 %) children alive, 82 (41.4 %) deaths, and 11 (5.6 %) lost for follow-up. The survival rate was 51.68?±?5.22 %.

Conclusions

In contrast of high rate of death in this study, other general characteristics can serve as benchmark for improving our care for children with brain tumors in Iran.     

Predictive ability of C-reactive protein for early mortality after ischemic stroke: comparison with NIHSS score

We aimed to compare the association of high-sensitivity C-reactive protein (CRP) and National Institutes of Health Stroke Scale (NIHSS) score with mortality risk and to determine the optimal threshold of CRP for prediction of mortality in ischemic-stroke patients. A series of 162 patients with first-ever ischemic-stroke admitted within 24 h after onset of symptoms was enrolled. CRP and NIHSS score were estimated on admission and their predictive abilities for mortality at 7 days were determined by logistic-regression analyses. Receiver-Operating Characteristic (ROC) curves were depicted to identify the optimal cut-off of CRP, using the maximum Youden-index and the shortest-distance methods. Deceased patients had higher levels of CRP and NIHSS on admission (8.87 ± 7.11 vs. 2.20 ± 4.71 mg/l for CRP, and 17.31 ± 6.36 vs. 8.70 ± 4.85 U for NIHSS, respectively, P < 0.01). CRP and NIHSS were correlated with each other (r ² = 0.39, P < 0.001) and were also independently associated with increased risk of mortality [odds ratios (95 % confidence interval) of 1.16 (1.05–1.28) and 1.20 (1.07–1.35) for CRP and NIHSS, respectively, P < 0.01]. The areas under the ROC curves of CRP and NIHSS for mortality were 0.82 and 0.84, respectively. The CRP value of 2.2 mg/l was identified as the optimal cut-off value for prediction of mortality within 7 days (sensitivity: 0.81, specificity: 0.80). Thus, CRP as an independent predictor of mortality following ischemic-stroke is comparable with NIHSS and the value of 2.2 mg/l yields the optimum sensitivity and specificity for mortality prediction.     

Volume of Resected Stomach as a Predictor of Excess Weight Loss After Sleeve Gastrectomy

Background

Laparoscopic sleeve gastrectomy (LSG) is gaining popularity for the treatment of obesity. The objective of this study was to evaluate the volume of the resected stomach (VRS) as a predictor of the percentage of excess weight loss (%EWL) 1 year after LSG.

Methods

This was a single-surgeon study of prospectively collected data of patients who underwent LSG at Jordan University Hospital (February 2009 to February 2012). The VRS was measured using a standardized technique. The %EWL was calculated at 3, 6, and 12 months postoperatively. The correlation between the VRS and %EWL was statistically evaluated.

Results

Ninety patients underwent LSG during the study period. Of these, 73 patients (57 female) completed at least 1 year of follow-up and were analyzed; their body mass index was 45?±?7.6 kg/m² (33–81). The VRS was 1,337.4?±?435.2 ml (600–2,800). The %EWL was 33.6?±?11.1 % at 3 months, 48.6?±?15.5 % at 6 months, and 56.8?±?18.9 % at 12 months. A significant correlation was observed between the VRS and %EWL at 1 year (p?=?0.003). Patients with a VRS of >1,100 ml (n?=?43) achieved significantly greater %EWL at 12 months than did those with a VRS of ≤1,100 (n?=?30). Removal of >1,100 ml of gastric volume was associated with a sensitivity and specificity of 75.5 and 46.2 %, respectively, for achieving a %EWL of ≥50 %.

Conclusion

The VRS can be used as an indicator of excess weight loss 1 year after LSG.     

Advanced multiplicity adjustment methods in clinical trials

During the last decade, many novel approaches for addressing multiplicity problems arising in clinical trials have been introduced in the literature. These approaches provide great flexibility in addressing given clinical trial objectives and yet maintain strong control of the familywise error rate. In this tutorial article, we review multiple testing strategies that are related to the following: (a) recycling local significance levels to test hierarchically ordered hypotheses; (b) adapting the significance level for testing a hypothesis to the findings of testing previous hypotheses within a given test sequence, also in view of certain consistency requirements; (c) grouping hypotheses into hierarchical families of hypotheses along with recycling the significance level between those families; and (d) graphical methods that permit repeated recycling of the significance level. These four different methodologies are related to each other, and we point out some connections as we describe and illustrate them. By contrasting the main features of these approaches, our objective is to help practicing statisticians to select an appropriate method for their applications. In this regard, we discuss how to apply some of these strategies to clinical trial settings and provide algorithms to calculate critical values and adjusted p‐values for their use in practice. The methods are illustrated with several numerical examples. Copyright © 2013 John Wiley & Sons, Ltd.     

Father involvement with three-to-four-year olds at home: giving fathers a chance

This study examined fathers' perceptions regarding their home-based activities (HBA) and the influence of fathers' demographic characteristics on their perceptions and practices at home. A total of 396 fathers completed a survey questionnaire describing their demographic information, perceptions and their practices regarding their involvement in HBA. Results indicated that fathers have moderate level of practice concerning their HBA, yet they have low perception of their actual practice at HBA. In addition, there was a statistical significance in HBA due to fathers' age, educational level and specialisation which had an influence on their perceptions as well. Recommendations and implications of future research were discussed.     

Assessment of health-related quality of life among hypertensive patients: a cross-sectional study from Palestine

Aim

The ability to identify indicators of poor health-related quality of life (HRQoL) is crucial for both improving clinical care and determining targets of intervention for the prevention and treatment of disease. The main objectives of this study were to assess the HRQoL profile of the hypertensive population from Palestine, and to determine the socio-demographic and clinical characteristics associated with poor HRQoL.

Subject and methods

A cross sectional study was conducted, adopting the EuroQoL-5 Dimensions scale (EQ-5D-5 L) for the assessment of HRQoL. Hypertensive patients attending outpatients’ clinics at Al-Makhfyah primary health care clinic and from Alwatani Hospital, Nablus, Palestine were approached for study.

Results

Four hundred and ten hypertensive patients were enrolled in the study. Of these, 213 patients (52 %) were female. The average age of the study population was 58.38?±?10.65 years. HRQoL was good, with a mean EQ-5D-5 L index value and EQ visual analogue scale (EQ-VAS) score of 0.80?±?0.16 and 74.1?±?15.6 respectively. There was a significant positive correlation (r?=?0.56; p?<?0.001) between the EQ-5D-5 L index values and the reported EQ-VAS scores. A significant difference in EQ-5D-5 L index values was found among participants when grouped according to age, occupation, marital status, income, educational level, duration of disease, total number of chronic diseases, and total number of medications (Kruskal–Wallis test; p-value?<?0.05), as well as gender and therapy type (Mann–Whitney test, p-value?<?0.05).

Conclusions

This study highlighted that specific socio-demographic and disease-related characteristics of hypertensive patients as well as treatment factors were strongly associated with HRQoL. The study findings could be helpful in clinical practice, mainly in the early treatment of hypertensive patients, at a point where improving HRQoL is still possible.     

Differences in stakeholders’ and end users’ preferences of arsenic mitigation options in Bangladesh

Aim

Arsenic contamination of drinking water is a public health crisis. Since its detection in Bangladesh, the world’s most arsenic-affected country, organizations involved (i.e., stakeholders) have made great efforts by testing wells and installing safe water options. Yet, 20 million Bangladeshi are still at risk. It has been suggested that the discrepancy between stakeholders’ and end users’ preferences of arsenic mitigation options is one reason for the slow progress. Therefore, this study aimed at comparing stakeholders’ and end users’ preferences.

Subjects and methods

Three investigations were conducted in Bangladesh: a series of qualitative interviews with 22 stakeholders and two end user surveys with a total of 1,268 randomly selected households living in six arsenic-affected districts of Bangladesh.

Results

Stakeholders mostly preferred rural piped water supplies and deep tubewells, while their least preferred options were dug wells and arsenic removal filters. End users mostly preferred deep tubewells, well-sharing and rural piped water supplies, while dug wells were least preferred. End users identified several disadvantages of mitigation options, including long distances, great effort to collect water and difficult social situations. They further demonstrated moderate willingness to pay for a rural piped water supply, deep tubewells and pond sand filters, but lower willingness for other options.

Conclusion

Stakeholders’ and end users’ preferences converged for deep tubewells and rural piped water supplies, while well-sharing was preferred by end users, but not by stakeholders. The results suggest installing deep tubewells and rural piped water supplies with greater priority. Furthermore, stakeholders’ preferences to promote well-sharing should be enhanced.     

Ablation of Breast Cancer Cells Using Trastuzumab‐Functionalized Multi‐Walled Carbon Nanotubes and Trastuzumab‐Diphtheria Toxin Conjugate

Trastuzumab (Herceptin^®) is a monoclonal antibody (mAb) for specific ablation of HER2‐overexpressing malignant breast cancer cells. Intensification of antiproliferative activity of trastuzumab through construction of immunotoxins and nano‐immunoconjugates is a promising approach for treatment of cancer. In this study, trastuzumab was directly conjugated to diphtheria toxin (DT). Also, conjugates of trastuzumab and multiwalled carbon nanotubes (MWCNT) were constructed by covalent immobilization of trastuzumab onto MWCNTs. Then, antiproliferative activity of the fusion constructs against HER2‐overexpressing SK‐BR‐3 and also HER2‐negative MCF‐7 cancer cell lines were examined. Cells treated with trastuzumab‐MWCNT conjugates were irradiated with near‐infrared (NIR) light. Efficient absorption of NIR radiation and its conversion to heat by MWCNTs can be resulted to thermal ablation of cancerous cells. Our results strongly showed that both trastuzumab‐MWCNT and trastuzumab‐DT conjugates were significantly efficient in the specific killing of SK‐BR‐3 cells. Targeting of MWCNTs to cancerous cells using trastuzumab followed by exposure of cells to NIR radiation was more efficient in repression of cell proliferation than treatment for cancer cells with trastuzumab‐DT. Our results also showed that conjugation linkers can significantly affect the cytotoxicity of MWCNT‐immunoconjugates. In conclusion, our data demonstrated that trastuzumab‐MWCNT is a promising nano‐immunoconjugate for killing of HER2‐overexpressing cancerous cells.     

CD44‐Targeted Docetaxel Conjugate for Cancer Cells and Cancer Stem‐Like Cells: A Novel Hyaluronic Acid‐Based Drug Delivery System

A CD44‐targeted macromolecular conjugate of docetaxel was prepared via a pH‐sensitive linkage to hyaluronic acid and was characterized using NMR, gel permeation chromatography, and differential scanning calorimetry. The conjugated species were further evaluated in terms of drug release, cytotoxicity, cellular uptake, cell cycle inhibition, and subacute toxicity in mice. Cellular microscopic studies revealed that CD44‐expressing cells including MCF‐7 cancer stem cells and MDA‐MB‐231 metastatic breast cancer cells had internalized the conjugates via a selective receptor‐mediated mechanism, leading to cell cycle arrest in the G2/M phase. Hyaluronic acid–docetaxel conjugates showed specific toxicity only in CD44‐expressing cells in vitro, along with a decreased risk of neutropenia and dose‐dependent mortality in vivo. Hyaluronic acid–drug conjugates represent a promising and efficient platform for solubilization of sparingly soluble molecules as well as active and selective targeted delivery to cancer cells and cancer stem cells.