Identification of Genetic and Genomic Influences on Progressive Ethanol Consumption in Diversity Outbred Mice.

Genetic factors play a significant role in the risk for development of alcohol use disorder (AUD). Using 3-bottle choice intermittent access ethanol (IEA), we have employed the Diversity Outbred (DO) mouse panel as a model of alcohol use disorder in a genetically diverse population. Through use of gene expression network analysis techniques, in combination with expression quantitative trait loci (eQTL) mapping, we have completed an extensive analysis of the influence of genetic background on gene expression changes in the prefrontal cortex (PFC). This approach revealed that, in DO mice, genes whose expression was significantly disrupted by intermittent ethanol in the PFC also tended to be those whose expression correlated to intake. This finding is in contrast to previous studies of both mice and nonhuman primates. Importantly, these analyses identified genes involved in myelination in the PFC as significantly disrupted by IEA, correlated to ethanol intake, and having significant eQTLs. Genes that code for canonical components of the myelin sheath, such as Mbp, also emerged as key drivers of the gene expression response to intermittent ethanol drinking. Several regulators of myelination were also key drivers of gene expression, and had significant QTLs, indicating that genetic background may play an important role in regulation of brain myelination. These findings underscore the importance of disruption of normal myelination in the PFC in response to prolonged ethanol exposure, that genetic variation plays an important role in this response, and that this interaction between genetics and myelin disruption in the presence of ethanol may underlie previously observed behavioral changes under intermittent access ethanol drinking such as escalation of consumption.

An integrated knowledge translation approach to develop a shared decision-making strategy for use by Inuit in cancer care: a qualitative study.

Background: In relation to the general Canadian population, Inuit face increased cancer risks and barriers to health services use. In shared decision-making (sdm), health care providers and patients make health care decisions together. Enhanced participation in cancer care decisions is a need for Inuit. Integrated knowledge translation (kt) supports the development of research evidence that is likely to be patient-centred and applied in practice. Objective: Using an integrated kt approach, we set out to promote the use of sdm by Inuit in cancer care. Methods: An integrated kt study involving researchers with a Steering Committee of cancer care system partners who support Inuit in cancer care ("the team") consisted of 2 theory-driven phases:■ using consensus-building methods to tailor a previously developed sdm strategy and developing training in the sdm strategy; and■ training community support workers (csws) in the sdm strategy and testing the sdm strategy with community members. Results: The team developed a sdm strategy that included a workshop and a booklet with 6 questions for use by csws with patients. The sdm strategy (training and booklet) was finalized based on feedback from 5 urban-based Inuit csws who were recruited and trained in using the strategy. Trained csws were matched with 8 community members, and use of the sdm strategy was assessed during interviews, reported as 6 themes. Participants found the sdm strategy to be useful and feasible for use. Conclusions: An integrated kt approach of structured research processes with partners developed a sdm strategy for use by Inuit in cancer care. Further work is needed to test the sdm strategy.

Metabolic syndrome, dyslipidemia and prostate cancer recurrence after primary surgery or radiation in a veterans cohort.

BACKGROUND: Metabolic syndrome (MetS) has been hypothesized to be associated with cancer, including prostate cancer (PCa), but the relationship is not well characterized. We analyze the relationship between MetS features and localized PCa recurrence after treatment. METHODS: Men having primary treatment for localized PCa were included from a multi-site regional veteran network. Recurrence was defined as nadir PSA +2 ng ml(-1) (radiation) or PSA⩾0.2 ng ml(-1) (prostatectomy). MetS was based on consensus professional society guidelines from the American Heart Association and International Diabetes Federation (three of: hypertension >130/85 mm Hg, fasting blood glucose ⩾100 mg dl(-1), waist circumference >102 cm, high-density lipoprotein <40 mg dl(-1), triglycerides ⩾150 mg dl(-1)). Closely related abnormality in low-density lipoprotein (LDL; >130 mg dl(-1)) was also examined. Analysis of PCa recurrence risk included multivariable Cox proportional hazards regression with propensity adjustment. RESULTS: Of the 1706 eligible men, 279 experienced recurrence over a median follow-up period of 41 months (range 1-120 months). Adjustment variables associated with PCa recurrence included: index PSA, Gleason, and tumor stage. Independent variables of interest associated with PCa recurrence were hyperglycemia and elevated LDL. Elevated LDL was associated with PCa recurrence (multivariable hazard ratio (HR) 1.34, 95% confidence interval (CI) 1.03, 1.74; propensity adjusted HR 1.33, 95% CI 1.03, 1.72). There was also an association between impaired fasting glucose and PCa recurrence in (multivariable HR 1.54, 95% CI 1.10, 2.15; propensity adjusted HR 1.41, 95% CI 1.01, 1.95). MetS was not associated with PCa recurrence (multivariable: HR 0.96, 95% CI 0.61, 1.50; propensity adjusted HR 1.04, 95% CI 0.67, 1.62). CONCLUSIONS: PCa recurrence is not associated with MetS but is associated with elevated LDL and impaired fasting glucose. If confirmed, these data may help provide modifiable targets in preventing recurrence of PCa.

Diagnostic utility of the Quick Inventory of Depressive Symptomatology (QIDS-C16 and QIDS-SR16) in the elderly.

OBJECTIVE: To evaluate psychometric properties and comparability ability of the Montgomery-Asberg Depression Rating Scale (MADRS) vs. the Quick Inventory of Depressive Symptomatology-Clinician-rated (QIDS-C(16)) and Self-report (QIDS-SR(16)) scales to detect a current major depressive episode in the elderly. METHOD: Community and clinic subjects (age >or=60 years) were administered the Mini-International Neuropsychiatric Interview (MINI) for DSM-IV and three depression scales randomly. Statistics included classical test and Samejima item response theories, factor analyzes, and receiver operating characteristic methods. RESULTS: In 229 elderly patients (mean age = 73 years, 39% male, 54% current depression), all three scales were unidimensional and with nearly equal Cronbach alpha reliability (0.85-0.89). Each scale discriminated persons with major depression from the non-depressed, but the QIDS-C(16) was slightly more accurate. CONCLUSION: All three tests are valid for detecting geriatric major depression with the QIDS-C(16) being slightly better. Self-rated QIDS-SR(16) is recommended as a screening tool as it is least expensive and least time consuming.

A comparative study of the performance of individuals with fragile X syndrome and Fmr1 knockout mice on Hebb-Williams mazes.

Fragile X syndrome (FXS) is the most prevalent form of heritable mental retardation. It arises from a mutation in the FMR1 gene on the X chromosome that interferes with expression of fragile X mental retardation protein (FMRP) and leads to a wide range of behavioural and cognitive deficits. Previous studies have shown a deficit in basic visual perceptual processing as well as spatial abilities in FXS. How such a deficit may impact spatial navigation remains unknown. The current study extended previous research by evaluating spatial learning and memory using both virtual and physical versions of Hebb-Williams mazes, which allows for testing of humans and animals under comparable conditions. We compared the performance of individuals affected by FXS to typically developing individuals of equivalent mental age as well as the performance of Fmr1 knockout mice to wild-type control mice on the same maze problems. In human participants, performance of the comparison group improved across trials, showing expected significant decreases in both errors and latency. In contrast, the performance of the fragile X group remained at similar levels across trials. Although wild-type control mice made significantly fewer errors than the Fmr1 knockout mice, latencies were not statistically different between the groups. These findings suggest that affected humans and mice show similar spatial learning deficits attributable to the lack of FMRP. The implications of these data are discussed including the notion that Hebb-Williams mazes may represent a useful tool to examine the impact of pharmacological interventions on mitigating or reversing the symptoms associated with FXS.

Assessing psychological well-being: a holistic investigation of NHS employees.

A substantial body of research has investigated the effects of work on the psychological well-being of employees. However, there has been little assessment of the ways in which workplace factors (such as job demands, working conditions, inter-personal relations and workplace change) interact with personal factors (such as work-life balance, family circumstances, key personality traits or demographic characteristics) to affect psychological health. This article reports findings from a study which aimed to construct and test a comprehensive model of the influences on employee well-being within the UK National Health Service (NHS). The results show that psychological well-being is influenced by a complex array of personal, environmental and work factors. A key finding is that there are clear associations between workplace change and well-being and between work-life (im)balance and well-being. These effects appear to be independent of one another and therefore require separate attention from managers and employers.

Symptom cluster associated with mild traumatic brain injury in university students.

There is growing recognition that even a minor blow to the head can have serious consequences on physical, cognitive, behavioral, and social well-being. Previous studies have indicated that such changes may in turn have a dramatic effect on the ability of university students to carry out their studies. This survey measured the prevalence of mild traumatic brain injury in a nonclinical population of 1,075 university students from all disciplines. In addition to surveying the nature, cause, and sex distribution, it further investigated the relationships between the physical, cognitive, behavioral, and social repercussions of the incidents. Results replicated earlier findings and indicated a prevalence rate of mild traumatic brain injury of 34.9% (n = 375). Moreover, significant correlations were found among the physical, cognitive, behavioral, and social changes reported by the students, suggesting a cluster of symptoms associated with such incidents. Altogether, these results suggest that even currently enrolled and active university students may face unique and subtle challenges related to a mild traumatic brain injury.

Does general practitioner involvement in commissioning maternity care make a difference?

OBJECTIVES: To evaluate the impact of general practitioners' commissioning of maternity services on women's experiences of care and on resource use, and to consider the implications for primary care commissioning. METHOD: Comparison of women's experiences and resource use between 11 commissioning and 10 non-commissioning general practices. Face-to-face interviews with 212 staff in general practices, National Health Service trusts and health authorities between 1996 and 1998 to establish how maternity care was organised. Women's experience of information, choice, control and resource use obtained by questionnaire mailed 4 weeks post-partum. Data were analysed using multi-level modelling to adjust for case-mix differences. RESULTS: After two reminders, 1957 women (62%) responded to the questionnaire (inter-practice range 52-81%). There were no significant differences in women's experience of care or their resource use between commissioning and non-commissioning practices. Commissioning practices were more likely to be associated with more vertically integrated models of service organisation, but responses to only three of 21 questions about experience of information, choice and control over care, or about resource use, differed between the four models of service organisation identified. CONCLUSIONS: The expectation that giving primary care organisations responsibility for commissioning care will result in improved patients' experiences of care or better use of resources should be treated with caution. The presence of strong national policy may be equally important. Models of service organisation are not proxies for quality of care. The most powerful force shaping patients' experiences of care may be health care professionals' ability to translate national policy into local services.

A review of an outpatient paediatric mental health clinic: what we did and what parents thought of it.

OBJECTIVE: To describe the work of a paediatric mental health (PMH) clinic in terms of the types of clients seen and the nature and intensity of interventions used. Also to survey the opinions of parents on issues such as helpfulness and effectiveness, and to tap into issues relating to acceptability and relevance. DESIGN: Retrospective review of case notes covering a one year period and postal client satisfaction questionnaire. SETTING: Children's wing of a large general hospital. SUBJECTS: The case notes of the 54 children referred were analysed. Postal questionnaires were sent to 53 parents of the 41 children who were treated over the targeted 12 months plus a further 12 families who were treated in the six months following. RESULTS: Forty one children with a broad range of paediatric difficulties were treated with their parents. Families were seen relatively promptly after referral and interventions were typically brief involving advice and counselling for parents and most commonly behavioural work with children. The results from the parent satisfaction questionnaire suggested that despite some initial wariness and uncertainty, parents found the clinic to be helpful. A small, but non significant decrease in rated symptom severity was found following treatment, but even in those cases where symptoms persisted or increased, parents still tended to report their experience as being helpful and from their comments seemed to value the clinic. Although parents seemed somewhat intimidated and uncertain of its relevance before attending, their comments suggested that they had benefited from talking about their child's difficulties and gaining understanding within a supportive and friendly environment. CONCLUSIONS: The PMH clinic was found to provide a brief, focused intervention for children and their families which was regarded as helpful by parents, even when the outcome was not necessarily a reduction in symptom severity.

Control cognitions and psychological disturbance in people with contrasting physically disabling conditions.

PURPOSE: This study examines the role of control cognitions, i.e. locus of control (LOC), in predicting adaptation to two contrasting physically disabling conditions. METHOD: Locus of control beliefs were investigated in terms of their relationship with psychological distress (anxiety and depression) experienced by people facing either spinal cord injury (SCI) or multiple sclerosis (MS). The role of pain experience was also considered in terms of its impact on psychological distress in both groups. RESULTS: Results indicated that although SCI subjects were more internally oriented than MS subjects, internality was not linked to lower levels of depression or anxiety in either group, although within the SCI group an external LOC was associated with increased depression and physical disability. CONCLUSIONS: For people facing a future with the challenge of physical disability, the pattern of progression of disability over time may be of significance in the development of psychological distress.

How Prepared is Prepared Enough?

A 17-year-old female was in the final stage in treatment of right unilateral cleft lip and palate. She had undergone a number of previous surgeries. Hearing and speech were good on evaluation, and her social and family situation were deemed excellent. After preparatory orthodontics she underwent a Lefort I maxillary advancement. Surgery was successful and she was admitted into postoperative recovery. However, the lack of adequate preoperative preparation caused traumatic reaction from the patient and her parents: anxiety over appearance, crying, refusal of oral fluids and oral care, refusal of analgesia, and refusal to mobilize. The patience and persistence of hospital staff slowly overcame all adversities and the patient moved on to full and successful recovery, but this case prompted changes in preoperative procedures and involvement of patients and their families in postoperative meal selection, planing, and preparation.

Evaluation of client and staff satisfaction with a Goal Planning project implemented with people with spinal cord injuries.

This study assesses client satisfaction and canvasses staff opinions concerning the first year of a Goal Planning rehabilitation programme implemented with in-patients who had sustained a severe spinal cord injury. Questionnaires were completed by 33 patients. As a keyworker system is an integral part of Goal Planning, separate questionnaires were completed by 13 staff/keyworkers. The results indicated that patients believed Goal Planning to be informative about their injury and helpful in promoting a sense of control over their rehabilitation. In addition, a positive, and statistically significant association was found between perceived informativeness and control and the implications for successful rehabilitation are considered. Staff also gave favourable feedback regarding the perceived benefits of Goal Planning for patients, relatives and staff, although they acknowledged the resulting increase in their workload.

The length of the referral chain after failing preschool tympanometry.

AIMS: To describe the time intervals during the process of detection and management of chronic secretory otitis media/glue ear. METHOD: Tympanometry records of 508 preschool children who failed both tympanometry screening and the subsequent retest were examined. Additional information was obtained from 205 parents/caregivers by telephone interview. RESULTS: Calculations of time intervals between tympanometry screening and retesting showed that 75% of children had been retested within 20 weeks and 95% by 40 weeks. Two-thirds (67%) of children had visited their general practitioner within 4 weeks of failing their retest, although 13% had still yet to be seen by 20 weeks. The mean time interval between the initial general practitioner visit and subsequently being seen by an ENT specialist was 20 weeks in the public system compared to 5 weeks if seen privately (p < 0.001). CONCLUSION: The preschool tympanometry screening programme functioned well, although there were delays in retesting 25% of preschoolers. There were substantial time intervals for some children for each link in the referral chain. The reasons for these delays needs investigation to determine how much it is a part of the treatment process and how much due to waiting list problems.