Pharmacovigilance in hospice/palliative care: net effect of haloperidol for nausea or vomiting

Background: Haloperidol is widely prescribed as an antiemetic in patients receiving palliative care, but there is limited evidence to support and refine its use. Objective: To explore the immediate and short-term net clinical effects of haloperidol when treating nausea and/or vomiting in palliative care patients. Design: A prospective, multicenter, consecutive case series. Setting/Subjects: Twenty-two sites, five countries: consultative, ambulatory, and inpatient services. Measurements: When haloperidol was started in routine care as an antiemetic, data were collected at three time points: baseline; 48 hours (benefits); day seven (harms). Clinical effects were assessed using the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI CTCAE). Results: Data were collected (May 2014–March 2016) from 150 patients: 61% male; 86% with cancer; mean age 72 (standard deviation 11) years and median Australian-modified Karnofsky Performance Scale 50 (range 10–90). At baseline, nausea was moderate (88; 62%) or severe (11; 8%); 145 patients reported vomiting, with a baseline NCI CTCAE vomiting score of 1.0. The median (range) dose of haloperidol was 1.5 mg/24 hours (0.5–5 mg/24 hours) given orally or parenterally. Five patients (3%) died before further data collection. At 48 hours, 114 patients (79%) had complete resolution of their nausea and vomiting, with greater benefit seen in the resolution of nausea than vomiting. At day seven, 37 (26%) patients had a total of 62 mild/moderate harms including constipation 25 (40%); dry mouth 13 (21%); and somnolence 12 (19%). Conclusions: Haloperidol as an antiemetic provided rapid net clinical benefit with low-grade, short-term harms

\u3csup\u3e1\u3c/sup\u3eH-MRS Metabolites in Adults with Down Syndrome: Effects of Dementia

To determine if proton magnetic resonance spectroscopy (1H-MRS) detect differences in dementia status in adults with Down syndrome (DS), we used 1H-MRS to measure neuronal and glial metabolites in the posterior cingulate cortex in 22 adults with DS and in 15 age- and gender-matched healthy controls. We evaluated associations between 1H-MRS results and cognition among DS participants. Neuronal biomarkers, including N-acetylaspartate (NAA) and glutamate-glutamine complex (Glx), were significantly lower in DS patients with Alzheimer\u27s should probably be changed to Alzheimer (without \u27 or s) through ms as per the new naming standard disease (DSAD) when compared to non-demented DS (DS) and healthy controls (CTL). Neuronal biomarkers therefore appear to reflect dementia status in DS. In contrast, all DS participants had significantly higher myo-inositol (MI), a putative glial biomarker, compared to CTL. Our data indicate that there may be an overall higher glial inflammatory component in DS compared to CTL prior to and possibly independent of developing dementia. When computing the NAA to MI ratio, we found that presence or absence of dementia could be distinguished in DS. NAA, Glx, and NAA/MI in all DS participants were correlated with scores from the Brief Praxis Test and the Severe Impairment Battery. 1H-MRS may be a useful diagnostic tool in future longitudinal studies to measure AD progression in persons with DS. In particular, NAA and the NAA/MI ratio is sensitive to the functional status of adults with DS, including prior to dementia

Practical dyspnea assessment: relationship between the 0–10 numerical rating scale and the four-level categorical verbal descriptor scale of dyspnea intensity

Context—Measurement of dyspnea is important for clinical care and research. Objectives—To characterize the relationship between the 0–10 Numerical Rating Scale (NRS) and four-level categorical Verbal Descriptor Scale (VDS) for dyspnea assessment. Methods—This was a substudy of a double-blind randomized controlled trial comparing palliative oxygen to room air for relief of refractory breathlessness in patients with life-limiting illness. Dyspnea was assessed with both a 0–10 NRS and a four-level categorical VDS over the one-week trial. NRS and VDS responses were analyzed in cross section and longitudinally. Relationships between NRS and VDS responses were portrayed using descriptive statistics and visual representations. Results—Two hundred twenty-six participants contributed responses. At baseline, mild and moderate levels of breathlessness were reported by 41.9% and 44.6% of participants, respectively. NRS scores demonstrated increasing mean and median levels for increasing VDS intensity, from a mean (SD) of 0.6 (±1.04) for VDS none category to 8.2 (1.4) for VDS severe category. The Spearman correlation coefficient was strong at 0.78 (P < 0.0001). Based on the distribution of NRS scores within VDS categories, we calculated test characteristics of two different cutpoint models. Both models yielded 75% correct translations from NRS to VDS; however, Model A was more sensitive for moderate or greater dyspnea, with fewer misses downcoded. Conclusion—There is strong correlation between VDS and NRS measures for dyspnea. Proposed practical cutpoints for the relationship between the dyspnea VDS and NRS are 0 for none, 1–4 for mild, 5–8 for moderate, and 9–10 for severe

Utilisation of the static Evans method to measure magnetic susceptibilities of transition metal acetylacetonate complexes as part of an undergraduate inorganic laboratory class

The Evans method is routinely utilised to collect paramagnetic susceptibility data via the employment of relevant Nuclear Magnetic Resonance (NMR) methods. As the sample is normally spun, the lack of such a function on benchtop NMR instrumentation required a “static” approach to be employed. We have utilised the static Evan’s method approach to measure the magnetic susceptibilities, and subsequently the effective magnetic moment, of a series of synthesised transition metal acetylacetonate complexes in order to appraise the d-electron configuration. The obtained values were compared to those obtained using a Guoy balance and theoretical calculations. The collection of T1 relaxation data further exemplifies the effect of the paramagnetic centre in terms of aiding relaxation, and therefore links to Magnetic Resonance Imaging (MRI) contrast agents, thus providing students with real-world perspective of the experiment conducted

Australia-modified Karnofsky Performance Scale and physical activity in COPD and lung cancer: an exploratory pooled data analysis

Objectives: Patient-relevant measures of functional status are required in chronic obstructive pulmonary disease (COPD) and lung cancer in clinical practice and research. We explored the relationship between the Australia-modified Karnofsky Performance Scale (AKPS) and measures of functional capacity and physical activity in these patient groups. Methods: Pooled clinical trial data were analysed to explore the relationship between AKPS and average daily steps (ADS), 6 min walk distance (6MWD), and body mass index, airflow obstruction, dyspnoea and exercise score (COPD group). Receiver operator characteristic curves were produced to compare sensitivity and specificity of cut-offs (no dependency >70, high dependency 70, the optimal ADS cut-points were COPD, 3342 steps (AUC 0.88, 95% CI 0.79 to 0.97, sensitivity 82%, specificity 76%), and lung cancer, 3380 steps (AUC 0.72, 95% CI 0.64 to 0.81, sensitivity 61%, specificity 74%), and for 6MWD (COPD only) 242 m (AUC 0.72, 95% CI 0.63 to 0.81, sensitivity 73%, specificity 34%). Conclusions: An AKPS score is strongly related to ADS in people with COPD and lung cancer. The AKPS may be useful in clinical practice and research to indicate levels of physical activity where ADS and 6 min walk test are not possible. Longitudinal data are needed to confirm these findings

A systematic review of strategies used to increase recruitment of people with cancer or organ failure into clinical trials: implications for palliative care research

Context. The challenges of palliative care clinical trial recruitment are well documented. Objectives. The aim of the study was to review tested strategies to improve recruitment to trials of people with a range of conditions who may access palliative care services but are not explicitly stated to be ‘‘palliative.’’ Methods. This was a systematic review with narrative description. The Cochrane, Embase, PubMed, PsycINFO, and CINAHL electronic databases were searched (English; January 2002 to February 2014) for quasi-experimental and randomized controlled trials (RCTs) testing the effect of recruitment strategies on accrual to clinical trials of people with organ failure and cancer. Titles, abstracts, and retrieved articles were screened by two researchers and categorized by recruitment challenge: 1) patients with reduced cognition, 2) those requiring emergency treatment, and 3) willingness of patients and clinical staff to contribute to trials. Results. Of 549 articles identified, 15 were included. Thirteen reported RCTs and two papers reported three quasiexperimental studies. Five were cluster RCTs of recruiting sites/institutions. One was a randomized cluster, crossover, feasibility study. Seven studies recruited patients with cancer. Others included patients with dementia, stroke, cardiovascular disease, diabetes, frail elderly, and bereaved carers. Some interventions improved recruitment: memory aid, contact before arrival, cluster consent, ‘‘opt out’’ consent. Others either reduced recruitment (formal mental capacity assessment) or made no difference (advance research directive; a variety of educational, supportive, and advertising interventions). Conclusion. Successful strategies from other disciplines could be considered by palliative care researchers. Tailored, efficient, evidence-based strategies must be developed, acknowledging that strategies with face validity are not necessarily the most effective

Pharmacovigilance in hospice/palliative care: the net immediate and short-term effects of dexamethasone for anorexia

Objectives Loss of appetite is prevalent in palliative care and distressing for patients and families. Therapies include corticosteroids or progestogens. This study explores the net effect of dexamethasone on anorexia. Methods Prospective data were collected when dexamethasone was started for anorexia as part of routine care. The National Cancer Institute’s Common Toxicity Criteria for Adverse Events (NCICTCAE) Likert scales assessed severity of anorexia and immediate and short-term harms at 2 time points: baseline and 7 days. Results This study (41 sites, 8 countries) collected data (July 2013 to July 2014) from 114 patients (mean age 71 (SD 11), 96% with cancer). Median Australian-modified Karnofsky Performance Scale was 50% (range 20–70). Mean baseline NCICTCAE anorexia score was 2.7 (SD 0.6; median 3). 6 patients died by day 7. Of 108 evaluable patients, 74 (68.5%; 95% CI 59.0% to 76.7%) reported ≥1 reduction anorexia scores by day 7, of whom 30 were 0. Mean dexamethasone dose on day 7 was 4.1 mg/day (SD 3.4; median 4; range 0–46 mg). 24 patients reported ≥1 harms (32.4% CI 22.6% to 44.1%; insomnia n=10, depression n=7, euphoria n=7 and hyperglycaemia n=7). Of 24 patients with no benefit, 10 reported ≥1 harms. Conclusions This study shows positive and negative effects of 7 days of dexamethasone as an appetite stimulant in patients with advanced life-limiting illnesses. Identifying clinicodemographic characteristics of people most at risk of harms with no benefit is a crucial next step. Longer term follow-up will help to understand longer term and cumulative harms

Persistent Amyloidosis following Suppression of Aβ Production in a Transgenic Model of Alzheimer Disease

BACKGROUND: The proteases (secretases) that cleave amyloid-β (Aβ) peptide from the amyloid precursor protein (APP) have been the focus of considerable investigation in the development of treatments for Alzheimer disease. The prediction has been that reducing Aβ production in the brain, even after the onset of clinical symptoms and the development of associated pathology, will facilitate the repair of damaged tissue and removal of amyloid lesions. However, no long-term studies using animal models of amyloid pathology have yet been performed to test this hypothesis. METHODS AND FINDINGS: We have generated a transgenic mouse model that genetically mimics the arrest of Aβ production expected from treatment with secretase inhibitors. These mice overexpress mutant APP from a vector that can be regulated by doxycycline. Under normal conditions, high-level expression of APP quickly induces fulminant amyloid pathology. We show that doxycycline administration inhibits transgenic APP expression by greater than 95% and reduces Aβ production to levels found in nontransgenic mice. Suppression of transgenic Aβ synthesis in this model abruptly halts the progression of amyloid pathology. However, formation and disaggregation of amyloid deposits appear to be in disequilibrium as the plaques require far longer to disperse than to assemble. Mice in which APP synthesis was suppressed for as long as 6 mo after the formation of Aβ deposits retain a considerable amyloid load, with little sign of active clearance. CONCLUSION: This study demonstrates that amyloid lesions in transgenic mice are highly stable structures in vivo that are slow to disaggregate. Our findings suggest that arresting Aβ production in patients with Alzheimer disease should halt the progression of pathology, but that early treatment may be imperative, as it appears that amyloid deposits, once formed, will require additional intervention to clear