Influence of medication risks and benefits on treatment preferences in older patients with multimorbidity

Multimorbidity is associated with use of multiple medicines, increased risk of adverse events and treatment conflicts. This study aimed to examine how older patients with multimorbidity and clinicians balance the benefits and harms associated with a medication and in the presence of competing health outcomes. Interviews were conducted with 15 participants aged ≥65 years with 2 or more chronic conditions. Three clinical scenarios were presented to understand patient preference to take a medicine according to i) degree of benefit, ii) type of adverse event and impact on daily living and iii) influence of comorbid conditions as competing health outcomes. Semi-structured interviews were also conducted with participants (n=15) and clinicians (n=5) to understand patient preferences and treatment decisions, in the setting of multimorbidity. The median age of participants was 79 years, 55% had 5 or more conditions and 47% took 8 or more medicines daily. When the level of benefit of the medicine ranged from 14% to 70%, 80% of participants chose to take the medicine, but when adverse effects were present, this was reduced to 0-33% depending upon impact on daily activities. In the presence of competing health outcomes, 13%-26% of patients chose to take the medicine. Two-thirds of patients reported that their doctor respects and considers their preferences and discussed medication benefits and harms. Interviews with clinicians showed that their overall approach to treatment decision-making for older individuals with multimorbidity was based upon 2 main factors, the patients' prognosis and their preferences. The degree of benefit gained was not the driver of patients' preference to take a medicine; rather, this decision was influenced by type and severity of adverse effects. Inclusion of patient preferences in the setting of risks and benefits of medicines with consideration and prioritization of competing health outcomes may result in improved health outcomes for people with multimorbidity.Gillian E Caughey, Kirsty Tait, Agnes I Vitry, Sepehr Shaki

A dedicated haem lyase is required for the maturation of a novel bacterial cytochrome c with unconventional covalent haem binding

In bacterial c-type cytochromes, the haem cofactor is covalently attached via two cysteine residues organized in a haem c-binding motif. Here, a novel octa-haem c protein, MccA, is described that contains only seven conventional haem c-binding motifs (CXXCH), in addition to several single cysteine residues and a conserved CH signature. Mass spectrometric analysis of purified MccA from Wolinella succinogenes suggests that two of the single cysteine residues are actually part of an unprecedented CX15CH sequence involved in haem c binding. Spectroscopic characterization of MccA identified an unusual high-potential haem c with a red-shifted absorption maximum, not unlike that of certain eukaryotic cytochromes c that exceptionally bind haem via only one thioether bridge. A haem lyase gene was found to be specifically required for the maturation of MccA in W. succinogenes. Equivalent haem lyase-encoding genes belonging to either the bacterial cytochrome c biogenesis system I or II are present in the vicinity of every known mccA gene suggesting a dedicated cytochrome c maturation pathway. The results necessitate reconsideration of computer-based prediction of putative haem c-binding motifs in bacterial proteomes

Occurrence and specificity of glucose oxidase (E.C: 1.1.3.4) in botrytized sweet white wine. Comparison with laccase (E.C: 1.10.3.2), considered as the main responsible factor for oxidation in this type of wine

Two types of oxidizing enzymes are present in botrytized white grapes and wines: laccase (PPO) and glucose oxidase (GOX). The evolution of these two enzymes is similar both during the over-ripening of grapes and during wine making. Yet, PPO is severely inhibited by the addition of SO2 following the alcoholic fermentation, and shows a marked instability in both the must and wine environments. GOX, however, remains free and active in solution and helps develop the main characteristics of the wine. In particular, as is to be expected from its activity, GOX oxidizes tartaric acid, ethanol and glycerol, the major components of must and wine, respectively to glyoxylic acid, acetaldehyde and glyceraldehyde. And then, by nucleophilic additions under acidic conditions, these products react with catechins and proanthocyanidins to form several new compounds, some of which appear in a colored form. These reactions can have an impact on the visual quality of the wine.

FLOOD-WATER LEVEL ESTIMATION FROM SOCIAL MEDIA IMAGES

In the event of a flood, being able to build accurate flood level maps is essential for supporting emergency plan operations. In order to build such maps, it is important to collect observations from the disaster area. Social media platforms can be useful sources of information in this case, as people located in the flood area tend to share text and pictures depicting the current situation. Developing an effective and fully automatized method able to retrieve data from social media and extract useful information in real-time is crucial for a quick and proper response to these catastrophic events. In this paper, we propose a method to quantify flood-water from images gathered from social media. If no prior information about the zone where the picture was taken is available, one possible way to estimate the flood level consists of assessing how much the objects appearing in the image are submerged in water. There are various factors that make this task difficult: i) the precise size of the objects appearing in the image might not be known; ii) flood-water appearing in different zones of the image scene might have different height; iii) objects may be only partially visible as they can be submerged in water. In order to solve these problems, we propose a method that first locates selected classes of objects whose sizes are approximately known, then, it leverages this property to estimate the water level. To prove the validity of this approach, we first build a flood-water image dataset, then we use it to train a deep learning model. We finally show the ability of our trained model to recognize objects and at the same time predict correctly flood-water level

Eliciting a predatory response in the eastern corn snake (Pantherophis guttatus) using live and inanimate sensory stimuli: implications for managing invasive populations

North America's Eastern corn snake (Pantherophis guttatus) has been introduced to several islands throughout the Caribbean and Australasia where it poses a significant threat to native wildlife. Invasive snake control programs often involve trapping with live bait, a practice that, as well as being costly and labour intensive, raises welfare and ethical concerns. This study assessed corn snake response to live and inanimate sensory stimuli in an attempt to inform possible future trapping of the species and the development of alternative trap lures. We exposed nine individuals to sensory cues in the form of odour, visual, vibration and combined stimuli and measured the response (rate of tongue-flick [RTF]). RTF was significantly higher in odour and combined cues treatments, and there was no significant difference in RTF between live and inanimate cues during odour treatments. Our findings suggest chemical cues are of primary importance in initiating predation and that an inanimate odour stimulus, absent of simultaneous visual and vibratory cues, is a potential low-cost alternative trap lure for the control of invasive corn snake populations

Spatiotemporal trends in cetacean strandings and response in the southwestern Indian Ocean : 2000–2020

On behalf of SIF, we would like to thank the Seychelles partners (Alphonse Foundation, Desroches Foundation, Island Conservation Society, Farquhar Foundation, Seychelles Islands Foundation, Silhouette Foundation) for providing financial support to acquire and grant use of their data. Collection of data in Reunion was funded by DEAL Reunion and Region-Reunion.The south-western Indian Ocean (SWIO) is a region of global importance for marine mammal biodiversity, but our understanding of most of the species and populations found there is still rudimentary. The Indian Ocean Network for Cetacean Research (IndoCet) was formed in 2014 and is dedicated to the research of all cetacean species across the SWIO. Since 2019, there have been efforts to create a regional network for coordinated response to stranding events as well as training and capacity building in the SWIO region. The present analysis represents a first investigation of stranding data collected by various members and collaborators within the IndoCet network, covering over 14,800km of coastline belonging to nine countries/territories. Between 2000–2020, there were 397 stranding events, representing 1,232 individual animals, 17 genera and 27 species, belonging to six families: four balaenopterids, one balaenid, one physeterid, two kogiids, six ziphiids and 14 delphinids. Seven mass strandings were recorded: two were composed of three to 20 individuals and five composed of > 20 individuals. Spatial analysis of stranding events indicated that local spatio-temporal clusters (excessive number of events in time and geographic space) were present in all countries/territories, except for the Comoros. The only significant cluster was detected on the southwest coast of Mauritius, just west of the village of Souillac. The SWIO region predominantly comprises relatively poor countries/territories, but imminent Ocean Economy developments are prevalent throughout the region. This study highlights the importance of establishing baselines upon which any future potential impact from anthropogenic developments in the region can be measured.Peer reviewe

Influence of Comorbidities on Therapeutic Progression of Diabetes Treatment in Australian Veterans: A Cohort Study

BACKGROUND: This study assessed whether the number of comorbid conditions unrelated to diabetes was associated with a delay in therapeutic progression of diabetes treatment in Australian veterans. METHODOLOGY/PRINCIPAL FINDINGS: A retrospective cohort study was undertaken using data from the Australian Department of Veterans' Affairs (DVA) claims database between July 2000 and June 2008. The study included new users of metformin or sulfonylurea medicines. The outcome was the time to addition or switch to another antidiabetic treatment. The total number of comorbid conditions unrelated to diabetes was identified using the pharmaceutical-based comorbidity index, Rx-Risk-V. Competing risk regression analyses were conducted, with adjustments for a number of covariates that included age, gender, residential status, use of endocrinology service, number of hospitalisation episodes and adherence to diabetes medicines. Overall, 20134 veterans were included in the study. At one year, 23.5% of patients with diabetes had a second medicine added or had switched to another medicine, with 41.4% progressing by 4 years. The number of unrelated comorbidities was significantly associated with the time to addition of an antidiabetic medicine or switch to insulin (subhazard ratio [SHR] 0.87 [95% CI 0.84–0.91], P<0.001). Depression, cancer, chronic obstructive pulmonary disease, dementia, and Parkinson's disease were individually associated with a decreased likelihood of therapeutic progression. Age, residential status, number of hospitalisations and adherence to anti-diabetic medicines delayed therapeutic progression. CONCLUSIONS / SIGNIFICANCE: Increasing numbers of unrelated conditions decreased the likelihood of therapeutic progression in veterans with diabetes. These results have implications for the development of quality measures, clinical guidelines and the construction of models of care for management of diabetes in elderly people with comorbidities.Agnes I. Vitry, Elizabeth E. Roughead, Adrian K. Preiss, Philip Ryan, Emmae N. Ramsay, Andrew L. Gilbert, Gillian E. Caughey, Sepehr Shakib, Adrian Esterman, Ying Zhang and Robyn A. McDermot

Muscle atrophy phenotype gene expression during spaceflight is linked to a metabolic crosstalk in both the liver and the muscle in mice

Human expansion in space is hampered by the physiological risks of spaceflight. The muscle and the liver are among the most affected tissues during spaceflight and their relationships in response to space exposure have never been studied. We compared the transcriptome response of liver and quadriceps from mice on NASA RR1 mission, after 37 days of exposure to spaceflight using GSEA, ORA, and sparse partial least square-differential analysis. We found that lipid metabolism is the most affected biological process between the two organs. A specific gene cluster expression pattern in the liver strongly correlated with glucose sparing and an energy-saving response affecting high energy demand process gene expression such as DNA repair, autophagy, and translation in the muscle. Our results show that impaired lipid metabolism gene expression in the liver and muscle atrophy gene expression are two paired events during spaceflight, for which dietary changes represent a possible countermeasure

Analgesic use, pain and daytime sedation in people with and without dementia in aged care facilities: a cross-sectional, multisite, epidemiological study protocol

INTRODUCTION: People living with dementia may experience and express pain in different ways to people without dementia. People with dementia are typically prescribed fewer analgesics than people without dementia indicating a potential difference in how pain is identified and treated in these populations. The objectives of this study are to (1) investigate the prevalence of analgesic load, pain and daytime sedation in people with and without dementia in Australian residential aged care facilities (RACFs), and (2) investigate the clinical and diagnostic associations between analgesic load, pain and daytime sedation in people with and without dementia in Australian RACFs. METHODS/ANALYSIS: This will be a cross-sectional study of 300 permanent residents of up to 10 low-level and high-level RACFs in South Australia with and without dementia. Trained study nurses will administer validated and dementia-specific assessments of self-reported and clinician-observed pain, sedation and other clinical and humanistic outcomes. Medicine-use data will be extracted directly from each resident's medication administration chart. Binary and multinominal logistic regression will be used to compute unadjusted and adjusted ORs and 95% CIs for factors associated with pain, analgesic load and daytime sedation. These factors will include dementia severity, behavioural and psychological symptoms, quality of life, resident satisfaction, attitudes towards medicines, activities of daily living and nutritional status. ETHICS AND DISSEMINATION: Institutional ethics approval has been granted. The findings will be disseminated through public lectures, professional and scientific conferences and in peer-reviewed journal articles. The findings of this study will allow for a better understanding of the prevalence and factors associated with analgesic use, pain and other outcomes in residential care. The findings of this study will be used to inform the development and implementation of strategies to improve the quality of life of people with dementia.Edwin C K Tan, Renuka Visvanathan, Sarah N Hilmer, Agnes I Vitry, Tara Quirke, Tina Emery, Leonie Robson, Terry Shortt, Simon Sheldrick, Sunny, Soon Won, Lee, Robyn Clothier, Emily Reeve, Danijela Gnjidic, Jenni Ilomäki, J Simon Bel

A self-controlled case series to assess the effectiveness of beta blockers for heart failure in reducing hospitalisations in the elderly

Background: To determine the suitability of using the self-controlled case series design to assess improvements in health outcomes using the effectiveness of beta blockers for heart failure in reducing hospitalisations as the example. Methods: The Australian Government Department of Veterans' Affairs administrative claims database was used to undertake a self-controlled case-series in elderly patients aged 65 years or over to compare the risk of a heart failure hospitalisation during periods of being exposed and unexposed to a beta blocker. Two studies, the first using a one year period and the second using a four year period were undertaken to determine if the estimates varied due to changes in severity of heart failure over time. Results: In the one year period, 3,450 patients and in the four year period, 12, 682 patients had at least one hospitalisation for heart failure. The one year period showed a non-significant decrease in hospitalisations for heart failure 4-8 months after starting beta-blockers, (RR, 0.76; 95% CI (0.57-1.02)) and a significant decrease in the 8-12 months post-initiation of a beta blocker for heart failure (RR, 0.62; 95% CI (0.39, 0.99)). For the four year study there was an increased risk of hospitalisation less than eight months post-initiation and significant but smaller decrease in the 8-12 month window (RR, 0.90; 95% CI (0.82, 0.98)). Conclusions: The results of the one year observation period are similar to those observed in randomised clinical trials indicating that the self-controlled case-series method can be successfully applied to assess health outcomes. However, the result appears sensitive to the study periods used and further research to understand the appropriate applications of this method in pharmacoepidemiology is still required. The results also illustrate the benefits of extending beta blocker utilisation to the older age group of heart failure patients in which their use is common but the evidence is sparse.Emmae N Ramsay, Elizabeth E Roughead, Ben Ewald, Nicole L Pratt and Philip Rya