Chapter 4: Effective Search Strategies for Systematic Reviews of Medical Tests

This article discusses techniques that are appropriate when developing search strategies for systematic reviews of medical tests. This includes general advice for searching for systematic reviews and issues specific to systematic reviews of medical tests. Diagnostic search filters are currently not sufficiently developed for use when searching for systematic reviews. Instead, authors should construct a highly sensitive search strategy that uses both controlled vocabulary and text words. A comprehensive search should include multiple databases and sources of grey literature. A list of subject-specific databases is included in this article

Compliance and persistence with osteoporosis medications: A critical review of the literature

It is widely acknowledged that compliance and persistence with oral osteoporosis medications, particularly with bisphosphonates, is poor. Several excellent reviews have been written on compliance and persistence with osteoporosis medications and have discussed improvements seen with extended dosing intervals. This review begins with studies on extended dosing intervals to examine the limitations of administrative claims data. It also looks at compliance and persistence across multiple medical conditions, examining the importance of prescription fulfillment, intentional choice, causation and possible interventions

Eliciting Dirichlet and Gaussian copula prior distributions for multinomial models

In this paper, we propose novel methods of quantifying expert opinion about prior distributions for multinomial models. Two different multivariate priors are elicited using median and quartile assessments of the multinomial probabilities. First, we start by eliciting a univariate beta distribution for the probability of each category. Then we elicit the hyperparameters of the Dirichlet distribution, as a tractable conjugate prior, from those of the univariate betas through various forms of reconciliation using least-squares techniques. However, a multivariate copula function will give a more flexible correlation structure between multinomial parameters if it is used as their multivariate prior distribution. So, second, we use beta marginal distributions to construct a Gaussian copula as a multivariate normal distribution function that binds these marginals and expresses the dependence structure between them. The proposed method elicits a positive-definite correlation matrix of this Gaussian copula. The two proposed methods are designed to be used through interactive graphical software written in Java

Adherence to treatment in children and adolescents with cystic fibrosis:a cross-sectional, multi-method study investigating the influence of beliefs about treatment and parental depressive symptoms

Background: Adherence to treatment is often reported to be low in children with cystic fibrosis. Adherence in cystic fibrosis is an important research area and more research is needed to better understand family barriers to adherence in order for clinicians to provide appropriate intervention. The aim of this study was to evaluate adherence to enzyme supplements, vitamins and chest physiotherapy in children with cystic fibrosis and to determine if any modifiable risk factors are associated with adherence. Methods: A sample of 100 children (≤18 years) with cystic fibrosis (44 male; median [range] 10.1 [0.2-18.6] years) and their parents were recruited to the study from the Northern Ireland Paediatric Cystic Fibrosis Centre. Adherence to enzyme supplements, vitamins and chest physiotherapy was assessed using a multi-method approach including; Medication Adherence Report Scale, pharmacy prescription refill data and general practitioner prescription issue data. Beliefs about treatments were assessed using refined versions of the Beliefs about Medicines Questionnaire-specific. Parental depressive symptoms were assessed using the Center for Epidemiologic Studies Depression Scale. Results: Using the multi-method approach 72% of children were classified as low-adherers to enzyme supplements, 59% low-adherers to vitamins and 49% low-adherers to chest physiotherapy. Variations in adherence were observed between measurement methods, treatments and respondents. Parental necessity beliefs and child age were significant independent predictors of child adherence to enzyme supplements and chest physiotherapy, but parental depressive symptoms were not found to be predictive of adherence. Conclusions: Child age and parental beliefs about treatments should be taken into account by clinicians when addressing adherence at routine clinic appointments. Low adherence is more likely to occur in older children, whereas, better adherence to cystic fibrosis therapies is more likely in children whose parents strongly believe the treatments are necessary. The necessity of treatments should be reinforced regularly to both parents and children

Impaired immune responses in the lungs of aged mice following influenza infection

<p>Abstract</p> <p>Background</p> <p>Each year, influenza virus infection causes severe morbidity and mortality, particularly in the most susceptible groups including children, the elderly (>65 years-old) and people with chronic respiratory diseases. Among the several factors that contribute to the increased susceptibility in elderly populations are the higher prevalence of chronic diseases (<it>e.g</it>. diabetes) and the senescence of the immune system.</p> <p>Methods</p> <p>In this study, aged and adult mice were infected with sublethal doses of influenza virus (A/Puerto Rico/8/1934). Differences in weight loss, morbidity, virus titer and the kinetics of lung infiltration with cells of the innate and adaptive immune responses were analyzed. Additionally, the main cytokines and chemokines produced by these cells were also assayed.</p> <p>Results</p> <p>Compared to adult mice, aged mice had higher morbidity, lost weight more rapidly, and recovered more slowly from infection. There was a delay in the accumulation of granulocytic cells and conventional dendritic cells (cDCs), but not macrophages in the lungs of aged mice compared to adult animals. The delayed infiltration kinetics of APCs in aged animals correlated with alteration in their activation (CD40 expression), which also correlated with a delayed detection of cytokines and chemokines in lung homogenates. This was associated with retarded lung infiltration by natural killer (NK), CD4⁺and CD8⁺T-cells. Furthermore, the percentage of activated (CD69+) influenza-specific and IL-2 producer CD8+ T-cells was higher in adult mice compared to aged ones. Additionally, activation (CD69+) of adult B-cells was earlier and correlated with a quicker development of neutralizing antibodies in adult animals.</p> <p>Conclusion</p> <p>Overall, alterations in APC priming and activation lead to delayed production of cytokines and chemokines in the lungs that ultimately affected the infiltration of immune cells following influenza infection. This resulted in delayed activation of the adaptive immune response and subsequent delay in clearance of virus and prolonged illness in aged animals. Since the elderly are the fastest growing segment of the population in developed countries, a better understanding of the changes that occur in the immune system during the aging process is a priority for the development of new vaccines and adjuvants to improve the immune responses in this population.</p

Development and evaluation of a quality score for abstracts

BACKGROUND: The evaluation of abstracts for scientific meetings has been shown to suffer from poor inter observer reliability. A measure was developed to assess the formal quality of abstract submissions in a standardized way. METHODS: Item selection was based on scoring systems for full reports, taking into account published guidelines for structured abstracts. Interrater agreement was examined using a random sample of submissions to the American Gastroenterological Association, stratified for research type (n = 100, 1992–1995). For construct validity, the association of formal quality with acceptance for presentation was examined. A questionnaire to expert reviewers evaluated sensibility items, such as ease of use and comprehensiveness. RESULTS: The index comprised 19 items. The summary quality scores showed good interrater agreement (intra class coefficient 0.60 – 0.81). Good abstract quality was associated with abstract acceptance for presentation at the meeting. The instrument was found to be acceptable by expert reviewers. CONCLUSION: A quality index was developed for the evaluation of scientific meeting abstracts which was shown to be reliable, valid and useful

Characteristics of control group participants who increased their physical activity in a cluster-randomized lifestyle intervention trial

<p>Abstract</p> <p>Background</p> <p>Meaningful improvement in physical activity among control group participants in lifestyle intervention trials is not an uncommon finding, and may be partly explained by participant characteristics. This study investigated which baseline demographic, health and behavioural characteristics were predictive of successful improvement in physical activity in usual care group participants recruited into a telephone-delivered physical activity and diet intervention trial, and descriptively compared these characteristics with those that were predictive of improvement among intervention group participants.</p> <p>Methods</p> <p>Data come from the Logan Healthy Living Program, a primary care-based, cluster-randomized controlled trial of a physical activity and diet intervention. Multivariable logistic regression models examined variables predictive of an improvement of at least 60 minutes per week of moderate-to-vigorous intensity physical activity among usual care (n = 166) and intervention group (n = 175) participants.</p> <p>Results</p> <p>Baseline variables predictive of a meaningful change in physical activity were different for the usual care and intervention groups. Being retired and completing secondary school (but no further education) were predictive of physical activity improvement for usual care group participants, whereas only baseline level of physical activity was predictive of improvement for intervention group participants. Higher body mass index and being unmarried may also be predictors of physical activity improvement for usual care participants.</p> <p>Conclusion</p> <p>This is the first study to examine differences in predictors of physical activity improvement between intervention group and control group participants enrolled in a physical activity intervention trial. While further empirical research is necessary to confirm findings, results suggest that participants with certain socio-demographic characteristics may respond favourably to minimal intensity interventions akin to the treatment delivered to participants in a usual care group. In future physical activity intervention trials, it may be possible to screen participants for baseline characteristics in order to target minimal-intensity interventions to those most likely to benefit. (Australian Clinical Trials Registry, <url>http://www.anzctr.org.au/default.aspx</url>, ACTRN012607000195459)</p

Discovery of Dual-Action Membrane-Anchored Modulators of Incretin Receptors

The glucose-dependent insulinotropic polypeptide (GIP) and the glucagon-like peptide-1 (GLP-1) receptors are considered complementary therapeutic targets for type 2 diabetes. Using recombinant membrane-tethered ligand (MTL) technology, the present study focused on defining optimized modulators of these receptors, as well as exploring how local anchoring influences soluble peptide function.Serial substitution of residue 7 in membrane-tethered GIP (tGIP) led to a wide range of activities at the GIP receptor, with [G(7)]tGIP showing enhanced efficacy compared to the wild type construct. In contrast, introduction of G(7) into the related ligands, tGLP-1 and tethered exendin-4 (tEXE4), did not affect signaling at the cognate GLP-1 receptor. Both soluble and tethered GIP and GLP-1 were selective activators of their respective receptors. Although soluble EXE4 is highly selective for the GLP-1 receptor, unexpectedly, tethered EXE4 was found to be a potent activator of both the GLP-1 and GIP receptors. Diverging from the pharmacological properties of soluble and tethered GIP, the newly identified GIP-R agonists, (i.e. [G(7)]tGIP and tEXE4) failed to trigger cognate receptor endocytosis. In an attempt to recapitulate the dual agonism observed with tEXE4, we conjugated soluble EXE4 to a lipid moiety. Not only did this soluble peptide activate both the GLP-1 and GIP receptors but, when added to receptor expressing cells, the activity persists despite serial washes.These findings suggest that conversion of a recombinant MTL to a soluble membrane anchored equivalent offers a means to prolong ligand function, as well as to design agonists that can simultaneously act on more than one therapeutic target