Afatinib efficacy against squamous cell carcinoma of the head and neck cell lines in vitro and in vivo.

Epidermal growth factor receptor (EGFR) inhibitors have demonstrated efficacy in squamous cell carcinoma of the head and neck (SCCHN). In addition to EGFR, other ErbB family members are expressed and activated in SCCHN. Afatinib is an ErbB family blocker that has been approved for treating patients with EGFR-mutated nonsmall cell lung cancer. We sought to determine the efficacy of afatinib in preclinical models and compare this to other EGFR-targeted agents. Afatinib efficacy was characterized in a panel of ten SCCHN cell lines and found to be most effective against cell lines amplified for EGFR. Afatinib had lower IC(50) values than did gefitinib against the same panel. Two EGFR-amplified cell lines that are resistant to gefitinib are sensitive to afatinib. Cetuximab was not found to have a synergistic effect with afatinib either in vitro or in vivo. Both afatinib and cetuximab were effective in tumor xenograft model. Afatinib is an effective agent in SCCHN especially in models with EGFR amplification

Засади та історія становлення соціального вчення Українського католицизму

In equine medicine the use of Botox® is experimental. Dosages are determined from human treatment-protocols and limited numbers of equine studies. Determination of target-muscle volume can be helpful to extrapolate human dosages. The aim of the study was to calculate a formula enabling the estimation of the deep digital flexor muscle (DDFM) volume based on distances between anatomical landmarks. Nineteen cadaveric limbs were collected and distance A (top of olecranon to Os carpi accessorium) and B (circumference of limb) were measured. Converting mathematical formulas, C was calculated: π × (((0.5B)/π)(2)) × A. DDFM volume was determined by water displacement. Linear Regression Analysis was used to analyse data. The line best fitting the observed points was: Ln(volume[ml]) = -1.89 + 0.98 × Ln(value C[cm(3)]). Correlation was highest when natural logarithm was applied to both variables and was 0.97. The calculated formula enables estimating DDFM volume of a living horse. This estimated volume can be useful to apply human Botox® treatment-protocols

Does electronic monitoring influence adherence to medication? Randomized controlled trial of measurement reactivity.

BACKGROUND: Electronic monitoring is recommended for accurate measurement of medication adherence but a possible limitation is that it may influence adherence. PURPOSE: To test the reactive effect of electronic monitoring in a randomized controlled trial. METHODS: A total of 226 adults with type 2 diabetes and HbA1c ≥58 mmol/mol were randomized to receiving their main oral glucose lowering medication in electronic containers or standard packaging. The primary outcomes were self-reported adherence measured with the MARS (Medication Adherence Report Scale; range 5-25) and HbA1c at 8 weeks. RESULTS: Non-significantly higher adherence and lower HbA1c were observed in the electronic container group (differences in means, adjusting for baseline value: MARS, 0.4 [95 % CI -0.1 to 0.8, p = 0.11]; HbA1c (mmol/mol), -1.02 [-2.73 to 0.71, p = 0.25]). CONCLUSIONS: Electronic containers may lead to a small increase in adherence but this potential limitation is outweighed by their advantages. Our findings support electronic monitoring as the method of choice in research on medication adherence. (Trial registration Current Controlled Trials ISRCT N30522359)

Designing theoretically-informed implementation interventions

Clinical and health services research is continually producing new findings that may contribute to effective and efficient patient care. However, the transfer of research findings into practice is unpredictable and can be a slow and haphazard process. Ideally, the choice of implementation strategies would be based upon evidence from randomised controlled trials or systematic reviews of a given implementation strategy. Unfortunately, reviews of implementation strategies consistently report effectiveness some, but not all of the time; possible causes of this variation are seldom reported or measured by the investigators in the original studies. Thus, any attempts to extrapolate from study settings to the real world are hampered by a lack of understanding of the effects of key elements of individuals, interventions, and the settings in which they were trialled. The explicit use of theory offers a way of addressing these issues and has a number of advantages, such as providing: a generalisable framework within which to represent the dimensions that implementation studies address, a process by which to inform the development and delivery of interventions, a guide when evaluating, and a way to allow for an exploration of potential causal mechanisms. However, the use of theory in designing implementation interventions is methodologically challenging for a number of reasons, including choosing between theories and faithfully translating theoretical constructs into interventions. The explicit use of theory offers potential advantages in terms of facilitating a better understanding of the generalisability and replicability of implementation interventions. However, this is a relatively unexplored methodological area

Intravital FRAP imaging using an E-cadherin-GFP mouse reveals disease- and drug-dependent dynamic regulation of cell-cell junctions in live tissue

E-cadherin-mediated cell-cell junctions play a prominent role in maintaining the epithelial architecture. The disruption or deregulation of these adhesions in cancer can lead to the collapse of tumor epithelia that precedes invasion and subsequent metastasis. Here we generated an E-cadherin-GFP mouse that enables intravital photobleaching and quantification of E-cadherin mobility in live tissue without affecting normal biology. We demonstrate the broad applications of this mouse by examining E-cadherin regulation in multiple tissues, including mammary, brain, liver, and kidney tissue, while specifically monitoring E-cadherin mobility during disease progression in the pancreas. We assess E-cadherin stability in native pancreatic tissue upon genetic manipulation involving Kras and p53 or in response to anti-invasive drug treatment and gain insights into the dynamic remodeling of E-cadherin during in situ cancer progression. FRAP in the E-cadherin-GFP mouse, therefore, promises to be a valuable tool to fundamentally expand our understanding of E-cadherin-mediated events in native microenvironments

A school-based intervention program in promoting leisure-time physical activity: Trial protocol

Background: Regular participation in moderate-to-vigorous physical activity (MVPA) is important to manage obesity. Physical education (PE) is considered to play an important role in promoting lifelong participation in physical activity (PA) because it provides an existing network where cost-effective interventions can be implemented to produce sustainable change in health behavior. However, the association between compulsory school PA (e.g., PE lessons) and body composition levels has received mixed support in the literature. Therefore, the present study aimed to investigate whether a school-based intervention targeting salient PA benefits and barriers grounded on the theory of planned behavior would promote young people's participation in MVPA during leisure time and reduce body mass index (BMI) of overweight students. Methods/design: A total of 171 students from 3 secondary schools in Singapore underwent the control condition followed by the intervention condition. Both the conditions consisted of PE lessons twice per week over 4 weeks. In the control condition, PE teachers encouraged students to participate in PA during leisure time without providing persuasive message. While in the intervention condition, PE teachers delivered persuasive messages that targeted the salient benefits and barriers associated with PA to the students at the last 5 to 10 min of each PE lesson. PA levels over a week were measured objectively with wrist-mounted GENEActiv Original accelerometers and subjectively with self-reporting questionnaires three times (Baseline, Post 1, and Post 2) in each condition. Student's self-reported PA level was measured using the Leisure-Time Physical Activity Participation Questionnaire and the International Physical Activity Questionnaire, and their attitudes, intentions, subjective norms and perceived behavior control towards leisure-time PA were measured with a questionnaire based on the theory of planned behavior. Furthermore, students' intention, determination and willingness to engage in leisure-time PA were compared with the other activity (e.g., doing homework, shopping). Discussion: This study will provide the evidence on the effectiveness of a cost-effective school-based intervention on reducing BMI of overweight students through promoting sustained participation in leisure-time PA. It will also address methodological issues on the gaps between objective and subjective measures of PA. Trial registration: This trial is registered with the ISRCTN registry (ISRCTN73786157, 26/10/2017, retrospectively registered)

Implementation experience during an eighteen month intervention to improve paediatric and newborn care in Kenyan district hospitals

<p>Abstract</p> <p>Background</p> <p>We have conducted an intervention study aiming to improve hospital care for children and newborns in Kenya. In judging whether an intervention achieves its aims, an understanding of how it is delivered is essential. Here, we describe how the implementation team delivered the intervention over 18 months and provide some insight into how health workers, the primary targets of the intervention, received it.</p> <p>Methods</p> <p>We used two approaches. First, a description of the intervention is based on an analysis of records of training, supervisory and feedback visits to hospitals, and brief logs of key topics discussed during telephone calls with local hospital facilitators. Record keeping was established at the start of the study for this purpose with analyses conducted at the end of the intervention period. Second, we planned a qualitative study nested within the intervention project and used in-depth interviews and small group discussions to explore health worker and facilitators' perceptions of implementation. After thematic analysis of all interview data, findings were presented, discussed, and revised with the help of hospital facilitators.</p> <p>Results</p> <p>Four hospitals received the full intervention including guidelines, training and two to three monthly support supervision and six monthly performance feedback visits. Supervisor visits, as well as providing an opportunity for interaction with administrators, health workers, and facilitators, were often used for impromptu, limited refresher training or orientation of new staff. The personal links that evolved with senior staff seemed to encourage local commitment to the aims of the intervention. Feedback seemed best provided as open meetings and discussions with administrators and staff. Supervision, although sometimes perceived as fault finding, helped local facilitators become the focal point of much activity including key roles in liaison, local monitoring and feedback, problem solving, and orientation of new staff to guidelines. In four control hospitals receiving a minimal intervention, local supervision and leadership to implement new guidelines, despite their official introduction, were largely absent.</p> <p>Conclusion</p> <p>The actual content of an intervention and how it is implemented and received may be critical determinants of whether it achieves its aims. We have carefully described our intervention approach to facilitate appraisal of the quantitative results of the intervention's effect on quality of care. Our findings suggest ongoing training, external supportive supervision, open feedback, and local facilitation may be valuable additions to more typical in-service training approaches, and may be feasible.</p

Intervention Synthesis: A Missing Link between a Systematic Review and Practical Treatment(s)

Paul Glasziou and colleagues discuss methods to guide selection of an intervention from individual trials within a systematic review. Please see later in the article for the Editors' Summary

A randomised controlled trial of a theory-based intervention to improve sun protective behaviour in adolescents ('you can still be HOT in the shade'): study protocol

Background: Most skin cancers are preventable by encouraging consistent use of sun protective behaviour. In Australia, adolescents have high levels of knowledge and awareness of the risks of skin cancer but exhibit significantly lower sun protection behaviours than adults. There is limited research aimed at understanding why people do or do not engage in sun protective behaviour, and an associated absence of theory-based interventions to improve sun safe behaviour. This paper presents the study protocol for a school-based intervention which aims to improve the sun safe behaviour of adolescents. Methods/design: Approximately 400 adolescents (aged 12-17 years) will be recruited through Queensland, Australia public and private schools and randomized to the intervention (n = 200) or 'wait-list' control group (n = 200). The intervention focuses on encouraging supportive sun protective attitudes and beliefs, fostering perceptions of normative support for sun protection behaviour, and increasing perceptions of control/self-efficacy over using sun protection. It will be delivered during three × one hour sessions over a three week period from a trained facilitator during class time. Data will be collected one week pre-intervention (Time 1), and at one week (Time 2) and four weeks (Time 3) post-intervention. Primary outcomes are intentions to sun protect and sun protection behaviour. Secondary outcomes include attitudes toward performing sun protective behaviours (i.e., attitudes), perceptions of normative support to sun protect (i.e., subjective norms, group norms, and image norms), and perceived control over performing sun protective behaviours (i.e., perceived behavioural control). Discussion: The study will provide valuable information about the effectiveness of the intervention in improving the sun protective behaviour of adolescents

Predicting intention to treat HIV-infected patients among Tanzanian and Sudanese medical and dental students using the theory of planned behaviour - a cross sectional study

<p>Abstract</p> <p>Background</p> <p>The HIV epidemic poses significant challenges to the low income countries in sub Saharan Africa (SSA), affecting the attrition rate among health care workers, their level of motivation, and absenteeism from work. Little is known about how to deal with deterioration of human resources in the health care systems. This study aimed to predict the intention to provide surgical treatment to HIV infected patients among medical- and dental students in Tanzania and Sudan using an extended version of the Theory of Planned Behaviour (TPB).</p> <p>Methods</p> <p>Four hundred and seventy five medical- and dental students at the University of Dar es Salaam (mean age, 25 yr) and 642 dental students attending 6 public and private dental faculties in Khartoum (mean age 21.7 yr) completed self-administered TPB questionnaires in 2005 and 2007, respectively.</p> <p>Results</p> <p>Both Tanzanian and Sudanese students demonstrated strong intentions to provide care for people with HIV and AIDS. Stepwise linear regression revealed that the TPB accounted for 51% (43% in Tanzania and Sudan) of the variance in intention across study sites. After having controlled for country and past behaviour, the TPB in terms of attitudes, subjective norms and perceived behavioural control accounted for 34% and moral norms for an additional 2,3% of the explainable variance in intention. Across both study sites, attitudes were the strongest predictor of intention followed in descending order by subjective norms, moral norms and perceived behavioural control.</p> <p>Conclusion</p> <p>The TPB is applicable to students' care delivery intentions in the context of HIV and AIDS across the two SSA countries investigated. It is suggested that attitudes, subjective norms, moral norms and perceived behavioural control are key factors in students' willingness to treat AIDS and HIV infected patients and should be targets of interventions aimed at improving the quality of health care delivery in this context.</p