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

Comorbid chronic diseases, discordant impact on mortality in older people: a 14-year longitudinal population study

Objectives: To determine the impact of comorbid chronic diseases on mortality in older people. Design: Prospective cohort study (1992e2006). Associations between numbers of chronic diseases or mutually exclusive comorbid chronic diseases on mortality over 14 years, by Cox proportional hazards model adjusting for sociodemographic variables or KaplaneMeier analyses, respectively. Setting: Population based, Australia. Participants: 2087 randomly selected participants aged $65 years old, living in the community or institutions. Main results: Participants with 3e4 or$5 diseases had a 25% (95% CI 1.05 to 1.5, p¼0.01) and 80% (95% CI 1.5 to 2.2, p<0.0001) increased risk of mortality, respectively, by comparison with no chronic disease, after adjusting for age, sex and residential status. When cardiovascular disease (CVD), mental health problem or diabetes were comorbid with arthritis, there was a trend towards increased survival (range 8.2e9.5 years) by comparison with CVD, mental health problem or diabetes alone (survival 5.8e6.9 years). This increase in survival with arthritis as a comorbidity was negated when CVD and mental health problems or CVD and diabetes were present in disease combinations together. Conclusion: Older people with $3 chronic diseases have increased risk of mortality, but discordant effects on survival depend on specific disease combinations. These results raise the hypothesis that patients who have an increased likelihood of opportunity for care from their physician are more likely to have comorbid diseases detected and managed.G E Caughey, E N Ramsay, A I Vitry, A L Gilbert, M A Luszcz, P Ryan and E E Roughea

Information from pharmaceutical companies and the quality, quantity, and cost of physicians' prescribing: a systematic review

BACKGROUND: Pharmaceutical companies spent $57.5 billion on pharmaceutical promotion in the United States in 2004. The industry claims that promotion provides scientific and educational information to physicians. While some evidence indicates that promotion may adversely influence prescribing, physicians hold a wide range of views about pharmaceutical promotion. The objective of this review is to examine the relationship between exposure to information from pharmaceutical companies and the quality, quantity, and cost of physicians' prescribing. METHODS AND FINDINGS: We searched for studies of physicians with prescribing rights who were exposed to information from pharmaceutical companies (promotional or otherwise). Exposures included pharmaceutical sales representative visits, journal advertisements, attendance at pharmaceutical sponsored meetings, mailed information, prescribing software, and participation in sponsored clinical trials. The outcomes measured were quality, quantity, and cost of physicians' prescribing. We searched Medline (1966 to February 2008), International Pharmaceutical Abstracts (1970 to February 2008), Embase (1997 to February 2008), Current Contents (2001 to 2008), and Central (The Cochrane Library Issue 3, 2007) using the search terms developed with an expert librarian. Additionally, we reviewed reference lists and contacted experts and pharmaceutical companies for information. Randomized and observational studies evaluating information from pharmaceutical companies and measures of physicians' prescribing were independently appraised for methodological quality by two authors. Studies were excluded where insufficient study information precluded appraisal. The full text of 255 articles was retrieved from electronic databases (7,185 studies) and other sources (138 studies). Articles were then excluded because they did not fulfil inclusion criteria (179) or quality appraisal criteria (18), leaving 58 included studies with 87 distinct analyses. Data were extracted independently by two authors and a narrative synthesis performed following the MOOSE guidelines. Of the set of studies examining prescribing quality outcomes, five found associations between exposure to pharmaceutical company information and lower quality prescribing, four did not detect an association, and one found associations with lower and higher quality prescribing. 38 included studies found associations between exposure and higher frequency of prescribing and 13 did not detect an association. Five included studies found evidence for association with higher costs, four found no association, and one found an association with lower costs. The narrative synthesis finding of variable results was supported by a meta-analysis of studies of prescribing frequency that found significant heterogeneity. The observational nature of most included studies is the main limitation of this review. CONCLUSIONS: With rare exceptions, studies of exposure to information provided directly by pharmaceutical companies have found associations with higher prescribing frequency, higher costs, or lower prescribing quality or have not found significant associations. We did not find evidence of net improvements in prescribing, but the available literature does not exclude the possibility that prescribing may sometimes be improved. Still, we recommend that practitioners follow the precautionary principle and thus avoid exposure to information from pharmaceutical companies.Geoffrey K. Spurling, Peter R. Mansfield, Brett D. Montgomery, Joel Lexchin, Jenny Doust, Noordin Othman and Agnes I. Vitr

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

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

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

Out of Their Depth? Isolated Deep Populations of the Cosmopolitan Coral Desmophyllum dianthus May Be Highly Vulnerable to Environmental Change

Deep sea scleractinian corals will be particularly vulnerable to the effects of climate change, facing loss of up to 70% of their habitat as the Aragonite Saturation Horizon (below which corals are unable to form calcium carbonate skeletons) rises. Persistence of deep sea scleractinian corals will therefore rely on the ability of larvae to disperse to, and colonise, suitable shallow-water habitat. We used DNA sequence data of the internal transcribed spacer (ITS), the mitochondrial ribosomal subunit (16S) and mitochondrial control region (MtC) to determine levels of gene flow both within and among populations of the deep sea coral Desmophyllum dianthus in SE Australia, New Zealand and Chile to assess the ability of corals to disperse into different regions and habitats. We found significant genetic subdivision among the three widely separated geographic regions consistent with isolation and limited contemporary gene flow. Furthermore, corals from different depth strata (shallow <600 m, mid 1000–1500 m, deep >1500 m) even on the same or nearby seamounts were strongly differentiated, indicating limited vertical larval dispersal. Genetic differentiation with depth is consistent with the stratification of the Subantarctic Mode Water, Antarctic Intermediate Water, the Circumpolar Deep and North Pacific Deep Waters in the Southern Ocean, and we propose that coral larvae will be retained within, and rarely migrate among, these water masses. The apparent absence of vertical larval dispersal suggests deep populations of D. dianthus are unlikely to colonise shallow water as the aragonite saturation horizon rises and deep waters become uninhabitable. Similarly, assumptions that deep populations will act as refuges for shallow populations that are impacted by activities such as fishing or mining are also unlikely to hold true. Clearly future environmental management strategies must consider both regional and depth-related isolation of deep-sea coral populations

Differential Effects of Comorbidity on Antihypertensive and Glucose-Regulating Treatment in Diabetes Mellitus – A Cohort Study

BACKGROUND: Comorbidity is often mentioned as interfering with "optimal" treatment decisions in diabetes care. It is suggested that diabetes- related comorbidity will increase adequate treatment, whereas diabetes- unrelated comorbidity may decrease this process of care. We hypothesized that these effects differ according to expected priority of the conditions. METHODS: We evaluated the relationship between comorbidity and treatment intensification in a study of 11,248 type 2 diabetes patients using the GIANTT (Groningen Initiative to Analyse type 2 diabetes Treatment) database. We formed a cohort of patients with a systolic blood pressure >/= 140 mmHg (6,820 hypertensive diabetics), and a cohort of patients with an HbA1c >/= 7% (3,589 hyperglycemic diabetics) in 2007. We differentiated comorbidity by diabetes-related or unrelated conditions and by priority. High priority conditions include conditions that are life- interfering, incident or requiring new medication treatment. We performed Cox regression analyses to assess association with treatment intensification, defined as dose increase, start, or addition of drugs. RESULTS: In both the hypertensive and hyperglycemic cohort, only patients with incident diabetes-related comorbidity had a higher chance of treatment intensification (HR 4.48, 2.33-8.62 (p<0.001) for hypertensives; HR 2.37, 1.09-5.17 (p = 0.030) for hyperglycemics). Intensification of hypertension treatment was less likely when a new glucose-regulating drug was prescribed (HR 0.24, 0.06-0.97 (p = 0.046)). None of the prevalent or unrelated comorbidity was significantly associated with treatment intensification. CONCLUSIONS: Diabetes-related comorbidity induced better risk factor treatment only for incident cases, implying that appropriate care is provided more often when complications occur. Diabetes- unrelated comorbidity did not affect hypertension or hyperglycemia management, even when it was incident or life-interfering. Thus, the observed "undertreatment" in diabetes care cannot be explained by constraints caused by such comorbidity

Mechanically assisted electrochemical degradation of alumina-TiC composites

Alumina-TiC composite material is a tough ceramic composite with excellent hardness, wear resistance and oxidation resistance in dry and high-temperature conditions. In aqueous conditions, however, it is likely to be electrochemically active facilitating charge transfer processes due to the conductive nature of TiC. For application as an orthopedic biomaterial, it is crucial to assess the electrochemical behavior of this composite, especially under a combined mechanical and electrochemical environment. In this study, we examined the mechanically assisted electrochemical performance of alumina-TiC composite in an aqueous environment. The spontaneous electrochemical response to brushing abrasion was measured. Changes in the magnitude of electrochemical current with abrasion test conditions and possible causal relationship to the alteration in surface morphology were examined. Results showed that the alumina matrix underwent abrasive wear with evidence of microploughing and grain boundary damage. Chemical analysis revealed TiO2 formation in the abraded region, indicating oxidation of the conductive TiC domain. Furthermore, wear debris from alumina abrasion appeared to affect reaction kinetics at the composite-electrolyte interface. From this work, we established that the composite undergoes abrasion assisted electrochemical degradation even in gentle abrasive conditions and the severity of degradation is related to temperature and conditions of test environment