A guide on gene prioritization in studies of psychiatric disorders

There has been an increasing interest in the identification of genetic variants causing individual differences in human behavior. Psychiatrists have contributed to the genetics field by defining the most important behavioral characteristics and by studying the association between genetic variants and behavioral differences within phenotypically well‐characterized samples in which detailed assessments have been collected (e.g. neuroimaging). These samples are typically limited in size and are therefore not suitable for a genome‐wide association analysis. Instead, gene association studies conducted in such samples typically focus on a few genes of interest, allowing smaller sample sizes. However, the selection of high‐priority genes is not always straightforward and psychiatrists will usually have a limited background in genetics. We aim to fill this gap by (i) providing a basic introduction to genetics; (ii) showing how the selection of genes of interest can be optimized by the use of two web tools: Polysearch and Gene Prospector; (iii) illustrating how statistical power analyses can be performed and discussing the importance of sufficiently powered studies. This guide can help psychiatrists with limited experience in genetics in designing genetic studies that allow identification of specific behavioral, cognitive, or neural correlates of genetic risk variants, while avoiding common pitfalls. Copyright © 2015 John Wiley & Sons, Ltd.     

Community psychiatric nurse caseloads and the ‘worried well’: misspent time or vital work?

Community psychiatric nurses (CPNs) in the United Kingdom are being repeatedly urged to focus their attention upon those with serious and enduring psychotic illnesses, and to withdraw from working with the 'worried well' in the primary health care setting. In view of this pressure, it is important to discover the nature of community psychiatric nurses' non-psychotic caseloads. The aim of this study was to describe these cases, what precipitated their referral, what problems they suffered from, what effects these problems had upon their lives and what kinds of therapeutic interventions they were receiving. A random sample was drawn of non-psychotic CPN patients. The community psychiatric nurses then received a structured interview about the history, care and treatment of these patients. These patients did not, in general, suffer from minor, self-limiting conditions. They typically had had 5 years of contact with psychiatric services, and their psychiatric symptoms blighted their occupational, social and personal lives. Their condition caused significant carer burden, and there was frequently a risk of suicide. The CPNs case-managed a complex combination of interventions for these patients, of which psychotherapeutic methods were only one part. The findings show that community psychiatric nurses have a valid role to play in the care of those with non-psychotic mental disorders, and should continue to receive the opportunity, and appropriate training, to do so.     

Psychometric properties of the self‐sufficiency matrix among homeless and vulnerably housed individuals and families

Homeless service systems have been implementing assessment tools to inform service provision for individuals and families. Although a variety of assessments are available, their psychometric evidence base is limited. The self‐sufficiency matrix (SSM) is one assessment that demonstrates promising reliability and validity. However, the SSM's factor structure has been inconsistent across studies. This study explored the factor structure of the SSM, using exploratory factor analysis and confirmatory factor analysis in a sample of individuals (N = 427) and families ( N = 428) at risk of or experiencing homelessness. Data were derived from a midwestern city's Homeless Management Information System and included all participants from the Homelessness Prevention and Rapid Re‐Housing Program. Results suggest the SSM is multidimensional and the factor structure differs across individuals and families. Additionally, the SSM demonstrates measurement invariance across racial and gender groups. Further development and testing of the SSM is necessary to better serve individuals experiencing homelessness.     

Discovery of thiazostatin siderphores from Streptomyces sp. HMU0027 with a genomic DNA-based PCR assay targeting nonribosomal peptide synthetase

Nonribosomal peptides (NRPs) represent a large family of natural products with great diversities of chemical structures and biological activities. The peptide backbones of NRPs are synthesized by nonribosomal peptide synthetases (NRPSs) that minimally consist of one adenylation (A) domain, one peptidyl carrier protein (PCP) and one condensation (C) domain. In this study, we carried out a PCR screening and identified 21 “positive” strains from 100 actinomycete strains with the degenerate primers designed from the conserved sequences of A domains of NRPSs. One of the 21 “positive” strains, Streptomyces sp. HMU0027, was selected for large-scale fermentation (9 L) based on HPLC analysis, and subsequent isolation and structural elucidation afforded seven NRPS-synthesized thiazostatin siderophore analogues (1–7).Compound 1 was a new compound containing an unusual linkage between a phenolate siderophore and a sugar moiety. These results laid the foundation for further biosynthetic research of these thiazostatin analogues and highlighted the power of genome mining technologies based on biosynthetic knowledge in NRP discovery.     

Guided self diagnosis: an innovative approach to triage for emergency dental care

BACKGROUND: The basic model of triage, developed more than 200 years ago by the French, is based on categorization of patient needs and thus the urgency and time required for care. This model in various forms is used in most hospitals throughout the world. METHODS: In this study, a fully computerized guided self-diagnosis system (based on a neural network design) was designed, prototyped, developed and trialled by front line non-clinically trained personnel in emergency dentistry. RESULTS: A total of 699 patients were seen as a result of the triage assessment within 14 days of their initial phone call and/or first contact. Patients categorized as requiring care on the day (Category 1) were provided more items of care (50 per cent of all items) and the greatest number of extractions (76 per cent) and endodontic treatments (78 per cent). Other categories were found to require less urgent care. CONCLUSIONS: The triage system developed in this study clearly holds significant promise in reducing the impact of emergency dental patients on dental health care systems. However, it is recognized that the system still requires some adjustment to ensure all Category 1 patients are examined before less urgent categories.     

How to incorporate geriatric assessment in clinical decision-making for older patients with cancer. An implementation study

IntroductionWith the accumulating evidence on the added value on prediction of outcomes of geriatric assessment (GA) in older patients with cancer, the question shifts from whether performing a GA is useful, to how to implement this into standard practice in a feasible and effective way. The effect of implementing GA, and assessment of patient preferences on treatment recommendations by an onco-geriatric multidisciplinary team (MDT), was compared to the recommendation previously made by the tumor board (care as usual).MethodsPatients aged 70 years and older with a solid malignancy who were referred to a tertiary care center for diagnosis and treatment recommendations, as provided by a tumor board, were included. The intervention consisted of: a nurse-led GA and assessment of patient preferences prior to the start of oncological treatment, discussing this in an onco-geriatric MDT, and weighing all this information in a structured, stepwise manner. Treatment recommendations formulated by this onco-geriatric MDT were compared to the treatment recommendations by the tumor board.ResultsOf 236 eligible patients, 197 were included. For 27%, treatment recommendations from the onco-geriatric MDT differed from the recommendations formulated by the tumor board. These modifications were mostly towards less intensive curative or palliative treatment. Thirteen percent of patients were subsequently referred to a geriatrician in order to reach a treatment recommendation.DiscussionImplementing an onco-geriatric care trajectory, using GA and assessment of patient preferences, resulted in an adjustment of treatment recommendations for a quarter of patients. Thirteen percent needed subsequent referral to a geriatrician.     

Clinicians' reported use of clinical priority assessment criteria and their attitudes to prioritization for elective surgery: a cross-sectional survey

OBJECTIVES: To explore the attitudes of clinicians working in New Zealand publicly funded hospitals towards prioritizing patients for elective surgery, and their reported use of clinical priority assessment criteria (CPAC). DESIGN: A cross-sectional study using a postal questionnaire. The questionnaire drew on themes identified from an earlier qualitative study. Questions were closed and information was sought about perceptions of the need to prioritize patients, effective ways of doing so and the use of CPAC. SETTING: New Zealand. PARTICIPANTS: A national sample of cardiologists, cardiac, general and orthopaedic surgeons, and registrars. RESULTS: Three hundred and thirty-two clinicians responded to the survey (74.1%). Respondents generally agreed that a nationally consistent method of prioritizing patients for surgery was required but felt their clinical judgement was the most effective way of prioritizing patients. Current CPAC were considered to be administrative tools and there was marked variation in their reported use. Consistent use of CPAC using the constructs provided was more likely to be reported by cardiac specialists than general or orthopaedic surgeons. Other features of the hospital system in which surgeons worked also had a major impact on access to elective surgery. CONCLUSIONS: Clinicians recognized the need for a nationally consistent method of prioritizing patients. Although most did not consider current CPAC were effective in achieving this, many felt there was some potential in further development of tools. However, further development is problematic in the absence of objective measures of need and ability to benefit.     

Determination of national pediatric injury prevention priorities using the Injury Prevention Priority Score

Purpose

Previous studies have found that the Injury Prevention Priority Score (IPPS) provides a reliable and valid method to gauge the relative importance of different injury causal mechanisms at individual trauma centers. This study examines its applicability to prioritizing injury mechanisms on a national level and within defined pediatric age groups.

Methods

A total of 47,158 patients (age <17) in the National Pediatric Trauma Registry were grouped into common injury mechanisms based on ICD-9 E-Codes. Patients also were stratified by age group. IPPS was calculated for each mechanism and within each age group.

Results

Falls of all types account for the greatest number of injuries (n = 15,042; 32%), whereas child abuse results in the most severe injuries (mean Injury Severity Score, 13.3) However, the most significant mechanisms of injury, according to IPPS, were motor vehicle crashes followed by pedestrian struck by motor vehicles. Certain age groups had specific injury problems including child abuse in infants and assault and gun injuries in adolescents.

Conclusions

IPPS provides an objective, quantitative method for determining injury prevention priorities based on both frequency and severity at the national level. It also is sensitive to age-related changes in different mechanisms of injury.