An introduction to anticancer drugs

An introduction to anticancer drugs 24.1 Introduction 24.2 The rationale behind anticancer drug therapy 24.3 Drugs used in cancer 24.3.1 Alkylating agents 24.3.2 Cytotoxic antibiotics 24.3.3 Antimetabolites 24.3.4 Microtubule inhibitors 24.3.5 Monoclonal antibodies 24.3.6 Steroid hormones and their antagonists 24.3.7 Other treatments

Validity and reliability of instruments designed to measure factors influencing the overuse of antibiotics

Background: Antibiotic overuse is a global public health issue that is influenced by several factors. The degree and prevalence of antibiotic overuse is difficult to measure directly. A more practical approach, such as the use of a psycho-social measurement instrument, might allow for the observation and assessment of patterns of antibiotic use. Study objective: The aim of this paper is to review the nature, validity, and reliability of measurement scales designed to measure factors associated with antibiotic misuse/overuse. Design: This study is descriptive and includes a systematic integration of the measurement scales used in the literature to measure factors associated with antibiotic misuse/overuse. The review included 70 international scientific publications from 1992 to 2010. Main results: Studies have presented scales to measure antibiotic misuse. However, the workup of these instruments is often not mentioned, or the scales are used with only early-phase validation, such as content or face validity. Other studies have discussed the reliability of these scales. However, the full validation process has not been discussed in any of the reviewed measurement scales. Conclusion: A reliable, fully validated measurement scale must be developed to assess the factors associated with the overuse of antibiotics. Identifying these factors will help to minimize the misuse of antibiotics.

Antibiotics overuse in children with upper respiratory tract infections in Saudi Arabia : risk factors and potential interventions

Background: Antibiotics misuse is currently one of the major public health issues worldwide. This misuse can lead to the development of bacterial resistance, increasing the burden of chronic diseases, rising costs of health services, and the development of side effects. Several factors may influence this pattern of overuse. Objectives:This article will review the pertinent factors contributing to the overuse of antibiotics worldwide, and to assess the intervention strategies to limit this overuse. Methods: studies about antibiotics use in children were reviewed from several electronic databases, such as MEDLINE and Pubmed. Results: Factors contributing to the overuse of antibiotics could include psychosocial factors, such as behaviors and attitudes (e.g. self-medication, over-the-counter medication, or patients/parents pressure), and demographic factors, such as socio-economic status and education level. Several intervention strategies were reported to be effective in reducing the overuse of antibiotics, such as health education, doctor-patient communication, and policies change. Multifaceted interventions were found to be the most effective in reducing the antibiotics overuse.

Tocotrienol as potential anticancer agent

Vitamin E is composed of two structurally similar compounds: tocopherols (TPs) and tocotrienols (T3). Despite being overshadowed by TP over the past few decades, T3 is now considered to be a promising anticancer agent due to its potent effects against a wide range of cancers. A growing body of evidence suggests that in addition to its antioxidative and pro-apoptotic functions, T3 possesses a number of anticancer properties that make it superior to TP. These include the inhibition of epithelial-to-mesenchymal transitions, the suppression of vascular endothelial growth factor tumor angiogenic pathway and the induction of antitumor immunity. More recently, T3, but not TP, has been shown to have chemosensitization and anti-cancer stem cell effects, further demonstrating the potential of T3 as an effective anticancer therapeutic agent. With most of the previous clinical studies on TP producing disappointing results, research has now focused on testing T3 as the next generation vitamin E for chemoprevention and cancer treatment. This review will summarize recent developments in the understanding of the anticancer effects of T3. We will also discuss current progress in clinical trials involving T3 as an adjuvant to conventional cancer therapy.

Assessing the overuse of antibiotics in children with URTIs in Saudi Arabia : development of the parental perception on antibiotics scale (PAPA scale)

Background: Antibiotic overuse is influenced by several factors that can only be measured using a valid and reliable psychosocial measurement instrument. This study aims to establish translation and early stage validation of an instrument recently developed by this research team to measure factors influencing the overuse of antibiotics in children with upper respiratory tract infections in Saudi Arabia. Method: The content evaluation panel was composed of area experts approached using the Delphi Technique. Experts were provided with the questionnaires iteratively, on a three-round basis until consensus on the relevance of items was reached independently. Translation was achieved by adapting Brislin’s model of translation. Results: After going through the iterative process with the experts, consensus was reached to 58 items (including demographics). Experts also pointed out some issues related to ambiguity and redundancy in some items. A final Arabic version was produced from the translation process. Conclusion: This study produced preliminary validation of the developed instrument from the experts’ contributions. Then, the instrument was translated from English to Arabic. The instrument will undergo further validation steps in the future, such as construct validity.

Assessing the overuse of antibiotics in children in Saudi Arabia : validation of the parental perception on antibiotics scale (PAPA scale)

Background Antibiotics overuse is a global public health issue influenced by several factors, of which some are parent-related psychosocial factors that can only be measured using valid and reliable psychosocial measurement instruments. The PAPA scale was developed to measure these factors and the content validity of this instrument was assessed. Aim This study further validated the recently developed instrument in terms of (1) face validity and (2) construct validity including: deciding the number and nature of factors, and item selection. Methods Questionnaires were self-administered to parents of children between the ages of 0 and 12 years old. Parents were conveniently recruited from schools’ parental meetings in the Eastern Province, Saudi Arabia. Face validity was assessed with regards to questionnaire clarity and unambiguity. Construct validity and item selection processes were conducted using Exploratory factor analysis. Results Parallel analysis and Exploratory factor analysis using principal axis factoring produced six factors in the developed instrument: knowledge and beliefs, behaviours, sources of information, adherence, awareness about antibiotics resistance, and parents’ perception regarding doctors’ prescribing behaviours. Reliability was assessed (Cronbach’s alpha = 0.78) which demonstrates the instrument as being reliable. Conclusion The ‘factors’ produced in this study coincide with the constructs contextually identified in the development phase of other instruments used to study antibiotic use. However, no other study considering perceptions of antibiotic use had gone beyond content validation of such instruments. This study is the first to constructively validate the factors underlying perceptions regarding antibiotic use in any population and in parents in particular.

Antibiotics for bronchiectasis exacerbations in children: rationale and study protocol for a randomised placebo-controlled trial

Background Despite bronchiectasis being increasingly recognised as an important cause of chronic respiratory morbidity in both indigenous and non-indigenous settings globally, high quality evidence to inform management is scarce. It is assumed that antibiotics are efficacious for all bronchiectasis exacerbations, but not all practitioners agree. Inadequately treated exacerbations may risk lung function deterioration. Our study tests the hypothesis that both oral azithromycin and amoxicillin-clavulanic acid are superior to placebo at improving resolution rates of respiratory exacerbations by day 14 in children with bronchiectasis unrelated to cystic fibrosis. Methods We are conducting a bronchiectasis exacerbation study (BEST), which is a multicentre, randomised, double-blind, double-dummy, placebo-controlled, parallel group trial, in five centres (Brisbane, Perth, Darwin, Melbourne, Auckland). In the component of BEST presented here, 189 children fulfilling inclusion criteria are randomised (allocation-concealed) to receive amoxicillin-clavulanic acid (22.5 mg/kg twice daily) with placebo-azithromycin; azithromycin (5 mg/kg daily) with placebo-amoxicillin-clavulanic acid; or placebo-azithromycin with placebo-amoxicillin-clavulanic acid for 14 days. Clinical data and a paediatric cough-specific quality of life score are obtained at baseline, at the start and resolution of exacerbations, and at day 14. In most children, blood and deep nasal swabs are also collected at the same time points. The primary outcome is the proportion of children whose exacerbations have resolved at day 14. The main secondary outcome is the paediatric cough-specific quality of life score. Other outcomes are time to next exacerbation; requirement for hospitalisation; duration of exacerbation; and spirometry data. Descriptive viral and bacteriological data from nasal samples and blood markers will also be reported. Discussion Effective, evidence-based management of exacerbations in people with bronchiectasis is clinically important. Yet, there are few randomised controlled trials (RCTs) in the neglected area of non-cystic fibrosis bronchiectasis. Indeed, no published RCTs addressing the treatment of bronchiectasis exacerbations in children exist. Our multicentre, double-blind RCT is designed to determine if azithromycin and amoxicillin-clavulanic acid, compared with placebo, improve symptom resolution on day 14 in children with acute respiratory exacerbations. Our planned assessment of the predictors of antibiotic response, the role of antibiotic-resistant respiratory pathogens, and whether early treatment with antibiotics affects duration and time to the next exacerbation, are also all novel.

Assessing the construct validity and reliability of the parental perception on antibiotics (PAPA) scales

Background: The overuse of antibiotics is becoming an increasing concern. Antibiotic resistance, which increases both the burden of disease, and the cost of health services, is perhaps the most profound impact of antibiotics overuse. Attempts have been made to develop instruments to measure the psychosocial constructs underlying antibiotics use, however, none of these instruments have undergone thorough psychometric validation. This study evaluates the psychometric properties of the Parental Perceptions on Antibiotics (PAPA) scales. The PAPA scales attempt to measure the factors influencing parental use of antibiotics in children. Methods: 1111 parents of children younger than 12 years old were recruited from primary schools’ parental meetings in the Eastern Province of Saudi Arabia from September 2012 to January 2013. The structure of the PAPA instrument was validated using Confirmatory Factor Analysis (CFA) with measurement model fit evaluated using the raw and scaled χ2, Goodness of Fit Index, and Root Mean Square Error of Approximation. Results: A five-factor model was confirmed with the model showing good fit. Constructs in the model include: Knowledge and Beliefs, Behaviors, Sources of information, Adherence, and Awareness about antibiotics resistance. The instrument was shown to have good internal consistency, and good discriminant and convergent validity. Conclusion: The availability of an instrument able to measure the psychosocial factors underlying antibiotics usage allows the risk factors underlying antibiotic use and overuse to now be investigated.