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The evidence is strong in favor of blood pressure (BP) control in robust older people as a way to reduce morbidity and mortality in the same way that treatment improves the lives of middle-aged people. Expert editorials have been written over the last five decades persuasively arguing for or against more intensive treatment of older people with hypertension, supported by the specificity of (then) contemporaneous randomized controlled trials (RCTs) or the generalizability of observational studies. But there are limitations.First, there has always been such a thing as too low. Early epidemiological studies showed an upward inflection in mortality curves that resemble a slanted letter J. Second, certain complex older people encountered routinely in a clinic, pharmacy, or nursing facility were often excluded from the RCTs showing benefit from intensive BP control. Cohort studies of these complex people showed a different truth, that the point of “too low” might move up and that BP targets for adults might be too low for select older people. Not all older people are the same. Some are burdened by frailty superimposed on cardiovascular disease and a limited life-expectancy. It is one thing not to start BP-lowering medications for this patient; it is an entirely different matter to stop.

The problem of polypharmacy is complex, pervasive, and expanding. Appropriate prescribing of antihypertensive therapy for older people might help reduce medication burden, but it begins with a better understanding of what the evidence offers and where the evidence is quiet.In the first of this three-part series on antihypertensive medications for older people, we will trace the history of treating blood pressure with medication, from the expert opinion opposing treatment, to the observational data that led to paradigm shifts. We will follow the trail of evidence to randomized controlled trials (RCT) demonstrating the clear benefit of better control of blood pressure for all adults, regardless of age.RCT first evaluated any treatment against placebo, then began comparing one medication with another, and finally, more intensive control compared with less intensive control. Eventually professional societies bundled the evidence into guidelines to help busy prescribers and pharmacists wisely advise the consumers at the coal-face.In this first part of this series, we will present the evidence that favors intensive therapy in older people, that lower is better. In the second part, we will present evidence that highlights the dangers of going too low, and that stopping blood pressure-lowering medication might help. In the third part, we will discuss the evidence, new and old, that shows what happens when you stop.

The RIMFAX ground penetrating radar instrument on board the Mars 2020 Perseverance Rover has been continuously sounding the subsurface alongthe Rover traverse. In the data of the first 379 mission days on the Jezero Crater Floor we are able to identify hyperbolic patterns, likely caused by buried scatterers such as boulders or cavities in the upper 5 m of the subsurface. We present the first detailed estimates of radar wave propagation velocity by matching theoretical traveltime hyperbolas to the patterns generated by scatterers. The average dielectric permittivities are derived from these velocities and, consequently, the bulk rock densities for material above the scattering source. Simultaneously, we investigate the surface reflectivity to retrieve permittivity and density of the uppermost centimeter. Finally, we assess the radar attenuation by a constant-Q approach.The results are consistent with a solid rock, mafic interpretation of the Jezero Crater subsurface. The talk is based on the respective two most recent publications as well as work in progress.

Long-term hypertension control in the community significantly reduces cardiovascular risk. However, the benefit of controlling acute elevations of blood pressure in hospitalised patients is unclear. In-hospital elevations of blood pressure are relatively common and might not reflect poorly controlled blood pressure before admission. The measurement of blood pressure in hospital patients significantly differs from the best practice recommended for primary care and outpatients. Recent observational studies suggest that the pharmacological treatment of acute, asymptomatic, in-hospital elevations of blood pressure may have no benefit. However, it may increase the risk of in-hospital and post-discharge complications. Pending the development of robust inpatient measurement protocols, acute blood pressure elevations in hospitalised patients should not routinely require antihypertensive treatment in the absence of symptoms or acute end-organ damage. Rather, such elevations should facilitate follow-up of blood pressure and other cardiovascular risk factors after discharge.

The Radar Imager for Mars Subsurface Experiment instrument has conducted the first rover-mounted ground-penetrating radar survey of the Martian subsurface. A continuous radar image acquired over the Perseverance rover’s initial ~3-kilometer traverse reveals electromagnetic properties and bedrock stratigraphy of the Jezero crater floor to depths of ~15 meters below the surface. The radar image reveals the presence of ubiquitous strongly reflecting layered sequences that dip downward at angles of up to 15 degrees from horizontal in directions normal to the curvilinear boundary of and away from the exposed section of the Séitah formation. The observed slopes, thicknesses, and internal morphology of the inclined stratigraphic sections can be interpreted either as magmatic layering formed in a differentiated igneous body or as sedimentary layering commonly formed in aqueous environments on Earth. The discovery of buried structures on the Jezero crater floor is potentially compatible with a history of igneous activity and a history of multiple aqueous episodes.

Background Deprescribing may benefit older frail patients experiencing polypharmacy. We investigated the scope for deprescribing in acutely hospitalised patients and the long-term implications of continuation of medications that could potentially be deprescribed. Methods Acutely hospitalised patients (n = 170) discharged to Residential Aged Care Facilities, ≥75 years and receiving ≥5 regular medications were assessed during admission to determine eligibility for deprescribing of key drug classes, along with the actual incidence of deprescribing. The impact of continuation of nominated drug classes (anticoagulants, antidiabetics, antiplatelets, antipsychotics, benzodiazepines, proton pump inhibitors (PPIs), statins) on a combined endpoint (death/readmission) was determined. Results Hyperpolypharmacy (>10 regular medications) was common (49.4%) at admission. Varying rates of deprescribing occurred during hospitalisation for the nominated drug classes (8–53%), with considerable potential for further deprescribing (34–90%). PPI use was prevalent (56%) and 89.5% of these had no clear indication. Of the drug classes studied, only continued PPI use at discharge was associated with increased mortality/readmission at 1 year (hazard ratio 1.54, 95% confidence interval (1.06–2.26), P = 0.025), driven largely by readmission. Conclusion There is considerable scope for acute hospitalisation to act as a triage point for deprescribing in older patients. PPIs in particular appeared overprescribed in this susceptible patient group, and this was associated with earlier readmission. Polypharmacy in older hospitalised patients should be targeted for possible deprescribing during hospitalisation, especially PPIs.

Purpose Subcutaneous fentanyl injection is commonly prescribed to manage acute pain in older patients; however, there is a gap in the literature describing the pharmacokinetic parameters for this route of administration in this population. The aim of this study was to develop and evaluate a population pharmacokinetic model for subcutaneous fentanyl injection in older patients. Methods Twenty-one patients who received subcutaneous fentanyl injections (50 to 75 mu g) were recruited. Fentanyl concentrations were determined using a validated liquid chromatography/tandem mass spectrometry method. A population pharmacokinetic model was developed using non-linear mixed-effects modelling. A base model was selected based on the Akaike information criterion. Age, sex, body weight, number of previous fentanyl doses, number of prescribed medications, creatinine clearance, Charlson Comorbidity Index, Identification of Seniors at Risk score and concurrent use of CYP3A4 inhibitors were covariates considered for inclusion. A p value of < 0.05 was considered statistically significant for inclusion of covariates in the final model by stepwise addition. The simulation performance of the model was assessed by visual predictive check. Results A one-compartment, first-order absorption with lag time and linear elimination model was the best to fit to the fentanyl concentration data. The absorption rate constant was 0.136 h(-1) (between subject variability (BSV), 46%), lag time 0.66 h (BSV 51%), apparent volume of distribution 6.28 L (BSV 30%), and apparent clearance 16.3 L.h(-1) (BSV 54%). The Charlson Comorbidity Index was the only covariate included in the final model, where a higher value of the index increased fentanyl exposure and C-max. Conclusion This is the first report of subcutaneous fentanyl population pharmacokinetic model to evaluate fentanyl pharmacokinetic in older patients. The between subject variability in clearance and subcutaneous absorption rate was relatively high, and some patients recorded high fentanyl concentrations in the context of their titration to effect. Refereed/Peer-reviewed

The COVID-19 pandemic has had a substantial impact on the film industry in 2020. Films that tell the story of the pandemic by giving independent commentaries are important to our understanding of l...

Background Opioids are commonly prescribed to managing chronic pain in older persons. However, these patients are often at risk of drug-opioid interactions due to polypharmacy. Objectives To identify the prevalence of opioid prescribing and drug-opioid interactions in poly-medicated older patients and factors associated with opioid prescribing. Setting Patients were included if they were admitted to the Royal Adelaide Hospital between September 2015 and August 2016, aged ≥ 75 years and took ≥ 5 medications at discharge. Methods After ethics approval, data of were retrospectively collected from case notes. The Charlson Comorbidity Index and Drug Burden Index were determined and opioids were classified as strong or weak. The association between opioid use and concurrent medications was computed using logistic regression and the results presented as odds ratios (OR) and 95% confidence intervals (95% CI), adjusted for age, sex, Charlson Comorbidity Index, number of prescribed medications and modified-Drug Burden Index. Main outcome measure Association between concurrent medications and opioid prescribing. Results 15,000 geriatric admissions were identified, of which 1192 were included. A total of 283 (23.7%) patients were prescribed opioids, with oxycodone accounting for 56% of these prescriptions. Opioid users were prescribed more medications (11.2 vs. 9.0, P

A series of single-phase Fe-substituted hollandite (Ba,Cs)1.33(Fe,Ti)8O16 compositions with the chemical formula Ba1.33−xCsxFe2.66−xTi5.34+xO16 (x = 0, 0.1, 0.2, 0.667, and 1.33) were systematically investigated using both experimental and computational methods to establish possible links between crystal chemistry, Cs retention, thermochemistry and chemical durability. A phase transition from monoclinic to tetragonal was observed as a function of both Cs content and temperature. Elemental analysis revealed that Cs retention was significantly improved for the hollandite with higher Cs content. High-temperature melt solution calorimetry and sublattice-based thermodynamic simulations confirmed a high degree of thermodynamic stability in the Fe-substituted compounds which was enhanced in compositions with higher Cs content. This trend can be primarily attributed to two factors: (1) a decreasing ratio of the average ionic radii of B-site cations to that of A-site cations and (2) an increasing tolerance factor. Based on a reoptimized sublattice model, a pseudo-ternary phase diagram was generated to predict the optimal composition possessing the highest Cs content and A-site occupancy, which had not been experimentally explored. Leaching tests further verified that high Cs-containing compositions have significant chemical durability.

Accidental hypothermia can be fatal, and is often associated with confusion and paradoxical undressing. Wischnewski spots are a classic manifestation of hypothermia at autopsy., Wischnewski spots are a classic post‐mortem manifestation of accidental hypothermia. Clinical symptoms and signs of accidental hypothermia include agitation, confusion and paradoxical undressing.

Stack, K. et al., The Mars 2020 Perseverance rover landing site is located within Jezero crater, a ∼50km diameter impact crater interpreted to be a Noachian-aged lake basin inside the western edge of the Isidis impact structure. Jezero hosts remnants of a fluvial delta, inlet and outlet valleys, and infill deposits containing diverse carbonate, mafic, and hydrated minerals. Prior to the launch of the Mars 2020 mission, members of the Science Team collaborated to produce a photogeologic map of the Perseverance landing site in Jezero crater. Mapping was performed at a 1:5000 digital map scale using a 25 cm/pixel High Resolution Imaging Science Experiment (HiRISE) orthoimage mosaic base map and a 1 m/pixel HiRISE stereo digital terrain model. Mapped bedrock and surficial units were distinguished by differences in relative brightness, tone, topography, surface texture, and apparent roughness. Mapped bedrock units are generally consistent with those identified in previously published mapping efforts, but this study’s map includes the distribution of surficial deposits and sub-units of the Jezero delta at a higher level of detail than previous studies. This study considers four possible unit correlations to explain the relative age relationships of major units within the map area. Unit correlations include previously published interpretations as well as those that consider more complex interfingering relationships and alternative relative age relationships. The photogeologic map presented here is the foundation for scientific hypothesis development and strategic planning for Perseverance’s exploration of Jezero crater., With funding from the Spanish government through the "María de Maeztu Unit of Excellence" accreditation (MDM-2017-0737)

The Radar Imager for Mars’ Subsurface Experiment (RIMFAX) is a Ground Penetrating Radar on the Mars 2020 mission’sPerseverancerover, which is planned to land near a deltaic landform in Jezero crater. RIMFAX will add a new dimension to rover investigations of Mars by providing the capability to image the shallow subsurface beneath the rover. The principal goals of the RIMFAX investigation are to image subsurface structure, and to provide information regarding subsurface composition. Data provided by RIMFAX will aid Perseverance’s mission to explore the ancient habitability of its field area and to select a set of promising geologic samples for analysis, caching, and eventual return to Earth. RIMFAX is a Frequency Modulated Continuous Wave (FMCW) radar, which transmits a signal swept through a range of frequencies, rather than a single wide-band pulse. The operating frequency range of 150–1200 MHz covers the typical frequencies of GPR used in geology. In general, the full bandwidth (with effective center frequency of 675 MHz) will be used for shallow imaging down to several meters, and a reduced bandwidth of the lower frequencies (center frequency 375 MHz) will be used for imaging deeper structures. The majority of data will be collected at regular distance intervals whenever the rover is driving, in each of the deep, shallow, and surface modes. Stationary measurements with extended integration times will improve depth range and SNR at select locations. The RIMFAX instrument consists of an electronic unit housed inside the rover body and an antenna mounted externally at the rear of the rover. Several instrument prototypes have been field tested in different geological settings, including glaciers, permafrost sediments, bioherme mound structures in limestone, and sedimentary features in sand dunes. Numerical modelling has provided a first assessment of RIMFAX’s imaging potential using parameters simulated for the Jezero crater landing site.

Background: Pain is common in older patients and management guidelines rarely consider the effect of multiple comorbidities and concurrent medications on analgesic selection. Objectives: The objectives of this study were to identify the prevalence and pattern of analgesic prescribing and associated factors in older patients with polypharmacy. Methods: Older patients (aged ≥ 75 years) admitted to the Royal Adelaide Hospital between September 2015 and August 2016 and with polypharmacy were included and their comorbidities and medications prescribed at discharge were recorded. Drug Burden Index and Charlson Comorbidity Index were calculated. The number of medications that increased the risk of orthostatic hypotension were recorded. Logistic regression was used to compute the association between analgesic use and participant characteristics, and results were presented as odds ratios and 95% confidence intervals, adjusted for age, sex, Charlson Comorbidity Index, Drug Burden Index and orthostatic hypotension. Results: Over 15,000 admissions were identified, of which 1192 patients were included, 824 (69%) of whom were prescribed an analgesic medication. Paracetamol (used by 89% of analgesic users), opioids (34%) and adjuvants (17%) were used more frequently than non-steroidal anti-inflammatory drugs (8%). Analgesic users had a higher Drug Burden Index, were prescribed more medications and were less likely to be male compared with non-users. Charlson Comorbidity Index across the cohort was high (7.3 ± 1.9) but there was no difference between analgesic users and non-users, but analgesic users were more likely to have a documented diagnosis of osteoarthritis, osteoporosis and falls. Opioid use was associated with the Drug Burden Index, while adjuvant use was associated with orthostatic hypotension. Opioid use was associated with having a diagnosis of osteoporosis and falls. Conclusions: In our cohort of poly-medicated elderly patients, prescription of analgesic medications was common, and these patients are likely to have an increased rate of adverse drug reactions and falls compared with those who were not prescribed analgesic medications. Refereed/Peer-reviewed

This article describes the case of an older patient whose main presenting problem was depression. A constellation of clinical and biochemical features led to a search for medical causes of his low mood, which uncovered ectopic adrenocorticotropic hormone (ACTH) secretion. Post-mortem examination showed that the source of ACTH was small cell neuroendocrine carcinoma of the prostate, and that the patient had died from the sequelae of profound immune suppression.

Australian internal medicine trainees undergo intensive training in preparation for the Royal Australasian College of Physicians (RACP) clinical examination. Trainees preparing for the 2013 RACP clinical examination assessed the jugular venous pressure (JVP) of patients, with central venous pressure monitoring in the intensive care unit before and after the exam. RACP clinical examination preparation was associated with improvements of trainees' ability to identify JVP that were not elevated, although the JVP examination was performed marginally as a diagnostic test. Ongoing training might further improve this skill.

“Blast zones” (BZs) around new martian craters comprise various albedo features caused by the initial impact, including diffuse halos, extended linear and arcuate rays, secondary craters, ejecta patterns, and dust avalanches. We examined these features for changes in repeat images separated by up to four Mars years. Here we present the first comprehensive survey of the qualitative and quantitative changes observed in impact blast zones over time. Such changes are most likely due to airfall of high-albedo dust restoring darkened areas to their original albedo, the albedo of adjacent non-impacted surfaces. Although some sites show drastic changes over short timescales, nearly half of the sites show no obvious changes over several Mars years. Albedo changes are more likely to occur at higher-latitude sites, lower-elevation sites, and at sites with smaller central craters. No correlation was seen between amount of change and Dust Cover Index, relative halo size, or historical regional albedo changes. Quantitative albedo measurements of the diffuse dark halos relative to their surroundings yielded estimates of fading lifetimes for these features. The average lifetime among sites with measurable fading is ∼15 Mars years; the median is ∼8 Mars years for a linear brightening. However, at approximately half of sites with three or more repeat images, a nonlinear function with rapid initial fading followed by a slow increase in albedo provides a better fit to the fading behavior; this would predict even longer lifetimes. The predicted lifetimes of BZs are comparable to those of slope streaks, and considered representative of fading by global atmospheric dust deposition; they last significantly longer than dust devil or rover tracks, albedo features that are erased by different processes. These relatively long lifetimes indicate that the measurement of the current impact rate by Daubar et al. (Daubar, I.J. et al. [2013]. Icarus 225, 506–516. http://dx.doi.org/10.1016/j.icarus.2013.04.009 ) does not suffer significantly from overall under-sampling due to blast zones fading before new impact sites can be initially discovered. However, the prevalence of changes seen around smaller craters may explain in part their shallower size frequency distribution.