The cost-effectiveness of high dose chemotherapy in the treatment of relapsed Hodgkin's disease and non-Hodgkin's lymphoma

As part of an NHS Executive Trent regional initiative we considered the role and cost-effectiveness of high dose chemotherapy in the treatment of relapsed Hodgkin's disease and non-Hodgkin's lymphoma. The key trials and case series show an additional patient benefit of 0.8–1.1 life years over standard chemotherapy. We estimate incremental cost per life year gained of £12 800–£17 600, which reduces further if long-term benefits are considered. High dose chemotherapy in these conditions is both life-saving and cost-effective. © 2000 Cancer Research Campaig

Cholesterol and coronary heart disease: screening and treatment

Coronary heart disease (CHD) is a major cause of morbidity and mortality in the United Kingdom, accounting for just under one quarter of all deaths in 1995: 27% among men and 21% among women.1 Although many CHD deaths occur among elderly people, CHD accounts for 31% of male and 13% of female deaths within the 45–64 age group

A role for TSPO in mitochondrial Ca2+ homeostasis and redox stress signaling

The 18 kDa translocator protein TSPO localizes on the outer mitochondrial membrane (OMM). Systematically overexpressed at sites of neuroinflammation it is adopted as a biomarker of brain conditions. TSPO inhibits the autophagic removal of mitochondria by limiting PARK2-mediated mitochondrial ubiquitination via a peri-organelle accumulation of reactive oxygen species (ROS). Here we describe that TSPO deregulates mitochondrial Ca2+ signaling leading to a parallel increase in the cytosolic Ca2+ pools that activate the Ca2+-dependent NADPH oxidase (NOX) thereby increasing ROS. The inhibition of mitochondrial Ca2+ uptake by TSPO is a consequence of the phosphorylation of the voltage-dependent anion channel (VDAC1) by the protein kinase A (PKA), which is recruited to the mitochondria, in complex with the Acyl-CoA binding domain containing 3 (ACBD3). Notably, the neurotransmitter glutamate, which contributes neuronal toxicity in age-dependent conditions, triggers this TSPO-dependent mechanism of cell signaling leading to cellular demise. TSPO is therefore proposed as a novel OMM-based pathway to control intracellular Ca2+ dynamics and redox transients in neuronal cytotoxicity

The impact of uncertain precipitation data on insurance loss estimates using a flood catastrophe model

Catastrophe risk models used by the insurance industry are likely subject to significant uncertainty, but due to their proprietary nature and strict licensing conditions they are not available for experimentation. In addition, even if such experiments were conducted, these would not be repeatable by other researchers because commercial confidentiality issues prevent the details of proprietary catastrophe model structures from being described in public domain documents. However, such experimentation is urgently required to improve decision making in both insurance and reinsurance markets. In this paper we therefore construct our own catastrophe risk model for flooding in Dublin, Ireland, in order to assess the impact of typical precipitation data uncertainty on loss predictions. As we consider only a city region rather than a whole territory and have access to detailed data and computing resources typically unavailable to industry modellers, our model is significantly more detailed than most commercial products. The model consists of four components, a stochastic rainfall module, a hydrological and hydraulic flood hazard module, a vulnerability module, and a financial loss module. Using these we undertake a series of simulations to test the impact of driving the stochastic event generator with four different rainfall data sets: ground gauge data, gauge-corrected rainfall radar, meteorological reanalysis data (European Centre for Medium-Range Weather Forecasts Reanalysis-Interim; ERA-Interim) and a satellite rainfall product (The Climate Prediction Center morphing method; CMORPH). Catastrophe models are unusual because they use the upper three components of the modelling chain to generate a large synthetic database of unobserved and severe loss-driving events for which estimated losses are calculated. We find the loss estimates to be more sensitive to uncertainties propagated from the driving precipitation data sets than to other uncertainties in the hazard and vulnerability modules, suggesting that the range of uncertainty within catastrophe model structures may be greater than commonly believed

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

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

A woman living with osteoarthritis: A case report

Osteoarthritis is a common condition that is typically associated with older adults. Other causes of osteoarthritis, such as those cases resulting from childhood Perthes disease, can affect younger people and frequently have a major impact on the lives of those affected. This case report describes the experiences of one patient with osteoarthritis, using examples of her poetry to illustrate her social, psychological and emotional transformation

Generic bounds on dipolar gravitational radiation from inspiralling compact binaries

Various alternative theories of gravity predict dipolar gravitational radiation in addition to quadrupolar radiation. We show that gravitational wave (GW) observations of inspiralling compact binaries can put interesting constraints on the strengths of the dipole modes of GW polarizations. We put forward a physically motivated gravitational waveform for dipole modes, in the Fourier domain, in terms of two parameters: one which captures the relative amplitude of the dipole mode with respect to the quadrupole mode ($\alpha$) and the other a dipole term in the phase ($\beta$). We then use this two parameter representation to discuss typical bounds on their values using GW measurements. We obtain the expected bounds on the amplitude parameter $\alpha$ and the phase parameter $\beta$ for Advanced LIGO (AdvLIGO) and Einstein Telescope (ET) noise power spectral densities using Fisher information matrix. AdvLIGO and ET may at best bound $\alpha$ to an accuracy of $\sim10^{-2}$ and $\sim10^{-3}$ and $\beta$ to an accuracy of $\sim10^{-5}$ and $\sim10^{-6}$ respectively.Comment: Matches with the published versio

Forearm design for a myoelectric prosthetic hand

Due to the rapid growth of children and the complexity of myoelectric technology, children are often not given the same opportunities to use myoelectric prosthetics as adults. The Muscle Activated Prosthesis (MAP) team is working to create an affordable, transradial myoelectric prosthesis for a twelve-year-old girl. The basic mechanism by which this device operates is as follows: a muscle contraction emits an electrical signal that will be detected and processed through a microcontroller. Then the onboard software determines whether the hand opens or closes based on the level of muscle intensity. If the software determines to close or open the hand, a signal from the microcontroller is sent to linear actuators that control the tendon system running through the fingers. Currently the team has a working prototype that we plan to give to our client in the fall of 2020 to test.https://mosaic.messiah.edu/engr2020/1016/thumbnail.jp

In Silico Derivation of HLA-Specific Alloreactivity Potential from Whole Exome Sequencing of Stem Cell Transplant Donors and Recipients: Understanding the Quantitative Immuno-biology of Allogeneic Transplantation

Donor T cell mediated graft vs. host effects may result from the aggregate alloreactivity to minor histocompatibility antigens (mHA) presented by the HLA in each donor-recipient pair (DRP) undergoing stem cell transplantation (SCT). Whole exome sequencing has demonstrated extensive nucleotide sequence variation in HLA-matched DRP. Non-synonymous single nucleotide polymorphisms (nsSNPs) in the GVH direction (polymorphisms present in recipient and absent in donor) were identified in 4 HLA-matched related and 5 unrelated DRP. The nucleotide sequence flanking each SNP was obtained utilizing the ANNOVAR software package. All possible nonameric-peptides encoded by the non-synonymous SNP were then interrogated in-silico for their likelihood to be presented by the HLA class I molecules in individual DRP, using the Immune-Epitope Database (IEDB) SMM algorithm. The IEDB-SMM algorithm predicted a median 18,396 peptides/DRP which bound HLA with an IC50 of <500nM, and 2254 peptides/DRP with an IC50 of <50nM. Unrelated donors generally had higher numbers of peptides presented by the HLA. A similarly large library of presented peptides was identified when the data was interrogated using the Net MHCPan algorithm. These peptides were uniformly distributed in the various organ systems. The bioinformatic algorithm presented here demonstrates that there may be a high level of minor histocompatibility antigen variation in HLA-matched individuals, constituting an HLA-specific alloreactivity potential. These data provide a possible explanation for how relatively minor adjustments in GVHD prophylaxis yield relatively similar outcomes in HLA matched and mismatched SCT recipients.Comment: Abstract: 235, Words: 6422, Figures: 7, Tables: 3, Supplementary figures: 2, Supplementary tables: