Measuring high-risk parents' opinions about direct-to-consumer genetic testing for adult-onset inherited cancer syndromes in their adolescent and young adult children.

Neither direct-to-consumer (DTC) genetic testing nor predictive genetic testing for adult-onset conditions is recommended for minor children due to ethical concerns and low clinical utility. However, parents with pathogenic variants (PVs) in disease-causing genes may be interested in pursuing genetic testing that includes the familial PV for their children. The Pediatric Testing Attitudes Scale (P-TAS) was previously developed to examine high-risk parents' opinions about pediatric BRCA genetic testing for adult-onset breast/ovarian cancer. Here, the psychometric properties of the P-TAS were examined in a new sample of N = 126 parents (M age = 47.2 years) with PVs in a more complete set of cancer risk genes represented on DTC panel tests. The mean score on the P-TAS was 44 out of a maximum score of 60, indicating that a majority of parents generally held favorable opinions about testing their children for adult-onset inherited cancer syndromes. The internal consistency of the full scale was high (α = 0.91). A factor analysis identified two-component scales, labeled Attitudes and Beliefs (α = 0.93) and Decision Making and Communication (α = 0.83). In a multivariable regression model, P-TAS co-factors accounted for 34% of variance in parental opinions, including the frequency of prior family communication about cancer and the likelihood of utilizing DTC genetic testing with children (R2  = 0.34, p < 0.001). Results suggest that the P-TAS remains a reliable measure to assess high-risk parents' opinions about pediatric DTC genetic testing for adult-onset conditions, with promising validity. Applications of the P-TAS include informing genetic counseling practice, pediatric medical care, and policy guidelines surrounding DTC genetic testing.

Facilitating a Major Staffing Transition in a State Psychiatric Hospital With Changes to Nursing Orientation.

BACKGROUND: A large state psychiatric hospital experienced a state-mandated Reduction in Force that resulted in the abrupt loss and rapid turnover of more than 40% of its nursing and paraprofessional staff. The change exemplified current national trends toward downsizing and facility closure. OBJECTIVE: This article describes revisions to the nursing orientation program that supported cost containment and fidelity to mission and clinical practices during the transition. DESIGN: An existing nursing orientation program was reconfigured in alignment with principles of rational instructional design and a core-competencies model of curriculum development, evidence-based practices that provided tactical clarity and commonality of purpose during a complex and emotionally charged transition period. RESULTS: Program redesign enabled efficiencies that facilitated the transition, with no evidence of associated negative effects. CONCLUSION: The process described here offers an example for hospitals facing similar workforce reorganization in an era of public sector downsizing.

Decision making in liver transplantation--limited application of the liver donor risk index.

The liver donor risk index (LDRI), originally developed in 2006 by Feng et al. and since modified, is a method of evaluating liver grafts from deceased donors through the determination of the relative risk of graft failure after transplantation. Online and paper surveys about attitudes and practices regarding decision making in liver transplantation and the role of the LDRI were sent to liver transplant physicians. One hundred forty-seven of 401 eligible respondents (37%) returned partial or complete surveys. The majority of the respondents were male (116/134 or 87%) and practiced in academic medical centers (128/138 or 93%). Transplant coordinators initially contacted the candidate with an offer in 81% of the programs. Eighty-eight of 143 respondents (62%) reported that they were very familiar with the LDRI, but the vast majority (114/137 or 83%) rarely or never discussed the concept of the LDRI with their patients. A majority of the respondents (96/132 or 73%) believed that the LDRI does not adequately describe a liver's relative risk of graft failure and that there are factors making the LDRI potentially misleading (122/138 or 88%). Nevertheless, 60 of 130 respondents (46%) believed that the LDRI would increase/improve shared decision making. The LDRI has not been widely adopted because of concerns that (1) it does not accurately reflect posttransplant survival, (2) it excludes relevant donor and recipient factors, and (3) it is too complicated for candidates to grasp. There is a need to improve it or to develop other decision-making tools to help promote shared decision making. There is also great diversity in how liver offers are made to ambulatory candidates and in how transplant programs address a candidate's refusal. Research is needed to determine evidence-based best practice.

Neurochemical and behavioral effects of chronic unpredictable stress.

Chronic stress can influence behaviors associated with medial prefrontal cortex (mPFC) function, such as cognition and emotion regulation. Dopamine in the mPFC is responsive to stress and modulates its behavioral effects. The current study tested whether exposure to 10 days of chronic unpredictable stress (CUS) altered the effects of acute elevation stress on dopamine release in the mPFC and on spatial recognition memory. Male rats previously exposed to CUS or nonstressed controls were tested behaviorally, underwent microdialysis to assess mPFC dopamine levels or underwent blood sampling for corticosterone analysis. Dopamine in the mPFC significantly increased in both groups during acute elevation stress compared with baseline levels, but the level was attenuated in CUS rats compared with controls. Control rats exposed to elevation stress immediately before the T-maze test showed impaired performance, whereas CUS rats did not. No group differences were observed in general motor activity or plasma corticosterone levels following elevation stress. The present results indicate that prior exposure to this CUS procedure reduced dopamine release in the mPFC during acute elevation stress and prevented the impairment of performance on a spatial recognition test following an acute stressor. These findings may contribute to an understanding of the complex behavioral consequences of stress.

The delayed effects of chronic unpredictable stress on anxiety measures.

Previous research has found that exposure to unpredictable stress can augment anxiety in humans and animals. The appearance of anxiety symptoms in humans frequently develop after stress exposure has terminated, but few rodent studies have systematically examined the delayed anxiogenic effects of unpredictable stress. Therefore, the current study investigated whether anxiety-like behaviors in rats would increase at several time intervals following exposure to chronic unpredictable stress (CUS). Unconditioned and conditioned response tasks were used to assess anxiety in male rats 1, 7 or 14 days following exposure to 10 days of a variety of stressors. Rats exposed to CUS showed increased burying behaviors and immobility during the defensive burying test, a conditioned anxiety test. The effects on burying behavior were apparent 7 and 14 days after the termination of the unpredictable stress procedure, but not when tested 1 day after CUS. Total time immobile in the defensive burying test also increased 14 days after termination of the last stressor. In contrast, there were no significant effects of CUS on behavioral measures in the unconditioned response tasks, the elevated plus-maze or light-dark box, at any time point following exposure to CUS. The current findings suggest that CUS may be a useful model of human conditioned anxiety that develops subsequent to chronic stress exposure.

The Advantages and Challenges of Testing Children for Heritable Predisposition to Cancer.

The increased application of germline genetic testing is expanding our understanding of the risk factors associated with childhood cancer development, and, in some cases, such testing is also informing clinical management. Nonetheless, the incorporation of genetic testing into the pediatric oncology setting is complex and associated with many ethical and practical challenges. The decision as to whether to pursue clinical genetic testing for hereditary cancer predisposition for children should always be guided by the best interest of the child. Despite this fundamental ethical principle, patients, parents, and health care providers may differ in their opinions. Clinical genetic testing to detect the presence of predisposition syndromes associated with childhood-onset cancers, particularly those for which surveillance and preventive measures have proven to enhance outcome, is currently well accepted. On the other hand, clinical genetic testing of children for syndromes associated with adult-onset cancers has raised many concerns about the potential for psychological harm and disrespect of patient autonomy. As a consequence, such testing is not encouraged. The challenges surrounding germline genetic testing are further complicated when testing is done in the research setting and/or when it involves whole-exome or whole-genome sequencing approaches, which can uncover genetic variants that may or may not be associated with the disease under study. Accordingly, there is great debate around these processes and the most appropriate approaches regarding the return of test results. Future research is needed to enhance knowledge about how best to incorporate genomic information into clinical practice.

Persistent behavioral and neurochemical sensitization to an acute injection of methamphetamine following unpredictable stress.

Prior research in humans and animals suggest that exposure to chronic stress alters the response to drugs of abuse, increasing vulnerability to drug addiction. Chronic unpredictable stress (CUS) has been shown to augment the increase of dopamine in the striatum when challenged with high doses of methamphetamine immediately following stress exposure, however it is not known whether this neurochemical stress-sensitization continues after the cessation of the stressors or if behavioral sensitization is also present. Therefore, the current study examined the immediate and delayed effects of CUS on methamphetamine-induced behaviors and striatal dopamine levels. Male rats were exposed to 10 days of CUS and then tested in either an open field box to assess locomotion or underwent in vivo microdialysis to measure striatal dopamine levels immediately following CUS or after a 1-2 week delay. All rats exposed to CUS showed a potentiated locomotor response immediately following an acute injection of 7.5mg/kg methamphetamine compared to non-stressed control rats. Both groups of CUS rats also showed augmented dopamine release and rectal temperatures following methamphetamine with prolonged increases in the CUS rats tested after a delay. These results suggest that CUS increases the sensitivity of a rat to a single injection of methamphetamine and that the increased sensitivity persists for up to 2 weeks following the last stressor.

Using structured clinical feedback to encourage alternatives to use of "P.R.N." medication in a state psychiatric hospital.

OBJECTIVE: The study examined whether reductions in the use of pro re nata (p.r.n.) psychotropic medications could be achieved in a large public-sector psychiatric hospital, without adverse behavioral consequences, by disseminating a database that tracks p.r.n. use to clinical teams. METHODS: A performance improvement project was implemented over 28 months, involving all 166 patients in one section of a state psychiatric hospital. A spread- sheet tracking p.r.n. administration for each patient was provided weekly to unit treatment teams. Clinical outcome monitoring focused on the number of p.r.n. administrations and on p.r.n. "events," defined as ≥ 3 multiple administrations per week and ≥ 10 per month. Episodes of patient seclusion, restraint, and violent incidents were also monitored. RESULTS: From September 2008 to December 2010, with a stable patient population census, total monthly administrations of psychotropic p.r.n. medications decreased from 642 to 240; administrations of non-psychotropic "medical" p.r.n. agents also decreased, from 279 to 72. In year-by-year comparisons, significant decreases (P < 0.05) were observed in the total number of psychotropic and medical p.r.n. administrations, in weekly as well as monthly p.r.n. events, and in the number of patients receiving any p.r.n. administrations. There was no change from 2008 to 2010 in the number of violent incidents; the use of both seclusion and restraint decreased (P < 0.05). CONCLUSION: The findings suggest that p.r.n. use can be reduced safely through timely feedback of relevant clinical data.

Using compression calorimetry to characterize powder compaction behavior of pharmaceutical materials.

The process by which pharmaceutical powders are compressed into cohesive compacts or tablets has been studied using a compression calorimeter. Relating the various thermodynamic results to relevant physical processes has been emphasized. Work, heat, and internal energy change values have been determined with the compression calorimeter for common pharmaceutical materials. A framework of equations has been proposed relating the physical processes of friction, reversible deformation, irreversible deformation, and inter-particle bonding to the compression calorimetry values. The results indicate that irreversible deformation dominated many of the thermodynamic values, especially the net internal energy change following the compression-decompression cycle. The relationships between the net work and the net heat from the complete cycle were very clear indicators of predominating deformation mechanisms. Likewise, the ratio of energy stored as internal energy to the initial work input distinguished the materials according to their brittle or plastic deformation tendencies.