Pharmacovigilance in hospice/palliative care: rapid report of net clinical effect of metoclopramide

Background: Understanding the performance of prescribed medications in day-to-day practice is important to minimize harm, maximize clinical benefits, and, eventually, better target the people who are most likely to benefit, especially in hospice/palliative care where there may be limited time to optimize prescribing. Metoclopramide, a benzamide prokinetic antiemetic, is widely used for a number of indications including nausea, vomiting, hiccups, and reflux. It has recently had a new ‘‘black box’’ warning issued by the Food and Drug Administration in relation to tardive dyskinesia to limit use to 12 weeks. Methods: A consecutive cohort of patients from 12 participating centers in two countries who were having metoclopramide initiated had data collected at three time points—baseline, 2 days (clinical benefit), and day 7 (clinical harm). Additionally, harms could be recorded at any time. Results: Of the 53 people included in the cohort, 23 (43%) reported benefit at 48 hours, but only 18 (34%) of these people were still using it one week after commencing it. For the other 5, the medication was ceased due to harms. The most frequent harms were akathisia (n = 4), headache (n = 4), and abdominal pain (n = 4). Nine people (17%) had no clinical benefit and experienced harms. Conclusion: Overall, one in three people gained net clinical benefit at one week. Limiting effects include sideeffects that need to be sought actively in clinical care

Vascular changes in diabetic retinopathy-a longitudinal study in the Nile rat

Diabetic retinopathy is the most common microvascular complication of diabetes and is a major cause of blindness, but an understanding of the pathogenesis of the disease has been hampered by a lack of accurate animal models. Here, we explore the dynamics of retinal cellular changes in the Nile rat (Arvicanthis niloticus), a carbohydrate-sensitive model for type 2 diabetes. The early retinal changes in diabetic Nile rats included increased acellular capillaries and loss of pericytes that correlated linearly with the duration of diabetes. These vascular changes occurred in the presence of microglial infiltration but in the absence of retinal ganglion cell loss. After a prolonged duration of diabetes, the Nile rat also exhibits a spectrum of retinal lesions commonly seen in the human condition including vascular leakage, capillary non-perfusion, and neovascularization. Our longitudinal study documents a range and progression of retinal lesions in the diabetic Nile rat remarkably similar to those observed in human diabetic retinopathy, and suggests that this model will be valuable in identifying new therapeutic strategies

Using haloperidol as an anti-emetic in palliative care: informing practice through evidence from cancer treatment and post-operative contexts

YesNausea and vomiting are common symptoms in palliative care. Haloperidol is often used as an antiemetic in this context, although direct evidence supporting this practice is limited. To evaluate the efficacy and clinical use of haloperidol as an antiemetic in nonpalliative care contexts to inform practice, the authors conducted a rapid review of (i) published evidence to supplement existing systematic reviews, and (ii) practical aspects affecting the use of haloperidol including formulations and doses that are commonly available internationally. In nausea and vomiting related to cancer treatment, haloperidol was superior to control in two small studies. In postoperative nausea and vomiting (PONV), two randomized controlledtrials found treatment with haloperidol comparable to ondansetron. In palliative care, an observational study found a complete response rate of 24% with haloperidol (one in four patients) which would be consistent with a number needed to treat (NNT) of 3 to 5 derived from PONV. There remains insufficient direct evidence to definitively support the use of haloperidol for the management of nausea and vomiting in palliative care. However, generalizing evidence from other clinical contexts may have some validity

Comparative patterns of plant invasions in the mediterranean biome

The objective of this work was to compare and contrast the patterns of alien plant invasions in the world’s five mediterranean-climate regions (MCRs). We expected landscape age and disturbance history to have bearing on levels of invasion. We assembled a database on naturalized alien plant taxa occurring in natural and semi-natural terrestrial habitats of all five regions (specifically Spain, Italy, Greece and Cyprus from the Mediterranean Basin, California, central Chile, the Cape Region of South Africa and Southwestern - SW Australia). We used multivariate (hierarchical clustering and NMDS ordination) trait and habitat analysis to compare characteristics of regions, taxa and habitats across the mediterranean biome. Our database included 1627 naturalized species with an overall low taxonomic similarity among the five MCRs. Herbaceous perennials were the most frequent taxa, with SW Australia exhibiting both the highest numbers of naturalized species and the highest taxonomic similarity (homogenization) among habitats, and the Mediterranean Basin the lowest. Low stress and highly disturbed habitats had the highest frequency of invasion and homogenization in all regions, and high natural stress habitats the lowest, while taxonomic similarity was higher among different habitats in each region than among regions. Our analysis is the first to describe patterns of species characteristics and habitat vulnerability for a single biome. We have shown that a broad niche (i.e. more than one habitat) is typical of naturalized plant species, regardless of their geographical area of origin, leading to potential for high homogenization within each region. Habitats of the Mediterranean Basin are apparently the most resistant to plant invasion, possibly because their landscapes are generally of relatively recent origin, but with a more gradual exposure to human intervention over a longer period

No evidence for the association of DRD4 with ADHD in a Taiwanese population within-family study

BACKGROUND: Attention Deficit Hyperactivity Disorder (ADHD) is a prevalent and highly heritable childhood disorder. The dopamine D4 receptor (DRD4) gene has shown a genetic association with ADHD in Caucasian populations with meta-analysis indicating a small but significant effect across datasets. It remains uncertain whether this association can be generalised to non-Caucasian ethnic groups. Here we investigate two markers within the DRD4 gene in a Taiwanese population, the exon 3 variable number tandem repeat (VNTR) and a 5' 120 base-pair duplication. METHODS: Within-family transmission disequilibrium tests of association of the 5' 120 base-pair duplication, and exon 3 VNTR in a Taiwanese population. RESULTS: No evidence of association of ADHD with either polymorphism in this population was observed. CONCLUSION: The DRD4 gene markers investigated were not found to be associated with ADHD in this Taiwanese sample. Further work in Taiwanese and other Asian populations will therefore be required to establish whether the reports of association of DRD4 genetic variants in Caucasian samples can be generalised to Asian populations

Acute ischemic heart disease and interventional cardiology: a time for pause

BACKGROUND: A major change has occurred in the last few years in the therapeutic approach to patients presenting with all forms of acute coronary syndromes. Whether or not these patients present initially to tertiary cardiac care centers, they are now routinely referred for early coronary angiography and increasingly undergo percutaneous revascularization. This practice is driven primarily by the angiographic image and technical feasibility. Concomitantly, there has been a decline in expectant or ischemia-guided medical management based on specific clinical presentation, response to initial treatment, and results of noninvasive stratification. This 'tertiarization' of acute coronary care has been fuelled by the increasing sophistication of the cardiac armamentarium, the peer-reviewed publication of clinical studies purporting to show the superiority of invasive cardiac interventions, and predominantly supporting (non-peer-reviewed) editorials, newsletters, and opinion pieces. DISCUSSION: This review presents another perspective, based on a critical reexamination of the evidence. The topics addressed are: reperfusion treatment of ST-elevation myocardial infarction; the indications for invasive intervention following thrombolysis; the role of invasive management in non-ST-elevation myocardial infarction and unstable angina; and cost-effectiveness and real world considerations. A few cases encountered in recent practice in community and tertiary hospitals are presented for illustrative purposes The numerous and far-reaching scientific, economic, and philosophical implications that are a consequence of this marked change in clinical practice as well as healthcare, decisional and conflict of interest issues are explored. SUMMARY: The weight of evidence does not support the contemporary unfocused broad use of invasive interventional procedures across the spectrum of acute coronary clinical presentations. Excessive and unselective recourse to these procedures has deleterious implications for the organization of cardiac health care and undesirable economic, scientific and intellectual consequences. It is suggested that there is need for a new equilibrium based on more refined clinical risk stratification in the treatment of patients who present with acute coronary syndromes

Relative survival and excess mortality following primary percutaneous coronary intervention for ST-elevation myocardial infarction

Background: High survival rates are commonly reported following primary percutaneous coronary intervention for ST-elevation myocardial infarction, with most contemporary studies reporting overall survival. Aims: The aim of this study was to describe survival following primary percutaneous coronary intervention for ST-elevation myocardial infarction corrected for non-cardiovascular deaths by reporting relative survival and investigate clinically significant factors associated with poor long-term outcomes. Methods and Results: Using the prospective UK Percutaneous Coronary Intervention registry, primary percutaneous coronary intervention cases (n=88,188; 2005–2013) were matched to mortality data for the UK populace. Crude five-year relative survival was 87.1% for the patients undergoing primary percutaneous coronary intervention and 94.7% for patients 75 years: 4.69, 4.27–5.16). After four years, there was no excess mortality for ages 56–65 years (excess mortality rate ratio 1.27, 0.95–1.70), but persisting excess mortality for older groups (66–75 years: excess mortality rate ratio 1.72, 1.30–2.27; >75 years: 1.66, 1.15–2.41). Excess mortality was associated with cardiogenic shock (excess mortality rate ratio 6.10, 5.72–6.50), renal failure (2.52, 2.27–2.81), left main stem stenosis (1.67, 1.54–1.81), diabetes (1.58, 1.47–1.69), previous myocardial infarction (1.52, 1.40–1.65) and female sex (1.33, 1.26–1.41); whereas stent deployment (0.46, 0.42–0.50) especially drug eluting stents (0.27, 0.45–0.55), radial access (0.70, 0.63–0.71) and previous percutaneous coronary intervention (0.67, 0.60–0.75) were protective. Conclusions: Following primary percutaneous coronary intervention for ST-elevation myocardial infarction, long-term cardiovascular survival is excellent. Failure to account for non-cardiovascular death may result in an underestimation of the efficacy of primary percutaneous coronary intervention

Influence of Psychological Factors on Pain and Disability in Anterior Knee Pain Patients

AKP patients express chronic pain but also disability. However, the correlation between pain and disability is not complete and linear. Some patients with a lot of pain show mild disability while others with much less pain also show great disability. The disability is profoundly influenced by other emotional and cognitive factors that are associated with the perception of pain. Therefore, the clinical efforts do not have to be focused only on treating the pain as a feeling but on identifying and modifying these factor

Comparative Genomics of the Apicomplexan Parasites Toxoplasma gondii and Neospora caninum: Coccidia Differing in Host Range and Transmission Strategy

Toxoplasma gondii is a zoonotic protozoan parasite which infects nearly one third of the human population and is found in an extraordinary range of vertebrate hosts. Its epidemiology depends heavily on horizontal transmission, especially between rodents and its definitive host, the cat. Neospora caninum is a recently discovered close relative of Toxoplasma, whose definitive host is the dog. Both species are tissue-dwelling Coccidia and members of the phylum Apicomplexa; they share many common features, but Neospora neither infects humans nor shares the same wide host range as Toxoplasma, rather it shows a striking preference for highly efficient vertical transmission in cattle. These species therefore provide a remarkable opportunity to investigate mechanisms of host restriction, transmission strategies, virulence and zoonotic potential. We sequenced the genome of N. caninum and transcriptomes of the invasive stage of both species, undertaking an extensive comparative genomics and transcriptomics analysis. We estimate that these organisms diverged from their common ancestor around 28 million years ago and find that both genomes and gene expression are remarkably conserved. However, in N. caninum we identified an unexpected expansion of surface antigen gene families and the divergence of secreted virulence factors, including rhoptry kinases. Specifically we show that the rhoptry kinase ROP18 is pseudogenised in N. caninum and that, as a possible consequence, Neospora is unable to phosphorylate host immunity-related GTPases, as Toxoplasma does. This defense strategy is thought to be key to virulence in Toxoplasma. We conclude that the ecological niches occupied by these species are influenced by a relatively small number of gene products which operate at the host-parasite interface and that the dominance of vertical transmission in N. caninum may be associated with the evolution of reduced virulence in this species