Evaluation of the incremental cost to the National Health Service of prescribing analogue insulin

Introduction Insulin analogues have become increasingly popular despite their greater cost compared with human insulin. The aim of this study was to calculate the incremental cost to the National Health Service (NHS) of prescribing analogue insulin preparations instead of their human insulin alternatives. Methods Open-source data from the four UK prescription pricing agencies from 2000 to 2009 were analysed. Cost was adjusted for inflation and reported in UK pounds at 2010 prices. Results Over the 10-year period, the NHS spent a total of £2732 million on insulin. The total annual cost increased from £156 million to £359 million, an increase of 130%. The annual cost of analogue insulin increased from £18.2 million (12% of total insulin cost) to £305 million (85% of total insulin cost), whereas the cost of human insulin decreased from £131 million (84% of total insulin cost) to £51 million (14% of total insulin cost). If it is assumed that all patients using insulin analogues could have received human insulin instead, the overall incremental cost of analogue insulin was £625 million. Conclusion Given the high marginal cost of analogue insulin, adherence to prescribing guidelines recommending the preferential use of human insulin would have resulted in considerable financial savings over the period

Deriving health state utilities for the numerical pain rating scale

Background The use of patient reported outcome measures within cost-effectiveness analysis has become commonplace. However, specific measures are required that produce values, referred to as 'utilities', that are capable of generating quality adjusted life years. One such measure - the EQ-5D - has come under criticism due to the inherent limitations of its three-level response scales. In evaluations of chronic pain, the numerical pain rating scale (NPRS) which has eleven levels is routinely used which has a greater measurement range, but which can not be used in cost-effetiveness analyses. This study derived utility values for a series of EQ-5D health states that replace the pain dimensions with the NPRS, thereby allowing a potentially greater range of pain intensities to be captured and included in economic analyses. Methods Interviews were undertaken with 100 member of the general population. Health state valuations were elicited using the time trade-off approach with a ten year time horizon. Additionally, respondents were asked where the EQ-5D response scale descriptors of moderate and extreme pain lay on the 11-point NPRS scale. Results 625 valuations were undertaken across the study sample with the crude mean health state utilities showing a negative non-linear relationship with respect to increasing pain intensity. Relative to a NPRS of zero (NPRS0), the successive pain levels (NPRS1-10) had mean decrements in utility of 0.034, 0.043, 0.061, 0.121, 0.144, 0.252, 0.404, 0.575, 0.771 and 0.793, respectively. When respondents were asked to mark on the NPRS scale the EQ-5D pain descriptors of moderate and extreme pain, the median responses were '4' and '8', respectively. Conclusions These results demonstrate the potential floor effect of the EQ-5D with respect to pain and provide estimates of health reduction associated with pain intensity described by the NPRS. These estimates are in excess of the decrements produced by an application of the EQ-5D scoring tariff for both the United States and the United Kingdom

Effects of the visual environment on object localization in posterior cortical atrophy and typical Alzheimer's disease

Introduction: Visual processing deficits in Alzheimer's disease are associated with diminished functional independence. While environmental adaptations have been proposed to promote independence, recent guidance gives limited consideration to such deficits and offers conflicting recommendations for people with dementia. We evaluated the effects of clutter and color contrasts on performances of everyday actions in posterior cortical atrophy and memory-led typical Alzheimer's disease. Methods: 15 patients with posterior cortical atrophy, 11 with typical Alzheimer's disease and 16 healthy controls were asked to pick up a visible target object as part of two pilot repeated-measures investigations from a standing or seated position. Participants picked up the target within a controlled real-world setting under varying environmental conditions: with/without clutter, with/without color contrast cue and far/near target position. Task completion time was recorded using a target-mounted inertial measurement unit. Results: Across both experiments, difficulties locating a target object were apparent through patient groups taking an estimated 50–90% longer to pick up targets relative to controls. There was no evidence of effects of color contrast when locating objects from standing/seated positions and of any other environmental conditions from a standing position on completion time in any participant group. Locating objects, surrounded by five distractors rather than none, from a seated position was associated with a disproportionately greater effect on completion times in the posterior cortical atrophy group relative to the control or typical Alzheimer's disease groups. Smaller, not statistically significant but directionally consistent, ratios of relative effects were seen for two distractors compared with none. Discussion: Findings are consistent with inefficient object localization in posterior cortical atrophy relative to typical Alzheimer's disease and control groups, particularly with targets presented within reaching distance among visual clutter. Findings may carry implications for considering the adverse effects of visual clutter in developing and implementing environmental modifications to promote functional independence in Alzheimer's disease

Effectiveness of the capsaicin 8% patch in the management of peripheral neuropathic pain in European clinical practice: the ASCEND study

Background In randomised studies, the capsaicin 8% patch has demonstrated effective pain relief in patients with peripheral neuropathic pain (PNP) arising from different aetiologies. Methods ASCEND was an open-label, non-interventional study of patients with non-diabetes-related PNP who received capsaicin 8% patch treatment, according to usual clinical practice, and were followed for ≤52 weeks. Co-primary endpoints were percentage change in the mean numeric pain rating scale (NPRS) ‘average daily pain’ score from baseline to the average of Weeks 2 and 8 following first treatment; and median time from first to second treatment. The primary analysis was intended to assess analgesic equivalence between post-herpetic neuralgia (PHN) and other PNP aetiologies. Health-related quality of life (HRQoL, using EQ-5D), Patient Global Impression of Change (PGIC) and tolerability were also assessed. Results Following first application, patients experienced a 26.6% (95% CI: 23.6, 29.62; n = 412) reduction in mean NPRS score from baseline to Weeks 2 and 8. Equivalence was demonstrated between PHN and the neuropathic back pain, post-operative and post-traumatic neuropathic pain and ‘other’ PNP aetiology subgroups. The median time from first to second treatment was 191 days (95% CI: 147, 235; n = 181). Forty-four percent of all patients were responders (≥30% reduction in NPRS score from baseline to Weeks 2 and 8) following first treatment, and 86.9% (n = 159/183) remained so at Week 12. A sustained pain response was observed until Week 52, with a 37.0% (95% CI: 31.3, 42.7; n = 176) reduction in mean NPRS score from baseline. Patients with the shortest duration of pain (0–0.72 years) experienced the highest pain response from baseline to Weeks 2 and 8. Mean EQ-5D index score improved by 0.199 utils (responders: 0.292 utils) from baseline to Week 2 and was maintained until Week 52. Most patients reported improvements in PGIC at Week 2 and at all follow-up assessments regardless of number of treatments received. Adverse events were primarily mild or moderate reversible application site reactions. Conclusion In European clinical practice, the capsaicin 8% patch provided effective and sustained pain relief, substantially improved HRQoL, improved overall health status and was generally well tolerated in a heterogeneous PNP population

Governing the UN Sustainable Development Goals: Interactions, Infrastructures, and Institutions

Three of the eight Millennium Development Goals (MDGs) concerned health. There is only one health goal in 17 proposed Sustainable Development Goals (SDGs). Critiques of the MDGs included missed opportunities to realise positive interactions between goals. Here we report on an interdisciplinary analytical review of the SDG process, in which experts in different SDG areas identified potential interactions through a series of interdisciplinary workshops. This process generated a framework that reveals potential conflicts and synergies between goals, and how their interactions might be governed

Estimation of health-related utility (EQ-5D index) in subjects with seasonal allergic rhinoconjunctivitis to evaluate health gain associated with sublingual grass allergen immunotherapy

Abstract Background: Grass allergen immunotherapy (AIT) reduces symptom severity in seasonal allergic rhinoconjunctivitis (ARC) but its impact on general health-related utility has not been characterised for the purposes of economic evaluation. The aim of this study was to model the preferred measure of utility, EQ-5D index, from symptom severity and estimate incremental quality adjusted life years (QALYs) associated with SQ-standardised grass immunotherapy tablet (GRAZAX®, 75,000 SQ-T/2,800 BAU, ALK, Denmark). Methods: Data were analysed from five consecutive pollen seasons in a randomised placebo controlled trial of GRAZAX®. Binomial and Gaussian mixed effects modelling related weekly EQ-5D index score to daily symptom and medication scores (DSS & DMS respectively). In turn, daily EQ-5D index was estimated from ARC symptoms and medication use

Fatal Canine Intoxications Linked to the Presence of Saxitoxins in Stranded Marine Organisms Following Winter Storm Activity.

At the start of 2018, multiple incidents of dog illnesses were reported following consumption of marine species washed up onto the beaches of eastern England after winter storms. Over a two-week period, nine confirmed illnesses including two canine deaths were recorded. Symptoms in the affected dogs included sickness, loss of motor control, and muscle paralysis. Samples of flatfish, starfish, and crab from the beaches in the affected areas were analysed for a suite of naturally occurring marine neurotoxins of dinoflagellate origin. Toxins causing paralytic shellfish poisoning (PSP) were detected and quantified using two independent chemical testing methods in samples of all three marine types, with concentrations over 14,000 µg saxitoxin (STX) eq/kg found in one starfish sample. Further evidence for PSP intoxication of the dogs was obtained with the positive identification of PSP toxins in a vomited crab sample from one deceased dog and in gastrointestinal samples collected post mortem from a second affected dog. Together, this is the first report providing evidence of starfish being implicated in a PSP intoxication case and the first report of PSP in canines

Characterization and Associated Costs of Constipation Relating to Exposure to Strong Opioids in England: An Observational Study

PurposeOpioid use is associated with gastrointestinal adverse events, including nausea and constipation. We used a real-world dataset to characterize the health care burden associated with opioid-induced constipation (OIC) with particular emphasis on strong opioids.MethodsThis retrospective cohort study was conducted using the Clinical Practice Research Datalink, a large UK primary care dataset linked to hospital data. Patients prescribed opioids during 2016 were selected and episodes of opioid therapy constructed. Episodes with ≥84 days of exposure were classified as chronic, with date of first prescription as the index date. The main analysis focused on patients prescribed strong opioids who were laxative naive. Constipation was defined by ≥2 laxative prescriptions during the opioid episode. Patients for whom initial laxative therapy escalated by switch, augmentation, or dose were defined as OIC unstable, and the first 3 lines of OIC escalation were classified. Health care costs accrued in the first 12 months of the opioid episode were aggregated and compared.FindingsA total of 27,629 opioid episodes were identified; 5916 (21.4%) involved a strong opioid for patients who were previously laxative naive. Of these patients, 2886 (48.8%) were defined as the OIC population; 941 (33.26%) were classified as stable. Of the 1945 (67.4%) episodes classified as unstable, 849 (43.7%), 360 (18.5%), and 736 (37.8%) had 1, 2, and ≥3 changes of laxative prescription, respectively. Patients without OIC had lower costs per patient year (£3822 [US$5160/€4242]) compared with OIC (£4786 [US$6461/€5312]). Costs increased as patients had multiple changes in therapy: £4696 (US$6340/€5213), £4749 (US$6411/€5271), and £4981 (US$6724/€5529) for 1, 2, and ≥3 changes, respectively. The adjusted cost ratio relative to non-OIC was 1.14 (95$5031/€4137] vs £2379 [US$3212 /€2641),and for those patients classified as unstable versus stable (£3931 [US$5307/€4363] vs £3432 [US$4633/€3810). Costs increased with each additional line of therapy from £3701 (US$4996/€4108), £3916 (US$5287/€4347), and £4318 (US$5829/€4793).ImplicationsOIC was a common adverse event of opioid treatment and was poorly controlled for a large number of patients. Poor control was associated with increased health care costs. The impact of OIC should be considered when prescribing opioids. These results should be interpreted with consideration of the caveats associated with the analysis of routine data

The WiggleZ Dark Energy Survey: Star-formation in UV-luminous galaxies from their luminosity functions

We present the ultraviolet (UV) luminosity function of galaxies from the GALEX Medium Imaging Survey with measured spectroscopic redshifts from the first data release of the WiggleZ Dark Energy Survey. This sample selects galaxies with high star formation rates: at 0.6 < z < 0.9 the median star formation rate is at the upper 95th percentile of optically-selected (r<22.5) galaxies and the sample contains about 50 per cent of all NUV < 22.8, 0.6 < z < 0.9 starburst galaxies within the volume sampled. The most luminous galaxies in our sample (-21.0>M_NUV>-22.5) evolve very rapidly with a number density declining as (1+z)^{5\pm 1} from redshift z = 0.9 to z = 0.6. These starburst galaxies (M_NUV<-21 is approximately a star formation rate of 30 \msuny) contribute about 1 per cent of cosmic star formation over the redshift range z=0.6 to z=0.9. The star formation rate density of these very luminous galaxies evolves rapidly, as (1+z)^{4\pm 1}. Such a rapid evolution implies the majority of star formation in these large galaxies must have occurred before z = 0.9. We measure the UV luminosity function in 0.05 redshift intervals spanning 0.1<z<0.9, and provide analytic fits to the results. At all redshifts greater than z=0.55 we find that the bright end of the luminosity function is not well described by a pure Schechter function due to an excess of very luminous (M_NUV<-22) galaxies. These luminosity functions can be used to create a radial selection function for the WiggleZ survey or test models of galaxy formation and evolution. Here we test the AGN feedback model in Scannapieco et al. (2005), and find that this AGN feedback model requires AGN feedback efficiency to vary with one or more of the following: stellar mass, star formation rate and redshift.Comment: 27 pages; 13 pages without appendices. 22 figures; 11 figures in the main tex

The WiggleZ Dark Energy Survey: improved distance measurements to z = 1 with reconstruction of the baryonic acoustic feature

We present significant improvements in cosmic distance measurements from the WiggleZ Dark Energy Survey, achieved by applying the reconstruction of the baryonic acoustic feature technique. We show using both data and simulations that the reconstruction technique can often be effective despite patchiness of the survey, significant edge effects and shot-noise. We investigate three redshift bins in the redshift range 0.2 < z < 1, and in all three find improvement after reconstruction in the detection of the baryonic acoustic feature and its usage as a standard ruler. We measure model-independent distance measures DV(rsfid/rs) of 1716 ± 83, 2221 ± 101, 2516 ± 86 Mpc (68 per cent CL) at effective redshifts z = 0.44, 0.6, 0.73, respectively, where DV is the volume-averaged distance, and rs is the sound horizon at the end of the baryon drag epoch. These significantly improved 4.8, 4.5 and 3.4 per cent accuracy measurements are equivalent to those expected from surveys with up to 2.5 times the volume of WiggleZ without reconstruction applied. These measurements are fully consistent with cosmologies allowed by the analyses of the Planck Collaboration and the Sloan Digital Sky Survey. We provide the DV(rsfid/rs) posterior probability distributions and their covariances. When combining these measurements with temperature fluctuations measurements of Planck, the polarization of Wilkinson Microwave Anisotropy Probe 9, and the 6dF Galaxy Survey baryonic acoustic feature, we do not detect deviations from a flat Λ cold dark matter (ΛCDM) model. Assuming this model, we constrain the current expansion rate to H₀ = 67.15 ± 0.98 km s⁻¹Mpc⁻¹. Allowing the equation of state of dark energy to vary, we obtain wDE = −1.080 ± 0.135. When assuming a curved ΛCDM model we obtain a curvature value of ΩK = −0.0043 ± 0.0047