Saliva proteome research: current status and future outlook

Human saliva harbours proteins of clinical relevance and about 30% of blood proteins are also present in saliva. This highlights that saliva can be used for clinical applications just as urine or blood. However, the translation of salivary biomarker discoveries into clinical settings is hampered by the dynamics and complexity of the salivary proteome. This review focuses on the current status of technological developments and achievements relating to approaches for unravelling the human salivary proteome. We discuss the dynamics of the salivary proteome, as well as the importance of sample preparation and processing techniques and their influence on downstream protein applications; post-translational modifications of salivary proteome and protein: protein interactions. In addition, we describe possible enrichment strategies for discerning post-translational modifications of salivary proteins, the potential utility of selected-reaction-monitoring techniques for biomarker discovery and validation, limitations to proteomics and the biomarker challenge and future perspectives. In summary, we provide recommendations for practical saliva sampling, processing and storage conditions to increase the quality of future studies in an emerging field of saliva clinical proteomics. We propose that the advent of technologies allowing sensitive and high throughput proteome-wide analyses, coupled to well-controlled study design, will allow saliva to enter clinical practice as an alternative to blood-based methods due to its simplistic nature of sampling, non-invasiveness, easy of collection and multiple collections by untrained professionals and cost-effective advantages.

Choice impulsivity: Definitions, measurement issues, and clinical implications

Background Impulsivity critically relates to many psychiatric disorders. Given the multifaceted construct that impulsivity represents, defining core aspects of impulsivity is vital for the assessment and understanding of clinical conditions. Choice impulsivity (CI), involving the preferential selection of smaller sooner rewards over larger later rewards, represents one important type of impulsivity. Method The International Society for Research on Impulsivity (InSRI) convened to discuss the definition and assessment of CI and provide recommendations regarding measurement across species. Results Commonly used preclinical and clinical CI behavioral tasks are described, and considerations for each task are provided to guide CI task selection. Differences in assessment of CI (self-report, behavioral) and calculating CI indices (e.g., area-under-the-curve, indifference point, steepness of discounting curve) are discussed along with properties of specific behavioral tasks used in preclinical and clinical settings. Conclusions The InSRI group recommends inclusion of measures of CI in human studies examining impulsivity. Animal studies examining impulsivity should also include assessments of CI and these measures should be harmonized in accordance with human studies of the disorders being modeled in the preclinical investigations. The choice of specific CI measures to be included should be based on the goals of the study and existing preclinical and clinical literature using established CI measures.

The visual and functional impacts of astigmatism and its clinical management

Purpose: To provide a comprehensive overview of research examining the impact of astigmatism on clinical and functional measures of vision, the short and longer term adaptations to astigmatism that occur in the visual system, and the currently available clinical options for the management of patients with astigmatism. Recent findings: The presence of astigmatism can lead to substantial reductions in visual performance in a variety of clinical vision measures and functional visual tasks. Recent evidence demonstrates that astigmatic blur results in short-term adaptations in the visual system that appear to reduce the perceived impact of astigmatism on vision. In the longer term, uncorrected astigmatism in childhood can also significantly impact on visual development, resulting in amblyopia. Astigmatism is also associated with the development of spherical refractive errors. Although the clinical correction of small magnitudes of astigmatism is relatively straightforward, the precise, reliable correction of astigmatism (particularly high astigmatism) can be challenging. A wide variety of refractive corrections are now available for the patient with astigmatism, including spectacle, contact lens and surgical options. Conclusion: Astigmatism is one of the most common refractive errors managed in clinical ophthalmic practice. The significant visual and functional impacts of astigmatism emphasise the importance of its reliable clinical management. With continued improvements in ocular measurement techniques and developments in a range of different refractive correction technologies, the future promises the potential for more precise and comprehensive correction options for astigmatic patients.

Clinical trials in pediatrics

“Children are not little adults.” Almost all aspects of children's health including clinical trials and drug development are poor cousins of adult health. Over the years, pediatricians worldwide caution against blind extrapolation of adult data to children as it may result in considerable harm [1,2]. Also, it is increasingly recognized that the roots of many chronic diseases in adulthood stem from childhood and tackling health issues in children lead to improved health in adults [3,4]. Furthermore, investment in early childhood has long-term benefits in adults not only in health but also in other aspects of life such as education and crime reduction [4,5]. Arguably, health at birth is the single most important predictor of health in adulthood as the inequality of an infant at birth has intergenerational effects [5]. The Carolina Abecedarian Project showed that early childhood programs that are of high quality result in substantial societal benefits (e.g., reduction of crime, increased earnings, better education) [4,5]. A recent publication from this project found that this benefit also translated into improved adult health outcomes [4]. In a randomized trial, Campbell and colleagues described that disadvantaged children who were randomized to the intervention group (early education, health screenings and nutrition program) had significantly lower rates of metabolic syndrome, obesity and hypertension, when aged in their mid-30s, compared with the control group [4]...

The relationship between emotional intelligence and depression in a clinical sample

Background and Objectives: Although depression is a commonly occurring mental illness, research concerning strategies for early detection and prophylaxis has not until now focused on the possible utility of measures of Emotional Intelligence (EI) as a potential predictive factor. The current study aimed to investigate the relationship between EI and a clinical diagnosis of depression in a cohort of adults. Methods: Sixty-two patients (59.70% female) with a DSM-IV-TR diagnosis of a major affective disorder and 39 aged matched controls (56.40% female) completed self-report instruments assessing EI and depression in a cross-sectional study. Results: Significant associations were observed between severity of depression and the EI dimensions of Emotional Management (r = -0.56) and Emotional Control (r = -0.62). The results show a reduced social involvement, an increased prior institutionalization and an increased incidence of "Schizophrenic Psychosis" and "Abnormal Personalities" in the sub-group of repeated admissions. Conclusions: Measures of EI may have predictive value in terms of early identification of those at risk for developing depression. The current study points to the potential value of conducting further studies of a prospective nature.

Treatment for gender dysphoria in children : the new legal, ethical and clinical landscape

- Gender dysphoria is a condition in which a child's subjectively felt identity and gender are not congruent with her or his biological sex. Because of this, the child suffers clinically significant distress or impairment in social functioning. - The Family Court of Australia has recently received an increasing number of applications seeking authorisation for the provision of hormones to treat gender dysphoria in children. - Some medical procedures and interventions performed on children are of such a grave nature that court authorisation must be obtained to render them lawful. These procedures are referred to as special medical procedures. - Hormonal therapy for the treatment of gender dysphoria in children is provided in two stages occurring years apart. Until recently, both stages of treatment were regarded by courts as special medical treatments, meaning court authorisation had to be provided for both stages. - In a significant recent development, courts have drawn a distinction between the two stages of treatment, permitting parents to consent to the first stage. In addition, it has been held that a child who is determined by a court to be Gillick competent can consent to stage 2 treatment. - The new legal developments concerning treatment for gender dysphoria are of ethical, clinical and practical importance to children and their families, and to medical practitioners treating children with gender dysphoria. Medical practitioners should benefit from an understanding of the recent developments in legal principles. This will ensure that they have up-to-date information about the circumstances under which treatment may be conducted with parental consent, and those in which they must seek court authorisation.

Developing and evaluating interventions that are applicable and relevant to inpatients and those who care for them; a multiphase, pragmatic action research approach

Background Randomised controlled trials may be of limited use to evaluate the multidisciplinary and multimodal interventions required to effectively treat complex patients in routine clinical practice; pragmatic action research approaches may provide a suitable alternative. Methods A multiphase, pragmatic, action research based approach was developed to identify and overcome barriers to nutritional care in patients admitted to a metropolitan hospital hip-fracture unit. Results Four sequential action research cycles built upon baseline data including 614 acute hip-fracture inpatients and 30 purposefully sampled clinicians. Reports from Phase I identified barriers to nutrition screening and assessment. Phase II reported post-fracture protein-energy intakes and intake barriers. Phase III built on earlier results; an explanatory mixed-methods study expanded and explored additional barriers and facilitators to nutritional care. Subsequent changes to routine clinical practice were developed and implemented by the treating team between Phase III and IV. These were implemented as a new multidisciplinary, multimodal nutritional model of care. A quasi-experimental controlled, ‘before-and-after’ study was then used to compare the new model of care with an individualised nutritional care model. Engagement of the multidisciplinary team in a multiphase, pragmatic action research intervention doubled energy and protein intakes, tripled return home discharge rates, and effected a 75% reduction in nutritional deterioration during admission in a reflective cohort of hip-fracture inpatients. Conclusions This approach allowed research to be conducted as part of routine clinical practice, captured a more representative patient cohort than previously reported studies, and facilitated exploration of barriers and engagement of the multidisciplinary healthcare workers to identify and implement practical solutions. This study demonstrates substantially different findings to those previously reported, and is the first to demonstrate that multidisciplinary, multimodal nutrition care reduces intake barriers, delivers a higher proportional increase in protein and energy intake compared with baseline than other published intervention studies, and improves patient outcomes when compared with individualised nutrition care. The findings are considered highly relevant to clinical practice and have high translation validity. The authors strongly encourage the development of similar study designs to investigate complex health problems in elderly, multi-morbid patient populations as a way to evaluate and change clinical practice.

Clinical use of diodes and micro-chambers to obtain accurate small field output factor measurements

There have been substantial advances in small field dosimetry techniques and technologies, over the last decade, which have dramatically improved the achievable accuracy of small field dose measurements. This educational note aims to help radiation oncology medical physicists to apply some of these advances in clinical practice. The evaluation of a set of small field output factors (total scatter factors) is used to exemplify a detailed measurement and simulation procedure and as a basis for discussing the possible effects of simplifying that procedure. Field output factors were measured with an unshielded diode and a micro-ionisation chamber, at the centre of a set of square fields defined by a micro-multileaf collimator. Nominal field sizes investigated ranged from 6×6 to 98×98 mm2. Diode measurements in fields smaller than 30 mm across were corrected using response factors calculated using Monte Carlo simulations of the full diode geometry and daisy-chained to match micro-chamber measurements at intermediate field sizes. Diode measurements in fields smaller than 15 mm across were repeated twelve times over three separate measurement sessions, to evaluate the to evaluate the reproducibility of the radiation field size and its correspondence with the nominal field size. The five readings that contributed to each measurement on each day varied by up to 0.26%, for the “very small” fields smaller than 15 mm, and 0.18% for the fields larger than 15 mm. The diode response factors calculated for the unshielded diode agreed with previously published results, within 1.6%. The measured dimensions of the very small fields differed by up to 0.3 mm, across the different measurement sessions, contributing an uncertainty of up to 1.2% to the very small field output factors. The overall uncertainties in the field output factors were 1.8% for the very small fields and 1.1% for the fields larger than 15 mm across. Recommended steps for acquiring small field output factor measurements for use in radiotherapy treatment planning system beam configuration data are provided.

Research on injury compensation and health outcomes : ignoring the problem of reverse causality led to a biased conclusion

Objective This study highlights the serious consequences of ignoring reverse causality bias in studies on compensation-related factors and health outcomes and demonstrates a technique for resolving this problem of observational data. Study Design and Setting Data from an English longitudinal study on factors, including claims for compensation, associated with recovery from neck pain (whiplash) after rear-end collisions are used to demonstrate the potential for reverse causality bias. Although it is commonly believed that claiming compensation leads to worse recovery, it is also possible that poor recovery may lead to compensation claims—a point that is seldom considered and never addressed empirically. This pedagogical study compares the association between compensation claiming and recovery when reverse causality bias is ignored and when it is addressed, controlling for the same observable factors. Results When reverse causality is ignored, claimants appear to have a worse recovery than nonclaimants; however, when reverse causality bias is addressed, claiming compensation appears to have a beneficial effect on recovery, ceteris paribus. Conclusion To avert biased policy and judicial decisions that might inadvertently disadvantage people with compensable injuries, there is an urgent need for researchers to address reverse causality bias in studies on compensation-related factors and health.

Oncology service initiatives and research in regional Australia

Objective: This paper reflects on the recent growth of cancer research being conducted through some of Australia’s rural centres. It encompasses work being done across the fields of clinical, translational and health services research. Design: This is a collaborative piece with contributions from rural health researchers, clinical and cancer services staff from several different regions. Conclusion: The past decade has seen an expansion in cancer research in rural and regional Australia driven in part by the recognition that cancer patients in remote areas experience poorer outcomes than their metropolitan counterparts. This work has led to the development of more effective cancer networks and new models of care designed to meet the particular needs of the rural cancer patient. It is hoped that the growth of cancer research in regional centres will, in time, reduce the disparity between rural and urban communities and improve outcomes for cancer patients across both populations.

Sharing of clinical data in a maternity setting: How do paper hand-held records and electronic health records compare for completeness?

Background Historically, the paper hand-held record (PHR) has been used for sharing information between hospital clinicians, general practitioners and pregnant women in a maternity shared-care environment. Recently in alignment with a National e-health agenda, an electronic health record (EHR) was introduced at an Australian tertiary maternity service to replace the PHR for collection and transfer of data. The aim of this study was to examine and compare the completeness of clinical data collected in a PHR and an EHR. Methods We undertook a comparative cohort design study to determine differences in completeness between data collected from maternity records in two phases. Phase 1 data were collected from the PHR and Phase 2 data from the EHR. Records were compared for completeness of best practice variables collected The primary outcome was the presence of best practice variables and the secondary outcomes were the differences in individual variables between the records. Results Ninety-four percent of paper medical charts were available in Phase 1 and 100% of records from an obstetric database in Phase 2. No PHR or EHR had a complete dataset of best practice variables. The variables with significant improvement in completeness of data documented in the EHR, compared with the PHR, were urine culture, glucose tolerance test, nuchal screening, morphology scans, folic acid advice, tobacco smoking, illicit drug assessment and domestic violence assessment (p = 0.001). Additionally the documentation of immunisations (pertussis, hepatitis B, varicella, fluvax) were markedly improved in the EHR (p = 0.001). The variables of blood pressure, proteinuria, blood group, antibody, rubella and syphilis status, showed no significant differences in completeness of recording. Conclusion This is the first paper to report on the comparison of clinical data collected on a PHR and EHR in a maternity shared-care setting. The use of an EHR demonstrated significant improvements to the collection of best practice variables. Additionally, the data in an EHR were more available to relevant clinical staff with the appropriate log-in and more easily retrieved than from the PHR. This study contributes to an under-researched area of determining data quality collected in patient records.

Environmental conditions are important for establishing and evaluating pre-clinical models of GVHD

GVHD remains the major complication of allo-HSCT. Murine models are the primary system used to understand GVHD, and to develop potential therapies. Several factors are critical for GVHD in these models; including histo- compatibility, conditioning regimen, and T-cell number. We serendipitously found that environmental factors such as the caging system and bedding also significantly impact the kinetics of GVHD in these models. This is important because such factors may influence the experimental conditions required to cause GVHD and how mice respond to various treatments. Consequently, this is likely to alter interpretation of results between research groups, and the perceived effectiveness of experimental therapies.

Data driven and practice-based evidence : design and development of efficient and effective clinical decision support system

Decision-making is such an integral aspect in health care routine that the ability to make the right decisions at crucial moments can lead to patient health improvements. Evidence-based practice, the paradigm used to make those informed decisions, relies on the use of current best evidence from systematic research such as randomized controlled trials. Limitations of the outcomes from randomized controlled trials (RCT), such as “quantity” and “quality” of evidence generated, has lowered healthcare professionals’ confidence in using EBP. An alternate paradigm of Practice-Based Evidence has evolved with the key being evidence drawn from practice settings. Through the use of health information technology, electronic health records (EHR) capture relevant clinical practice “evidence”. A data-driven approach is proposed to capitalize on the benefits of EHR. The issues of data privacy, security and integrity are diminished by an information accountability concept. Data warehouse architecture completes the data-driven approach by integrating health data from multi-source systems, unique within the healthcare environment.

Importance of animal models in schizophrenia research

Objective This review aims to summarize the importance of animal models for research on psychiatric illnesses, particularly schizophrenia. Method and Results Several aspects of animal models are addressed, including animal experimentation ethics and theoretical considerations of different aspects of validity of animal models. A more specific discussion is included on two of the most widely used behavioural models, psychotropic drug-induced locomotor hyperactivity and prepulse inhibition, followed by comments on the difficulty of modelling negative symptoms of schizophrenia. Furthermore, we emphasize the impact of new developments in molecular biology and the generation of genetically modified mice, which have generated the concept of behavioural phenotyping. Conclusions Complex psychiatric illnesses, such as schizophrenia, cannot be exactly reproduced in species such as rats and mice. Nevertheless, by providing new information on the role of neurotransmitter systems and genes in behavioural function, animal 'models' can be an important tool in unravelling mechanisms involved in the symptoms and development of such illnesses, alongside approaches such as post-mortem studies, cognitive and psychophysiological studies, imaging and epidemiology.