BACKGROUNDDespite the revolutionary success of introducing tyrosine kinase inhibitors (TKIs), such as imatinib mesylate (IM), for treating chronic myeloid leukemia (CML), a substantial proportion of patients’ treatments fail.AIMThis study investigates the correlation between patient adherence and failure of TKIs’ treatment in a follow-up study.METHODSThis is a follow-up study of a new cohort of CML patients. Adherence to IM is assessed using the Medication Event Monitoring System (MEMS 6 TrackCap, AARDEX Ltd). The 9-item Morisky Medication Adherence Scale, medication possession ratio (MPR) calculation, and the electronic medical records are used for identifying potential factors that influence adherence. Clinical outcomes are assessed according to the European Leukemia Net 2013 guidelines via reverse transcriptase quantitative polymerase chain reaction measurement of the level of BCR-ABL1 transcripts in peripheral blood. Response is classified at the hematological, cytogenetic, and molecular levels into optimal, suboptimal, or failure.RESULTSA total of 36 CML patients (5 citizens and 31 noncitizen residents) consented to participate in the study. The overall mean MEMS score was 89. Of the 36 patients, 22 (61%) were classified as adherent (mean: 95) and 14 (39%) were classified as nonadherent (mean: 80.2). Adherent patients were significantly more likely to obtain optimal response (95%) compared to the nonadherent group (14.3%; P < 0.0001). The rate of poor adherence was as high as 39% using MEMS, which correlates with 37% treatment failure rate. The survey results show that 97% of patients increased the IM dose by themselves when they felt unwell and 31% of them took the missing IM dose when they remembered. Other factors known to influence adherence show that half of patients developed one or more side effects, 65% of patients experienced lack of funds, 13% of patients declared unavailability of the drug in the NCCCR pharmacy, and 72% of patients believed that IM would cure the disease. The MPR results reveal that 16% of patients had poor access to treatment through the hospital pharmacy.DISCUSSION AND CONCLUSIONThis is the first prospective study to evaluate CML patients’ adherence and response to IM in Qatar. The high rate of treatment failure observed in Qatar is explained by poor adherence. An economic factor (unaffordable drug prices) is one of the main causes of nonadherence and efforts should be made locally to improve access to medication for cancer diseases. Other risk factors associated with poor adherence could be improved by close monitoring and dose adjustment. Monitoring risk factors for poor adherence and patient education that include direct communication between the health-care teams, doctors, nurses, pharmacists, and patients are essential components for maximizing the benefits of TKI therapy and could rectify this problem. The preliminary results show that patients’ response to treatment may be directly linked to patients’ adherence to treatment. However, further in-depth and specific analysis...
Bullying and cyberbullying have severe psychological and legal consequences for those involved. However, it is unclear how or even if previous experience of bullying and cyberbullying is considered in mental health assessments. Furthermore, the relevance and effectiveness of current legal solutions has been debated extensively, resulting in a desire for a specific legislation. The purpose of this study is to investigate the psychological and legal components of bullying and cyberbullying. This is a qualitative research that includes interviews with five practitioner psychologists and four lawyers in the United Kingdom (UK). Thematic analysis revealed three main themes. One theme is related to the definition, characteristics, and impact of bullying and cyberbullying and the need for more discussion among the psychological and legal professions. Another theme is related to current professional procedures and the inclusion of questions about bullying and cyberbullying in psychological risk assessments. The third theme emphasised the importance of intervention through education. Two key messages were highlighted by the lawyers: ample yet problematic legislation exists, and knowledge will ensure legal success. The study recommends the necessity of performing revisions in the clinical psychological practices and assessments, and the legal policies regarding bullying and cyberbullying. In addition to improving legal success, this will reduce bullying prevalence rates, psychological distress, and psychopathology that can be comorbid or emerge as a result of this behaviour.
Cyberbullying is a worldwide problem affecting mental health, education, safety and general well-being for individuals across the globe. Despite the widespread availability of the Internet, research into prevalence rates of cyberbullying in Qatar is lacking and legislating for the crime has been slow to develop. Recently there have been some positive initiatives in the country such as a Cybercrime Prevention Law, the development of a National ICT Strategy, and a website detailing safe practice guidelines for Internet usage. However, the implementation and usage of these initiatives are still limited and there is a lack of awareness of cyberbullying in Qatar. As a result, the risk factors and consequences among school-aged children are unknown. The current paper presents an evaluation of the legislative and public policy solutions to cyberbullying available in Qatar, and outlines the critical challenges that could potentially face educators in shaping best practice guidelines for the future.
Background: Imatinib is failing as a first line treatment in more than 40% of chronic myeloid leukemia (CML) patients in Qatar. We thus investigated ABL1 kinase domain mutations and additional chromosomal abnormalities (ACAs) as underlying mechanisms to explain this high rate of treatment failure. Methods: Between November 2006 and December 2011, all CML patients in Qatar were studied for BCR-ABL1 kinase domain mutations and ACAs. Total RNA was extracted and cDNA was produced via reverse transcriptase polymerase chain reaction (RT-PCR). PCR was used with special precautions to avoid amplification of wild type ABL1; the ABL1 kinase domain was then screened for mutations by direct DNA sequencing technology to detect the emergence of mutant clone. Cytogenetic analysis of bone marrow (BM) metaphases and fluorescence in situ hybridization (FISH) of peripheral blood (PB) and BM interphases were performed according to standard protocols. European Leukemia Net (ELN) response criteria were employed to identify the failing cases. Results: 26 out of 33 CML patients were eligible for the study, 22 CP and 4 AP. 14 failed Imatinib treatment, 2 had BCR-ABL1 kinase domain mutations; one patient had the G1739A mutation which leads to the exchange of glutamic acid at position 459 to lysine (E459K) (rs1064156) in the c-terminal loop while the other patient had a unique insertion of three nucleotides (AAG) at position 1432 which adds an amino acid Lysine to position 356 of the catalytic domain and a complex karyotyping at diagnosis, 6 had additional chromosomal abnormalities as an underlying mechanism of resistance, 4 patients had no identifiable cause of resistance and 2 patients were intolerant to treatment. There was a significant difference in median overall survival between patients with Ph chromosome only and patients with ACAs. Conclusions: In this study as we continued observing CML patients for nearly 5 years, the Imatinib failure reached as high as 54%. The resistance rate observed in Qatar is still higher than that reported by the IRIS study which is as high as 35%. In our cohort of CML patients, point mutation and unique tri-nucleotide insertions were identified. However, these mutations could explain only 14% of treatment failure. Additional chromosomal abnormalities were the most common cause of Imatinib failure in our patients' cohort and were documented in 50% of cases. 14% of patients stopped IM due to intolerance; and the mechanisms of resistance remained unknown in 28% of patients. Other causes such as patients' adherence to Imatitinb is being prospectively investigated.
Most cases of chronic myeloid leukemia (CML) are associated with the presence of BCR-ABL1 fusion gene; a molecular anomaly that introduced targeting therapy to CML. This study was setup primarily to optimize the real-time quantification detection of BCR-ABL1 transcripts, in order to pave the way for using this method as a diagnostic tool to support the clinical management of CML patients in Qatar. A secondary objective was to evaluate the response of CML patients to Imatinib (IM) and exploit adaption of this technique as an indicator of emerging drug resistance reported in Qatar. Peripheral blood (PB) samples from 26 CML patients receiving Imatinib, were analysed via serial Real-time quantitative polymerase chain reaction (RT-qPCR) to monitor the ratio of BCR-ABL1 to normal ABL1 transcripts. EuropeanLeukemia Net (ELN) 2006 and 2009 guidelines were employed to assess the molecular response to Imatinib. For patients to be classified as optimal responders, major molecular response (MMR) had to be achieved by 18 months of treatment. Patients responding to Imatinib achieved major molecular response (MMR) during the 1st year of treatment; while patients who resisted Imatinib treatment did not achieve any molecular response within this time frame. This was the first molecular study to evaluate the molecular response of CML patients (citizens and residents) to IM in Qatar.
Protein tyrosine phosphatase receptor gamma (PTPRG) is a member of the receptor-like family protein tyrosine phosphatases and acts as a tumor suppressor gene in different neoplasms. Recent studies reported the down-regulation of PTPRG expression levels in Chronic Myeloid Leukemia disease (CML). In addition, the BCR-ABL1 transcript level is currently a key predictive biomarker of CML response to treatment with Tyrosine Kinase Inhibitors (TKIs). The aim of this study was to employ flow cytometry to monitor the changes in the expression level of PTPRG in the white blood cells (WBCs) of CML patients at the time of diagnosis and following treatment with TKIs. WBCs from peripheral blood of 21 CML patients were extracted at diagnosis and during follow up along with seven healthy individuals. The PTPRG expression level was determined at protein and mRNA levels by both flow cytometry with monoclonal antibody (TPγ B9-2) and RT-qPCR, and BCR-ABL1 transcript by RT-qPCR, respectively. PTPRG expression was found to be lower in the neutrophils and monocytes of CML patients at time of diagnosis compared to healthy individuals. Treatment with TKIs nilotinib and Imatinib Mesylate restored the expression of PTPRG in the WBCs of CML patients to levels observed in healthy controls. Moreover, restoration levels were greatest in optimal responders and occurred earlier with nilotinib compared to imatinib. Our results support the measurement of PTPRG expression level in the WBCs of CML patients by flow cytometry as a monitoring tool for the response to treatment with TKIs in CML patients.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Over the last decade, research into the negative effects of problematic internet use has greatly increased. The current study adopted a mediation-moderation model in exploring the relationship between problematic internet use and substance abuse (drinking, drug use, and smoking tobacco cigarettes) among 1,613 adolescents (aged 10–16) in the UK. The findings of the study revealed a significant positive correlation between problematic internet use and substance abuse, which is mediated by traditional and cyber bullying and victimisation. Furthermore, the parent–child relationship was found to be a protective factor that moderated the correlation between problematic internet use and substance abuse and the correlation between problematic internet use and traditional bullying. The study emphasises the critical need to reduce problematic internet use among adolescents as a risk factor for involvement in bullying as perpetrators and victims, in addition to substance abuse. Furthermore, the findings of the study highlight the importance of a good parent–child relationship as a protective factor among adolescents. In light of the findings of the study, interventions for reducing problematic internet use taking into account bullying and the parent–child relationship are needed among adolescents.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.