Analgesic prescribing in care home residents: how epidemiological studies may inform clinical practice

Care home residents are often frail with multiple comorbidities and cognitive impairment, most commonly caused by dementia. This population is under-represented in clinical trials, leading to a lack of valid and reliable evidence to inform clinicians’ prescribing practice. This paper summarizes how epidemiological research conducted in similar populations can inform pain management by describing pain prevalence, risk factors, typical features and functional consequences. This evidence can help overcome the numerous barriers to optimal pain management in care home residents

High resolution radio study of the Pulsar Wind Nebula within the Supernova Remnant G0.9+0.1

We have conducted a radio study at 3.6, 6 and 20 cm using ATCA and VLA and reprocessed XMM-Newton and Chandra data of the pulsar wind nebula (PWN) in the supernova remnant (SNR) G0.9+0.1. The new observations revealed that the morphology and symmetry suggested by Chandra observations (torus and jet-like features) are basically preserved in the radio range in spite of the rich structure observed in the radio emission of this PWN, including several arcs, bright knots, extensions and filaments. The reprocessed X-ray images show for the first time that the X-ray plasma fills almost the same volume as the radio PWN. Notably the X-ray maximum does not coincide with the radio maximum and the neutron star candidate CXOU J174722.8-280915 lies within a small depression in the radio emission. From the new radio data we have refined the flux density estimates, obtaining S(PWN) ~ 1.57 Jy, almost constant between 3.6 and 20 cm. For the whole SNR (compact core and shell), a flux density S(at 20 cm)= 11.5 Jy was estimated. Based on the new and the existing 90 cm flux density estimates, we derived alpha(PWN)=-0.18+/-0.04 and alpha(shell)=-0.68+/- 0.07. From the combination of the radio data with X-ray data, a spectral break is found near nu ~ 2.4 x 10^(12) Hz. The total radio PWN luminosity is L(radio)=1.2 x 10^(35) erg s^(-1) when a distance of 8.5 kpc is adopted. By assuming equipartition between particle and magnetic energies, we estimate a nebular magnetic field B = 56 muG. The associated particle energy turns out to be U(part)=5 x 10^(47) erg and the magnetic energy U(mag)=2 x 10^(47) erg. Based on an empirical relation between X-ray luminosity and pulsar energy loss rate, and the comparison with the calculated total energy, a lower limit of 1100 yr is derived for the age of this PWN.Comment: 10 pages,8 figures, accepted for publication in A&A, June 13 200

Physicochemical characterisation of disease associated abnormal prion proteins

The central feature of prion disease is the conversion of normal host-encoded cellular prion protein, PrPc, to an abnormal isoform, PrP. PrP80 appears to be the principal, if not the sole, component of infectious prions. Prion strain diversity seems to be encoded within PrP itself through a combination of PrP conformation, glycosylation and possibly other, as yet, unidentified post-translational modifications. Efficient purification of PrP will facilitate detailed chemical characterisation and investigation of conformations or assembly states required for prion infectivity. Purification of denatured PrP has been achieved through enrichment from brain homogenate using selective precipitation followed by chemical and thermal denaturation and isolation by immunoafTinity chromatography. These methods have isolated PrP from rodent prion strains with a yield of 50 % and purity of > 90 % of total protein and for the first time permit isolation of full length denatured PrPSc facilitating comprehensive structural analysis. Purified denatured PrP is expected to have all the covalent post-translational modifications that may be required for prion infectivity. In attempts to reconstitute prion infectivity, denatured PrP was refolded under different solvent conditions and assessed for changes in solubility, resistance to proteolytic digestion and infectivity in bioassay. Although distinct changes in the physicochemical properties of PrP were observed, to-date no evidence for reconstitution of prion infectivity has been found. In the course of these studies, it was discovered that Cu2f ions inhibit proteinase K activity and a detailed kinetic description of this inhibition was obtained. The lack of prion infectivity seen in refolded preparations of denatured PrP suggests a requirement for other as yet unidentified co-factors. The identity of PrP interacting proteins was investigated during the purification of PrP under differential extraction conditions in which prion infectivity was observed using an in vitro assay. Proteinase K digestion gave a change in prion infectivity implying that a correlation with the removal of a protease sensitive component occurred. Continuation of these studies may facilitate the identification of co-factors required for specific prion infectivity

Modelling Nonlinear Sequence Generators in terms of Linear Cellular Automata

In this work, a wide family of LFSR-based sequence generators, the so-called Clock-Controlled Shrinking Generators (CCSGs), has been analyzed and identified with a subset of linear Cellular Automata (CA). In fact, a pair of linear models describing the behavior of the CCSGs can be derived. The algorithm that converts a given CCSG into a CA-based linear model is very simple and can be applied to CCSGs in a range of practical interest. The linearity of these cellular models can be advantageously used in two different ways: (a) for the analysis and/or cryptanalysis of the CCSGs and (b) for the reconstruction of the output sequence obtained from this kind of generators.Comment: 15 pages, 0 figure

Temporal Trends in Analgesic Use in Long-Term Care Facilities: A Systematic Review of International Prescribing.

OBJECTIVES: To explore global changes in the prescription of analgesic drugs over time in the international long-term care (LTC) population. DESIGN: Systematic review. SETTING: We included original research articles in English, published and unpublished, that included number of participants, country and year(s) of data collection, and prescription of analgesics (analgesics not otherwise specified, opioids, acetaminophen; scheduled only, or scheduled plus as needed (PRN)). PARTICIPANTS: LTC residents. MEASUREMENTS: We searched PubMed, EMBASE, CINAHL, International Pharmaceutical Abstracts, PsycINFO, Cochrane, Web of Science, Google Scholar, using keywords for LTC facilities and analgesic medication; hand-searched references of eligible papers; correspondence. Studies were quality rated using an adapted Newcastle-Ottawa scale. Pearson correlation coefficients were generated between percentage of residents prescribed an analgesic and year of data collection. If available, we investigated changes in acetaminophen and opioid prescriptions. RESULTS: Forty studies met inclusion criteria. A moderate correlation (0.59) suggested that scheduled prescription rates for analgesics have increased over time. Similar findings were reflected in scheduled prescriptions for acetaminophen and opioids. No increase was seen when analyzing scheduled plus PRN analgesics. Use of opioids (scheduled plus PRN) appears to have increased over time. CONCLUSION: Worldwide, use of opioids and acetaminophen has increased in LTC residents. Research is needed to explore whether this reflects appropriate pain management for LTC residents and if PRN medication is used effectively

Ketamine for depression

Over the last two decades, the dissociative anaesthetic agent ketamine, an uncompetitive N-Methyl-D-Aspartate (NMDA) receptor antagonist, has emerged as a novel therapy for treatment-resistant depression (TRD), demonstrating rapid and robust antidepressant effects within hours of administration. Ketamine is a racemic mixture composed of equal amounts of (S)-ketamine and (R)-ketamine. Although ketamine currently remains an off-label treatment for TRD, an (S)-ketamine nasal spray has been approved for use in TRD (in conjunction with an oral antidepressant) in the United States and Europe. Despite the promise of ketamine, key challenges including how to maintain response, concerns regarding short and long-term side-effects and the potential for abuse remain. This review provides an overview of the history of ketamine, its use in psychiatry and its basic pharmacology. The clinical evidence for the use of ketamine in depression and potential adverse effects associated with treatment are summarized. A synopsis of some of the putative neurobiological mechanisms underlying ketamine’s rapid-acting antidepressant effects is provided before finally outlining future research directions, including the need to identify biomarkers for predicting response and treatment targets that may be used in the development of next-generation rapid-acting antidepressants that may lack ketamine’s side-effects or abuse potential

Psychotropic prescribing for English care home residents with dementia compared with national guidance: findings from the MARQUE national longitudinal study

Background Despite policy pressure and concerns regarding the use of antipsychotics and benzodiazepines, many care home residents with dementia are prescribed psychotropic medication, often off licence. This is the first large study to report psychotropic prescribing and ‘as required’ administration patterns in English care homes. Aims To explore the prevalence and associates of psychotropic prescription in care home residents with dementia and compare the results with national guidance. Method We collected data in a longitudinal cohort study of residents with diagnosed or probable dementia in 86 care homes in England in 2014–2016. We reported the prevalence of psychotropic (antipsychotics, anxiolytics/hypnotics, antidepressants) prescriptions and drug receipt. We explored the associations between resident factors (sociodemographic, agitation [Cohen–Mansfield Agitation Inventory], dementia severity [Clinical Dementia Rating]) and care home factors (type, ownership, size, dementia registration/specialism, quality rating) in prescription and ‘as required’ administration, using multilevel regression models. Results We analysed data from 1425 residents. At baseline, 822 residents (57.7%, 95% CI: 55.1–60.2) were prescribed a psychotropic drug, 310 residents (21.8% 95% CI: 19.7–24.0) were prescribed an anxiolytic/hypnotic, 232 (94.3%, 95% CI: 90.6–96.6) were prescribed one antipsychotic and 14 (5.7%, 95% CI: 3.4–9.4) were prescribed two antipsychotics. The median prescription duration during the study was 1 year. Residents with clinically significant agitation were prescribed more antipsychotics (odds ratio [OR] = 2.00, 95% CI: 1.64–2.45) and anxiolytics/hypnotics (OR = 2.81, 95% CI: 2.31–3.40). Conclusions Antipsychotics and anxiolytics/hypnotics are more commonly prescribed for people with dementia in care homes than in the community, and prescribing may not reflect guidelines. Policies which advocate reduced use of psychotropics should better support psychosocial interventions

Three-dimensional imaging of progressive facial hemiatrophy (Parry-Romberg syndrome) with unusual conjunctival findings

Progressive hemifacial atrophy, also known as Parry-Romberg syndrome, is an uncommon degenerative condition which is poorly defined. It is characterized by a slow and progressive atrophy affecting one side of the face. The onset usually occurs during the first two decades of life. Characteristically, the atrophy progresses slowly for several years, and then it becomes stable. Ophthalmic involvement is common, with progressive enophthalmos which is a frequent finding. Cutaneous pigmentation is common in such conditions, however its extension to the conjunctiva is rarely reported. We report a case of Parry Romberg syndrome with characteristic clinical and radiographic presentation accompanied with rare ocular findings. The clinical features, radiological findings, and differential diagnoses to be considered, and the available treatment options are discussed in this report

Factors influencing prescription and administration of analgesic medication: A longitudinal study of people with dementia living in care homes

Objectives: To (1) describe the prescription and administration of regular and ‘as required’ (pro re nata [PRN]) analgesics in English care homes, (2) investigate individual and care home factors associated with analgesic use. Methods: We collected data (2014–2016) at 0‐, 4‐, and 12‐months nested in a longitudinal cohort study of 86 English care homes about residents with diagnosed or probable dementia. We describe analgesics prescribed as regular or PRN medication, by class, and PRN administration. We explored individual differences (sociodemographic; dementia severity [Clinical Dementia Rating]), and care home differences (type; ownership; number of beds; dementia‐registered/specialist; Care Quality Commission rating) in prescription and administration using multilevel regression models. Results: Data were available for 1483 residents. At baseline, 967 residents (67.9%) were prescribed analgesics: 426 residents (28.7%) prescribed regular analgesics and 670 (45.2%) prescribed PRN. Paracetamol was the most prescribed analgesic (56.7%), with PRN prescriptions more common than regular (39.7% vs. 16.6%). Across all study visits, 344 residents (mean = 41.9%) with a PRN prescription did not receive any analgesic in the 2 weeks prior to data collection. Male residents and those with severe dementia received fewer analgesics. Care homes differences in PRN administration were not explained by the modelled variables. Conclusions: Pain management in English care homes largely relies on PRN paracetamol that is frequently prescribed but infrequently administered. Care homes differ in how often they administer PRN analgesics. Some care home residents particularly those with more severe dementia are likely to have untreated pain

Improved model identification for non-linear systems using a random subsampling and multifold modelling (RSMM) approach

In non-linear system identification, the available observed data are conventionally partitioned into two parts: the training data that are used for model identification and the test data that are used for model performance testing. This sort of 'hold-out' or 'split-sample' data partitioning method is convenient and the associated model identification procedure is in general easy to implement. The resultant model obtained from such a once-partitioned single training dataset, however, may occasionally lack robustness and generalisation to represent future unseen data, because the performance of the identified model may be highly dependent on how the data partition is made. To overcome the drawback of the hold-out data partitioning method, this study presents a new random subsampling and multifold modelling (RSMM) approach to produce less biased or preferably unbiased models. The basic idea and the associated procedure are as follows. First, generate K training datasets (and also K validation datasets), using a K-fold random subsampling method. Secondly, detect significant model terms and identify a common model structure that fits all the K datasets using a new proposed common model selection approach, called the multiple orthogonal search algorithm. Finally, estimate and refine the model parameters for the identified common-structured model using a multifold parameter estimation method. The proposed method can produce robust models with better generalisation performance