Influence of individual, illness and environmental factors on place of death among people with neurodegenerative diseases: a retrospective, observational, comparative cohort study.

BACKGROUND: In long-term neurological conditions, location of death is poorly understood but is seen as a marker of quality of dying. OBJECTIVE: To examine individual, illness and environmental factors on place of death among people with multiple sclerosis (MS) and Parkinson's disease (PD) in isolation or in combination and compare them with people without either condition. METHODS: Retrospective, observational, comparative cohort study of 582 people with MS, 579 people with PD and 95 controls from UK Multiple Sclerosis and Parkinson's Disease Tissue Bank. A subset of people with MS and PD were selected for analysis of individual clinical encounters 2 years before death and further subset of all groups for analysis of impact of advance care planning (ACP) and recognition of dying. RESULTS: People with MS died more often (50.8%) in hospital than those with PD (35.3%). Examining individual clinical encounters over 2 years (4931 encounters) identified increased contact with services 12 months before death (F(1, 58)=69.71, p<0.0001) but was not associated with non-hospital deaths (F(1, 58)=1.001, p=0.321). The presence of ACPs and recognition of dying were high among people with MS and PD and both associated with a non-hospital death. ACPs were more likely to prevent hospital deaths when initiated by general practitioners (GPs) compared with other professional groups (χ2=68.77, p=0.0007). CONCLUSIONS: For people with MS and PD, ACPs contribute to reducing dying in hospital. ACPs appear to be most effective when facilitated by GPs underlining the importance of primary care involvement in delivering holistic care at the end of life.

Getting It Straight: Accommodating Rectilinear Behavior in Captive Snakes-A Review of Recommendations and Their Evidence Base.

Snakes are sentient animals and should be subject to the accepted general welfare principles of other species. However, they are also the only vertebrates commonly housed in conditions that prevent them from adopting rectilinear behavior (ability to fully stretch out). To assess the evidence bases for historical and current guidance on snake spatial considerations, we conducted a literature search and review regarding recommendations consistent with or specifying ≥1 × and <1 × snake length enclosure size. We identified 65 publications referring to snake enclosure sizes, which were separated into three categories: peer-reviewed literature (article or chapter appearing in a peer-reviewed journal or book, n = 31), grey literature (government or other report or scientific letter, n = 18), and opaque literature (non-scientifically indexed reports, care sheets, articles, husbandry books, website or other information for which originating source is not based on scientific evidence or where scientific evidence was not provided, n = 16). We found that recommendations suggesting enclosure sizes shorter than the snakes were based entirely on decades-old 'rule of thumb' practices that were unsupported by scientific evidence. In contrast, recommendations suggesting enclosure sizes that allowed snakes to fully stretch utilized scientific evidence and considerations of animal welfare. Providing snakes with enclosures that enable them to fully stretch does not suggest that so doing allows adequate space for all necessary normal and important considerations. However, such enclosures are vital to allow for a limited number of essential welfare-associated behaviors, of which rectilinear posturing is one, making them absolute minimum facilities even for short-term housing.

Investigations into the concept of a threshold for topoisomerase inhibitor-induced clastogenicity.

Although the application of the concept of a threshold to risk assessment is widespread, there remains little experimental evidence for the existence of thresholds for genotoxic compounds, other than aneugens. The clastogenicity of topoisomerase inhibitors is believed to result from the transient stabilization of the topoisomerase enzyme with DNA during the catalytic cycle. This leads to the formation of a stabilized cleavage complex, which, in turn, may result in the formation of a DNA strand break. This indirect mechanism of clastogenicity is the basis for the concept of threshold for this class of drug. Using micronucleus induction in L5178Y mouse lymphoma cells as a genotoxic end-point, a three pronged approach was used to examine whether the concept of a threshold for clastogenicity could be demonstrated for topoisomerase type II inhibitors in vitro. This involved (i) the study of mechanism (TARDIS assay), (ii) hypothesis testing versus estimation (i.e. scoring up to 10,000 cells/treatment at concentrations immediately above and below the NOEL for micronucleus induction) and (iii) statistical modelling of the concentration-response curves for micronucleus induction. Several topoisomerase type II inhibitors were investigated with varying clastogenic potencies (etoposide = doxorubicin < genistein < ciprofloxacin). Pragmatic thresholds for clastogenicity in L5178Y cells were defined at 0.00236 microg/ml for etoposide, 0.00151 microg/ml for doxorubicin, 1 microg/ml for genistein and 50 microg/ml for ciprofloxacin. In addition, it was demonstrated that etoposide-induced clastogenicity was concentration and time dependent. These results, along with mechanistic data showing that all of the compounds induced concentration-dependent increases in the formation of topoisomerase II stabilized cleavage complexes, provide a weight of evidence to support a threshold concept for clastogenicity with topoisomerase II poisons.