A phagocytic route for uptake of double-stranded RNA in RNAi.

RNA interference (RNAi) has a range of physiological functions including as a defence mechanism against viruses. To protect uninfected cells in a multicellular organism, not only a cell-autonomous RNAi response is required but also a systemic one. However, the route of RNA spread in systemic RNAi remains unclear. Here we show that phagocytosis can be a route for double-stranded RNA uptake. Double-stranded RNA expressed in Escherichia coli induces robust RNAi in Drosophila S2 cells, with effectiveness comparable to that of naked dsRNA. We could separate this phagocytic uptake route from that for RNAi induced by naked dsRNA. Therefore, phagocytic uptake of dsRNA offers a potential route for systemic spread of RNAi

Developing and validating a theoretical measure of modifiable influences on hormonal therapy medication taking behaviour in women with breast cancer

Objective: Taking adjuvant hormonal therapy for 5-10 years is recommended to prevent breast cancer recurrence in those with estrogen positive disease. Despite proven clinical efficacy many women do not take their hormonal therapy as prescribed. This study reports the development and initial validation of a questionnaire measuring the behavioural determinants of hormonal therapy medication taking behaviour (MTB) based on the Theoretical Domains Framework (TDF).  Design: Women with Stage I-III breast cancer (N=223) completed the questionnaire based on the TDF. The TDF is an integrative framework consisting of 14 domains of behaviour change determinants to inform intervention design.  Main outcome measures: Items were developed from previous research, in-depth patient interviews and consultation with health professionals. Confirmatory factor analysis (CFA) was undertaken to generate the model of best fit.  Results: The final questionnaire consisted of 8 domains and CFA produced a reasonable fit (χ2(810)=942, p < 0.001; RMSEA = 0.03 ; CFI = 0.93 and WRMR=0.91) as well as internal consistency (r=0.16 to 0.64). There were adequate levels of discriminant validity for the majority of the domains.  Conclusions: A TDF based measure of the behavioural determinants of MTB was developed. Further research is needed to confirm the reliability and validity of this measure

Octopaminergic neurons have multiple targets in Drosophila larval mushroom body calyx and can modulate behavioral odor discrimination.

Discrimination of sensory signals is essential for an organism to form and retrieve memories of relevance in a given behavioral context. Sensory representations are modified dynamically by changes in behavioral state, facilitating context-dependent selection of behavior, through signals carried by noradrenergic input in mammals, or octopamine (OA) in insects. To understand the circuit mechanisms of this signaling, we characterized the function of two OA neurons, sVUM1 neurons, that originate in the subesophageal zone (SEZ) and target the input region of the memory center, the mushroom body (MB) calyx, in larval Drosophila We found that sVUM1 neurons target multiple neurons, including olfactory projection neurons (PNs), the inhibitory neuron APL, and a pair of extrinsic output neurons, but relatively few mushroom body intrinsic neurons, Kenyon cells. PN terminals carried the OA receptor Oamb, a Drosophila α1-adrenergic receptor ortholog. Using an odor discrimination learning paradigm, we showed that optogenetic activation of OA neurons compromised discrimination of similar odors but not learning ability. Our results suggest that sVUM1 neurons modify odor representations via multiple extrinsic inputs at the sensory input area to the MB olfactory learning circuit.MRC studentship, UK Genetics Society Summer scholarship, BBSRC DTP summer placement, Isaac Newton Trust

Patient Centric Pharmaceutical Drug Product Design—The Impact on Medication Adherence

Medication adherence is a growing concern for public health and poor adherence to therapy has been associated with poor health outcomes and higher costs for patients. Interventions for improving adherence need to consider the characteristics of the individual therapeutic regimens according to the needs of the patients. In particular, geriatric and paediatric populations as well as dermatological patients have special needs/preferences that should be considered when designing drug products. Patient Centric Drug Product Pharmaceutical Design (PCDPD) offers the opportunity to meet the needs and preferences of patients. Packaging, orodispersible formulations, fixed dose combinations products, multiparticulate formulations, topical formulations and 3D printing are of particular relevance in a PCDPD process. These will be addressed in this review as well as their impact on medication adherence

Persistence as a robust indicator of medication adherence-related quality and performance

Medication adherence is a priority for health systems worldwide and is widely recognised as a key component of quality of care for disease management. Adherence-related indicators were rarely explicitly included in national health policy agendas. One barrier is the lack of standardised adherence terminology and of routine measures of adherence in clinical practice. This paper discusses the possibility of developing adherence-related performance indicators highlighting the value of measuring persistence as a robust indicator of quality of care. To standardise adherence and persistence-related terminology allowing for benchmarking of adherence strategies, the European Ascertaining Barriers for Compliance (ABC) project proposed a Taxonomy of Adherence in 2012 consisting of three components: initiation, implementation, discontinuation. Persistence, which immediately precedes discontinuation, is a key element of taxonomy, which could capture adherence chronology allowing the examination of patterns of medication-taking behaviour. Advances in eHealth and Information Communication Technology (ICT) could play a major role in providing necessary structures to develop persistence indicators. We propose measuring persistence as an informative and pragmatic measure of medication-taking behaviour. Our view is to develop quality and performance indicators of persistence, which requires investing in ICT solutions enabling healthcare providers to review complete information on patients’ medication-taking patterns, as well as clinical and health outcomes

The Need to Develop Standard Measures of Patient Adherence for Big Data: Viewpoint

Despite half a century of dedicated studies, medication adherence remains far from perfect, with many patients not taking their medications as prescribed. The magnitude of this problem is rising, jeopardizing the effectiveness of evidence-based therapies. An important reason for this is the unprecedented demographic change at the beginning of the 21st century. Aging leads to multimorbidity and complex therapeutic regimens that create a fertile ground for nonadherence. As this scenario is a global problem, it needs a worldwide answer. Could this answer be provided, given the new opportunities created by the digitization of health care? Daily, health-related information is being collected in electronic health records, pharmacy dispensing databases, health insurance systems, and national health system records. These big data repositories offer a unique chance to study adherence both retrospectively and prospectively at the population level, as well as its related factors. In order to make full use of this opportunity, there is a need to develop standardized measures of adherence, which can be applied globally to big data and will inform scientific research, clinical practice, and public health. These standardized measures may also enable a better understanding of the relationship between adherence and clinical outcomes, and allow for fair benchmarking of the effectiveness and cost-effectiveness of adherence-targeting interventions. Unfortunately, despite this obvious need, such standards are still lacking. Therefore, the aim of this paper is to call for a consensus on global standards for measuring adherence with big data. More specifically, sound standards of formatting and analyzing big data are needed in order to assess, uniformly present, and compare patterns of medication adherence across studies. Wide use of these standards may improve adherence and make health care systems more effective and sustainable

Persistence as a Robust Indicator of Medication Adherence-Related Quality and Performance.

Medication adherence is a priority for health systems worldwide and is widely recognised as a key component of quality of care for disease management. Adherence-related indicators were rarely explicitly included in national health policy agendas. One barrier is the lack of standardised adherence terminology and of routine measures of adherence in clinical practice. This paper discusses the possibility of developing adherence-related performance indicators highlighting the value of measuring persistence as a robust indicator of quality of care. To standardise adherence and persistence-related terminology allowing for benchmarking of adherence strategies, the European Ascertaining Barriers for Compliance (ABC) project proposed a Taxonomy of Adherence in 2012 consisting of three components: initiation, implementation, discontinuation. Persistence, which immediately precedes discontinuation, is a key element of taxonomy, which could capture adherence chronology allowing the examination of patterns of medication-taking behaviour. Advances in eHealth and Information Communication Technology (ICT) could play a major role in providing necessary structures to develop persistence indicators. We propose measuring persistence as an informative and pragmatic measure of medication-taking behaviour. Our view is to develop quality and performance indicators of persistence, which requires investing in ICT solutions enabling healthcare providers to review complete information on patients' medication-taking patterns, as well as clinical and health outcomes

Adherence to chronic medication in older populations: application of a common protocol among three European cohorts

Purpose: The purpose of this study was to evaluate and compare medication adherence to chronic therapies in older populations across different regions in Europe. Methods: This explorative study applied a harmonized method of data extraction and analysis from pharmacy claims databases of three European countries to compare medication adherence at a cross-country level. Data were obtained for the period between January 1, 2010, and December 31, 2011. Patients (aged >= 65 years) who newly initiated to oral antidiabetics, antihyperlipidemics, or antiosteoporotics were identified and followed for over a 12-month period. Main outcome measures were medication adherence (medication possession ratio, [MPR]; implementation) and persistence on index treatment. All country-specific data sets were prepared by employing a common data input model. Outcome measures were calculated for each country and pooled using random effect models. Results: In total, 39, 186 new users were analyzed. In pooled data from the three countries, suboptimal implementation (MPR <80%) was 52.45% (95% CI: 33.43-70.79) for antihyperlipidemics, 61.35% (95% CI: 52.83-69.22) for antiosteoporotics, and 30.33% (95% CI: 25.53-35.60) for oral antidiabetics. Similarly, rates of non-persistence (discontinuation) were 55.63% (95% CI: 35.24-74.29) for antihyperlipidemics, 60.24% (95% CI: 45.35-73.46) for antiosteoporotics, and 46.80% (95% CI: 36.40-57.4) for oral antidiabetics. Conclusion: Medication adherence was suboptimal with >50% of older people non-adherent to antihyperlipidemics and antiosteoporotics in the three European cohorts. However, the degree of variability in adherence rates among the three countries was high. A harmonized method of data extraction and analysis across health-related database in Europe is useful to compare medication-taking behavior at a cross-country level