Health insurance - Fraser to Hawke : the introduction of Medicare

"The case study will analyse the health insurance policies during the Fraser and Hawke Governments, paying particular attention to the introduction of Medicare. The analysis will consider the development of the policy to introduce Medicare and the various factors that influenced its introduction. Although the models of policy analysis such as rationalism, incrementalism and group theory (Dye, 1978) will be applied, the critical factor public policy framework (Ryan, 1997) is the main tool that will be used to analyse the development, implementation and evaluation of this policy."--p. 2

Increased blood pressure variability following acute stroke is associated with poor long-term outcomes: a systematic review.

BACKGROUND: Blood pressure variability (BPV) in acute ischemic stroke (AIS) may be of prognostic significance. However, methodological heterogeneity of studies may contribute to inconsistent findings, and study findings are therefore not readily comparable. We investigated study methodologies which have assessed the long-term outcomes (≥7 days) of BPV post-AIS. MATERIALS AND METHODS: The literature search was conducted in OVID Medline, Embase, The Cochrane Library, and Web of Science following a predefined search strategy. Two reviewers independently assessed study eligibility and quality, and source data were extracted. RESULTS: Of 2044 studies identified, 19 observational studies and one case-control study were included; seven studies were additionally included. Twenty-two studies obtained good risk of bias ratings. Key findings were methodological heterogeneity and significant variability in the reporting of key criteria. Twenty-four studies reported intervals between blood pressure assessments; although 19 studies reported the monitoring device used, only eight studies reported the number of blood pressure measurements taken per visit. The majority measured supine blood pressure (n=13), and eight studies reported whether this was in the hemiparetic or unaffected arm. Sixteen studies defined BPV using SD and seven studies used only a single blood pressure parameter to quantify BPV. Increased BPV was associated with poorer neurological and functional outcomes, and death (n=23); other unfavorable outcomes included irregularly shaped lacunar infarcts, and impaired cognition (n=3). CONCLUSION: Methodological heterogeneity is frequently observed in studies, primarily because of incomplete study reporting. However, increased BPV is associated with adverse long-term outcomes. There is a need for prospective studies investigating BPV post-AIS to report full methodologies according to standardized criteria

Patient-derived explants (PDEs) as a powerful preclinical platform for anti-cancer drug and biomarker discovery

Preclinical models that can accurately predict outcomes in the clinic are much sought after in the field of cancer drug discovery and development. Existing models such as organoids and patient-derived xenografts have many advantages, but they suffer from the drawback of not contextually preserving human tumour architecture. This is a particular problem for the preclinical testing of immunotherapies, as these agents require an intact tumour human-specific microenvironment for them to be effective. In this review, we explore the potential of patient-derived explants (PDEs) for fulfilling this need. PDEs involve the ex vivo culture of fragments of freshly resected human tumours that retain the histological features of original tumours. PDE methodology for anti-cancer drug testing has been in existence for many years, but the platform has not been widely adopted in translational research facilities, despite strong evidence for its clinical predictivity. By modifying PDE endpoint analysis to include the spatial profiling of key biomarkers by using multispectral imaging, we argue that PDEs offer many advantages, including the ability to correlate drug responses with tumour pathology, tumour heterogeneity and changes in the tumour microenvironment. As such, PDEs are a powerful model of choice for cancer drug and biomarker discovery programmes

The rationale and design of a cross-sectional study to investigate and describe the Chronotype of Patients with Type 2 Diabetes and the Effect on Glycaemic Control: The CODEC study

Introduction A person’s chronotype is their entrained preference for sleep time within the 24-hour clock. It is described by the well-known concept of the ‘lark’ (early riser) and ‘owl’ (late sleeper). Evidence suggests that the ‘owl’ is metabolically disadvantaged due to the standard organisation of our society which favours the ‘lark’ and places physiological stresses on this chronotype. The aim of this study is to explore cardiometabolic health between the lark and owl in a population with an established metabolic condition - Type 2 Diabetes. Methods This cross-sectional, multi-site study aims to recruit 2247 participants from both secondary and primary care settings. The primary objective is to compare glycaemic control between late and early chronotypes. Secondary objectives include determining if late-chronotype is associated with poorer cardiometabolic health and other lifestyle factors, including well-being, compared to early-chronotype; describing the prevalence of the five different chronotypes in this cohort and examining the trends in glycaemic control, cardiometabolic health, well-being and lifestyle factors across chronotype. Analysis The primary outcome (HbA1c), linear regression analysis will compare HbA1c between early and late chronotypes, with and without adjustment for confounding variables. Chronotype will be modelled as a categorical variable with all five levels (from extreme-morning to extremelate type), and as a continuous variable to calculate p for trend across the five categories. A number of models will be created; unadjusted through to adjusted with age, sex, ethnicity, BMI, duration of diabetes, family history of diabetes, current medication and dietary habits. All secondary outcomes will be analysed using the same method. Ethics Ethical approval from the West Midlands - Black Country Research Ethics Committee (16/WM/0457). Dissemination The results will be disseminated through publication in peer reviewed medical journal, relevant medical/health conferences and a summary report sent to patients. Registration details Registered on clinicaltrials.gov NCT02973412 (23.11.20116

VLBI observations of GRB 201015A, a relatively faint GRB with a hint of very high-energy gamma-ray emission

Context. A total of four long-duration gamma-ray bursts (GRBs) have been confirmed at very high-energy (≥100GeV) with high significance, and any possible peculiarities of these bursts will become clearer as the number of detected events increases. Multi-wavelength follow-up campaigns are required to extract information on the physical conditions within the jets that lead to the very high-energy counterpart, hence they are crucial to reveal the properties of this class of bursts. Aims. GRB 201015A is a long-duration GRB detected using the MAGIC telescopes from ~40 s after the burst. If confirmed, this would be the fifth and least luminous GRB ever detected at these energies. The goal of this work is to constrain the global and microphysical parameters of its afterglow phase, and to discuss the main properties of this burst in a broader context. Methods. Since the radio band, together with frequent optical and X-ray observations, proved to be a fundamental tool for overcoming the degeneracy in the afterglow modelling, we performed a radio follow-up of GRB 201015A over 12 different epochs, from 1.4 days (2020 October 17) to 117 days (2021 February 9) post-burst, with the Karl G. Jansky Very Large Array, e-MERLIN, and the European VLBI Network. We include optical and X-ray observations, performed respectively with the Multiple Mirror Telescope and the Chandra X-ray Observatory, together with publicly available data, in order to build multi-wavelength light curves and to compare them with the standard fireball model. Results. We detected a point-like transient, consistent with the position of GRB 201015A until 23 and 47 days post-burst at 1.5 and 5 GHz, respectively. No emission was detected in subsequent radio observations. The source was also detected in optical (1.4 and 2.2 days post-burst) and in X-ray (8.4 and 13.6 days post-burst) observations. Conclusions. The multi-wavelength afterglow light curves can be explained with the standard model for a GRB seen on-axis, which expands and decelerates into a medium with a homogeneous density. A circumburst medium with a wind-like profile is disfavoured. Notwithstanding the high resolution provided by the VLBI, we could not pinpoint any expansion or centroid displacement of the outflow. If the GRB is seen at the viewing angle θ that maximises the apparent velocity βapp (i.e. θ ~ βapp-1), we estimate that the Lorentz factor for the possible proper motion is Гα ≤ 40 in right ascension and Гδ ≤ 61 in declination. On the other hand, if the GRB is seen on-axis, the size of the afterglow is ≤5pc and ≤16pc at 25 and 47 days. Finally, the early peak in the optical light curve suggests the presence of a reverse shock component before 0.01 days from the burst

CompreHensive geriAtRician-led MEdication Review (CHARMER): protocol for a feasibility study of a hospital deprescribing behaviour change intervention

Introduction Over 50% of older adults are prescribed a medicine where the risk of harm outweighs the chances of benefit. During a hospital admission, older adults and carers expect medicines to be reviewed for appropriateness and any inappropriate medicines proactively deprescribed. While the principle of proactive deprescribing is an expectation of good prescribing practice, it is yet to become routine. The CompreHensive geriAtRician-led MEdication Review (CHARMER) study aims to develop and test a five-component behaviour change intervention to equip geriatricians and pharmacists to proactively deprescribe inappropriate medicines with older adults in hospital. This study aims to test the feasibility and acceptability of study processes and CHARMER implementation. Methods and analysis A two-arm purposive allocation feasibility study is being undertaken at four acute hospitals in England, UK (three intervention and one control). The target sample is 400 patients across all hospitals. Primary outcome measures are: (1) participant recruitment rate and (2) participant attrition rate. Secondary outcome measures are: (1) hospital readmission rate; (2) mortality rate and (3) quality of life. Quantitative data will be checked for completeness and quality, and practitioner and patient demographics descriptively analysed. We will undertake a rapid qualitative analysis on observations, interviews and study meeting minutes data. A subsequent thematic analysis will be undertaken with codes mapped to the Theoretical Domains Framework and Normalisation Process Theory. Triangulation of qualitative and quantitative data will be undertaken. Ethics and dissemination Ethics approval was obtained from Wales Research Ethics Committee 1 (IRAS ID 312494) and study approval from the Health Research Authority (22/WA/0087). Informed consent will be sought from all hospital staff involved in data collection activities and for patients involved in enhanced data collection activities. The findings of this study will be disseminated in peer-reviewed journals and conference presentations.</p

GRB 201015A and the nature of low-luminosity soft gamma-ray bursts

GRB 201015A is a peculiarly low luminosity, spectrally soft gamma-ray burst (GRB), with T90 = 9.8 ± 3.5 s (time interval of detection of 90  per cent of photons from the GRB), and an associated supernova (likely to be type Ic or Ic-BL). GRB 201015A has an isotropic energy Eγ,iso =1.75+0.60−0.53×1050  erg, and photon index Γ=3.00+0.50−0.42  (15–150 keV). It follows the Amati relation, a correlation between Eγ,iso  and spectral peak energy Ep followed by long GRBs. It appears exceptionally soft based on Γ, the hardness ratio of HR  = 0.47 ± 0.24, and low-Ep, so we have compared it to other GRBs sharing these properties. These events can be explained by shock breakout, poorly collimated jets, and off-axis viewing. Follow-up observations of the afterglow taken in the X-ray, optical, and radio reveal a surprisingly late flattening in the X-ray from t = (2.61 ± 1.27) × 104 s to t=1.67+1.14−0.65×106  s. We fit the data to closure relations describing the synchrotron emission, finding the electron spectral index to be p=2.42+0.44−0.30  and evidence of late-time energy injection with coefficient q=0.24+0.24−0.18 ⁠. The jet half opening angle lower limit (θj ≥ 16°) is inferred from the non-detection of a jet break. The launch of SVOM and Einstein Probe in 2023 should enable detection of more low-luminosity events like this, providing a fuller picture of the variety of GRBs.</p

Dipeptidyl peptidase-1 inhibition in patients hospitalised with COVID-19: a multicentre, double-blind, randomised, parallel-group, placebo-controlled trial

Background Neutrophil serine proteases are involved in the pathogenesis of COVID-19 and increased serine protease activity has been reported in severe and fatal infection. We investigated whether brensocatib, an inhibitor of dipeptidyl peptidase-1 (DPP-1; an enzyme responsible for the activation of neutrophil serine proteases), would improve outcomes in patients hospitalised with COVID-19. Methods In a multicentre, double-blind, randomised, parallel-group, placebo-controlled trial, across 14 hospitals in the UK, patients aged 16 years and older who were hospitalised with COVID-19 and had at least one risk factor for severe disease were randomly assigned 1:1, within 96 h of hospital admission, to once-daily brensocatib 25 mg or placebo orally for 28 days. Patients were randomly assigned via a central web-based randomisation system (TruST). Randomisation was stratified by site and age (65 years or ≥65 years), and within each stratum, blocks were of random sizes of two, four, or six patients. Participants in both groups continued to receive other therapies required to manage their condition. Participants, study staff, and investigators were masked to the study assignment. The primary outcome was the 7-point WHO ordinal scale for clinical status at day 29 after random assignment. The intention-to-treat population included all patients who were randomly assigned and met the enrolment criteria. The safety population included all participants who received at least one dose of study medication. This study was registered with the ISRCTN registry, ISRCTN30564012. Findings Between June 5, 2020, and Jan 25, 2021, 406 patients were randomly assigned to brensocatib or placebo; 192 (47·3%) to the brensocatib group and 214 (52·7%) to the placebo group. Two participants were excluded after being randomly assigned in the brensocatib group (214 patients included in the placebo group and 190 included in the brensocatib group in the intention-to-treat population). Primary outcome data was unavailable for six patients (three in the brensocatib group and three in the placebo group). Patients in the brensocatib group had worse clinical status at day 29 after being randomly assigned than those in the placebo group (adjusted odds ratio 0·72 [95% CI 0·57–0·92]). Prespecified subgroup analyses of the primary outcome supported the primary results. 185 participants reported at least one adverse event; 99 (46%) in the placebo group and 86 (45%) in the brensocatib group. The most common adverse events were gastrointestinal disorders and infections. One death in the placebo group was judged as possibly related to study drug. Interpretation Brensocatib treatment did not improve clinical status at day 29 in patients hospitalised with COVID-19.</p

The Gravitational-wave Optical Transient Observer (GOTO): Prototype performance and prospects for transient science

The Gravitational-wave Optical Transient Observer (GOTO) is an array of wide-field optical telescopes, designed to exploit new discoveries from the next generation of gravitational wave detectors (LIGO, Virgo, and KAGRA), study rapidly evolving transients, and exploit multimessenger opportunities arising from neutrino and very high energy gamma-ray triggers. In addition to a rapid response mode, the array will also perform a sensitive, all-sky transient survey with few day cadence. The facility features a novel, modular design with multiple 40-cm wide-field reflectors on a single mount. In 2017 June, the GOTO collaboration deployed the initial project prototype, with 4 telescope units, at the Roque de los Muchachos Observatory (ORM), La Palma, Canary Islands. Here, we describe the deployment, commissioning, and performance of the prototype hardware, and discuss the impact of these findings on the final GOTO design. We also offer an initial assessment of the science prospects for the full GOTO facility that employs 32 telescope units across two sites