Effect of divalproex sodium on behavioural and cognitive problems in elderly dementia

BACKGROUND: Behavioural and psychological symptoms of dementia (BPSD) occur in up to 90% of individuals with dementia at some point in their illness. BPSD reduce patient quality of life, cause great distress to caregivers and are the most common reason for institutionalisation. In nursing homes, pharmacological measures (usually antipsychotics or benzodiazepines) are often required to control agitation and aggression in patients with dementia. However, no medications have been approved by the US Food and Drug Administration for this indication as yet. The antiepileptic agent divalproex sodium may have advantages in this setting because of lower rates of drug interactions and adverse effects in this patient population. OBJECTIVE: The aim of the study was to assess the impact of treatment with divalproex sodium on behavioural, mood and cognitive measures in a population of elderly nursing home residents with a history of behaviour problems associated with dementia. MATERIALS AND METHODS: The study was a retrospective analysis of a long-term care database which allowed assessment of the impact of divalproex sodium therapy on behavioural, mood and cognitive measures in elderly nursing home residents with a history of dementia-related behaviour problems. Minimum Data Set items relating to problems of behaviour, cognition and mood were collected prior to and after divalproex sodium treatment over a 1-year period. Two-phase generalised linear regression, with fixed intersections at the time of divalproex sodium initiation, was used to estimate trends in each measure prior to and after divalproex sodium initiation. Monotherapy, combination therapy with benzodiazepines and antipsychotics, and dose comparisons of divalproex sodium were studied. RESULTS: In all three situations (i.e. as monotherapy, in combination with benzodiazepines and antipsychotics, and at both higher and lower doses), divalproex sodium therapy was shown to have multiple beneficial effects on various behavioural, mood and cognition indicators in elderly nursing home residents. In general, the data seemed to support more favourable results for the higher divalproex sodium dose group. CONCLUSIONS: These data support the use of divalproex sodium in elderly nursing home residents with a history of dementia and behaviour problems and warrant conduct of prospective, randomised trials of the drug in this setting.     

A breast feeding education and promotion program: Effects on knowledge,attitudes, and support for breast feeding

This study was undertaken to determine the effects of a partner-support, incentive-baed educational program on breast feeding knowledge, attitudes and support and to examine the relationship between feeding intentions and feeding behavior among low-income women. Women who expressed a willingness to participate in the intervention were randomly assigned to intervention and usual breast feeding (control) groups. Sixty-eight primipara women, with expected due dates between May and December, 1992, volunteered to participate in the study. Of these, 34 were randomly assigned to each of the two groups. Approximately 81 percent of the women completed the study, leaving n=29 in the control group and n-26 in the intervention group. The intervention consisted of special incentives (prizes) for women and their partners to participate in several breast feeding education and promotion activities. Intervention group women and their partners experienced positive changes in breast feeding knowledge and attitudes. Furthermore, the intervention seemed to have influenced more women in the treatment group to breast feed despite their prenatal feeding intentions. In addition, the partners of intervention group women were perceived to be more supportive of, breast feeding than control group partners. These findings suggest that incentives, such as donated prizes, can be used to attract lower socioeconomic group women and their partners to breast feeding promotion interventions. Participation in such interventions can produce positive changes in breast feeding knowledge, attitudes, and support, and can have a dramatic effect in promoting breast feeding.This study was supported through contract no. 59-3198-1-050 from the Food and Nutrition Service, U.S. Department of Agriculture.     

Development and usability of a feedback tool, “My Personal Brain Health Dashboard”, to improve setting of self-management goals among people living with HIV in Canada

Quality of Life Research - (1) To develop a personalized health outcome profile as a feedback tool to improve self-management in people living with chronic conditions such as HIV and (2) to...     

Phase I and pharmacokinetic study of Bay 38-3441, a camptothecin glycoconjugate, administered as a 30-minute infusion daily for five days every 3 weeks in patients with advanced solid malignancies

Bay 38-3441 is a camptothecin glycoconjugate which stabilizes the active lactone form of camptothecin and allows selective uptake into tumor cells. We conducted a phase I study of Bay 38-3441 administered as a 30-minute infusion daily for five consecutive days every 21 days. Thirty-one patients were enrolled at 8 dose levels. Most common nonhematologic side effects were diarrhea (29%), vomiting (19%), nausea (19%), lethargy (13%), and abdominal pain (10%). The main hematologic toxicity was prolonged neutropenia. Nine patients had a best response of stable disease with a median duration of 2.7 months (range: 2.3–20.6 months). The study was closed without reaching the maximum tolerated dose (MTD) due to excessive toxicity in a companion trial resulting in termination of development of this agent. Bay 38-3441 was well tolerated in this study with granulocytopenia as the main hematologic toxicity. This study showed that glycoconjugation is a feasible delivery technique for camptothecin.The study medication, Bay 43-9006 and a partial funding for the study were provided by Bayer Inc.     

Doing involvement: A qualitative study exploring the ‘work’ of involvement enacted by older people and their carers during transition from hospital to home

ContextBeing involved in one''s care is prioritised within UK healthcare policy to improve care quality and safety. However, research suggests that many older people struggle with this.DesignWe present focused ethnographic research exploring older peoples'' involvement in healthcare from hospital to home.ResultsWe propose that being involved in care is a dynamic form of labour, which we call ‘involvement work’ (IW). In hospital, many patients ‘entrust’ IW to others; indeed, when desired, maintaining control, or being actively involved, was challenging. Patient and professionals'' expectations, alongside hospital processes, promoted delegation; staff frequently did IW on patients'' behalf. Many people wanted to resume IW postdischarge, but struggled because they were out of practice.DiscussionPreference and capacity for involvement was dynamic, fluctuating over time, according to context and resource accessibility. The challenges of resuming IW were frequently underestimated by patients and care providers, increasing dependence on others post‐discharge and negatively affecting peoples'' sense and experience of (in)dependence.ConclusionsA balance needs to be struck between respecting peoples'' desire/capacity for non‐involvement in hospital while recognising that ‘delegating’ IW can be detrimental. Increasing involvement will require patient and staff roles to be reframed, though this must be done acknowledging the limits of patient desire, capability,and resources. Hospital work should be (re)organised to maximise involvement where possible and desired.Patient/Public ContributionOur Patient and Public Involvement and Engagement Panel contributed to research design, especially developing interview guides and patient‐facing documentation. Patients were key participants within the study; it is their experiences represented.     

Validation of a test meal paradigm to experimentally manipulate meal-related fears: A registered report

Fear is central to conceptualizations of weight and shape-focused eating disorders. The current study will examine the reliability and validity of a test meal paradigm that varies perceptions of fat content to manipulate fear. Undergraduate women with elevated eating pathology (N = 96) will be randomized to one of three test meal conditions: two “low” fat yogurts, two “high” fat yogurts, or one “high” fat and one “low” fat yogurt. In actuality, all yogurts will have the same fat content. Supporting reliability, we hypothesize that self-reported fear and electrodermal activity (psychophysiological index of fear-related arousal) will exhibit good test–retest reliability over a 48-hr period in the “high” fat/“high” fat and “low” fat/“low” fat conditions. Supporting construct validity, self-reported fear and electrodermal activity will be elevated during the “high” versus “low” fat condition and responses to the “high" fat condition will correlate with fear of food, eating, and weight gain. Supporting discriminant validity, self-reported disgust and anger will be comparable in the “high” and “low” fat conditions and will exhibit weak correlations with trait measures of disgust and anger. This experimental paradigm will allow researchers to manipulate fear in order understand the mechanisms by which fear maintains eating pathology.     

Diet Quality and Cognitive Performance in Australian Adults Aged 55–85 Years: A Cross-Sectional Analysis of the Hunter Community Study Cohort

There is a lack of evidence to determine if diet quality is associated with cognitive performance in older adults. Therefore, the aim of this study was to examine whether diet quality is associated with cognitive performance among older adults. A cross-sectional, secondary analysis of baseline data from the Hunter Community Study (HCS), comparing diet quality, measured using the Australian Recommended Food Score (ARFS), along with validated cognitive performance instruments the Audio Recorded Cognitive Screen (ARCS) and the Mini-Mental State Examination (MMSE) were undertaken in adults aged 55–85 years, living in Newcastle, NSW, Australia. Adjusted linear regression analyses showed that, compared with the lowest ARFS quintile, those in the highest quintile had an ARCS score 5.883 units greater (p < 0.001; R² = 0.0098). Furthermore, when quintiles of ARFS score were tested against each ARCS sub-scale score, statistically significant associations were observed with the greatest effect for the Memory (β = 4.055; p = 0.001; R² = 0.0065) and Attention (β = 4.136; p = 0.002; R² = 0.0047) domains. No statistically significant associations were observed between quintiles of ARFS and MMSE score in the adjusted linear regression analyses. In conclusion, a positive association was observed between diet quality and cognitive performance within this sample of older Australian adults. Further investigation of the above association over time, when follow-up data becomes available, in longitudinal analysis is recommended.     

Dissolution and Translational Modeling Strategies Enabling Patient-Centric Drug Product Development: the M-CERSI Workshop Summary Report

On May 15th–17th, 2017, the US FDA and the International Consortium for Innovation and Quality in Pharmaceutical Development (IQ) held a workshop at the University of Maryland’s Center of Excellence in Regulatory Science and Innovation (M-CERSI), to discuss the role of dissolution testing and translational modeling and simulation in enabling patient-centric solid oral drug product development. This 3-day event was attended by scientists from regulatory agencies, pharmaceutical companies, and academia. The workshop included podium presentations followed by breakout session discussions. The first day of the meeting focused on the challenges in dissolution method development and the role of dissolution testing throughout drug product development. On the second day, approaches to establish a link between in vitro testing and in vivo drug product performance (e.g., systemic exposure) were presented. Overall success rates and challenges in establishing IVIVCs via traditional and modern physiologically based pharmacokinetic (PBPK) modeling and simulation approaches were discussed. Day 3 provided an opportunity to discuss the expectations for establishing clinically relevant drug product specifications (CRDPS). It was recognized that understanding the impact of formulation and process variations on dissolution and in vivo performance is critical for most drug products formulated with poorly soluble drugs to ensure consistent product performance. The breakout sessions served as platforms for discussing controversial topics such as the clarification of dissolution terminology, PBPK model development and validation expectations, and approaches to set CRDPS. The meeting concluded with a commitment to continue the dialog between regulators, industry, and academia to advance overall product quality understanding.