Collaborative Metabolism: Gut Microbes Play a Key Role in Canine and Feline Bile Acid Metabolism.

Bile acids, produced by the liver and secreted into the gastrointestinal tract, are dynamic molecules capable of impacting the overall health of dogs and cats in many contexts. Importantly, the gut microbiota metabolizes host primary bile acids into chemically distinct secondary bile acids. This review explores the emergence of new literature connecting microbial-derived bile acid metabolism to canine and feline health and disease. Moreover, this review highlights multi-omic methodologies for translational research as an area for continued growth in veterinary medicine aimed at accelerating microbiome science and medicine as it pertains to bile acid metabolism in dogs and cats.

The Forgotten Middle: Worsening Health And Economic Trends Extend To Americans With Modest Resources Nearing Retirement.

In an aging US society, anticipating the challenges that future seniors will face is essential. This study analyzed the health and economic well-being of five cohorts of Americans in their mid-fifties between 1994 and 2018 using the Future Elderly Model, a dynamic microsimulation based on the Health and Retirement Study. We projected mortality, quality-adjusted life years, health expenditures, and income and benefits. We classified individuals by economic status and focused on the lower middle and upper middle of the economic distribution. Outcome disparities between people in these two groups widened substantially between the 1994 and 2018 cohorts. Quality-adjusted life expectancy increased (5 percent) for the upper-middle economic status group but stagnated for their lower-middle peers. We found that the combined value of the current stock (financial and housing wealth) and the present value of the expected flow of resources (income, health expenditures, and quality-adjusted life-years) after age sixty grew 13 percent for the upper-middle group between cohorts, whereas people in the lower-middle group in 2018 were left scarcely better off (3 percent growth) than their peers two decades earlier. The relatively neglected "forgotten middle" group of near-retirees in the lower-middle group may require stronger supports than are currently available to them.

Societal Adaptation to Aging and Prevalence of Depression Among Older Adults: Evidence From 20 Countries.

Policy Points Countries have adopted different strategies to support aging populations, which are broadly reflected in social, economic, and contextual environments. Referred to as "societal adaptation to aging," these factors affect countries' capacity to support older adults. Results from our study show that countries with more robust societal adaptation to aging had lower depression prevalence. Reductions in depression prevalence occurred among every investigated sociodemographic group and were most pronounced among the old-old. Findings suggest that societal factors have an underacknowledged role in shaping depression risk. Policies that improve societal approaches to aging may reduce depression prevalence among older adults. CONTEXT: Countries have adopted various formal and informal approaches to support older adults, which are broadly reflected in different policies, programs, and social environments. These contextual environments, broadly referred to as "societal adaptation to aging," may affect population health. METHODS: We used a new theory-based measure that captured societal adaptation to aging, the Aging Society Index (ASI), which we linked with harmonized individual-level data from 89,111 older adults from 20 countries. Using multi-levels models that accounted for differences in the population composition across countries, we estimated the association between country-level ASI scores and depression prevalence. We also tested if associations were stronger among the old-old and among sociodemographic groups that experience more disadvantage (i.e., women, those with lower educational attainment, unmarried adults). FINDINGS: We found that countries with higher ASI scores, indicating more comprehensive approaches to supporting older adults, had lower depression prevalence. We found especially strong reductions in depression prevalence among the oldest adults in our sample. However, we did not find stronger reductions among sociodemographic groups who may experience more disadvantage. CONCLUSIONS: Country-level strategies to support older adults may affect depression prevalence. Such strategies may become increasingly important as adults grow older. These results offer promising evidence that improvements in societal adaptation to aging-such as through adoption of more comprehensive policies and programs targeting older adults-may be one avenue to improve population mental health. Future research could investigate observed associations using longitudinal and quasi-experimental study designs, offering additional information regarding a potential causal relationship.

Meaningful patient and public involvement in digital health innovation, implementation and evaluation: A systematic review.

INTRODUCTION: The importance of meaningfully involving patients and the public in digital health innovation is widely acknowledged, but often poorly understood. This review, therefore, sought to explore how patients and the public are involved in digital health innovation and to identify factors that support and inhibit meaningful patient and public involvement (PPI) in digital health innovation, implementation and evaluation. METHODS: Searches were undertaken from 2010 to July 2020 in the electronic databases MEDLINE, EMBASE, PsycINFO, CINAHL, Scopus and ACM Digital Library. Grey literature searches were also undertaken using the Patient Experience Library database and Google Scholar. RESULTS: Of the 10,540 articles identified, 433 were included. The majority of included articles were published in the United States, United Kingdom, Canada and Australia, with representation from 42 countries highlighting the international relevance of PPI in digital health. 112 topic areas where PPI had reportedly taken place were identified. Areas most often described included cancer (n = 50), mental health (n = 43), diabetes (n = 26) and long-term conditions (n = 19). Interestingly, over 133 terms were used to describe PPI; few were explicitly defined. Patients were often most involved in the final, passive stages of an innovation journey, for example, usability testing, where the ability to proactively influence change was severely limited. Common barriers to achieving meaningful PPI included data privacy and security concerns, not involving patients early enough and lack of trust. Suggested enablers were often designed to counteract such challenges. CONCLUSIONS: PPI is largely viewed as valuable and essential in digital health innovation, but rarely practised. Several barriers exist for both innovators and patients, which currently limits the quality, frequency and duration of PPI in digital health innovation, although improvements have been made in the past decade. Some reported barriers and enablers such as the importance of data privacy and security appear to be unique to PPI in digital innovation. Greater efforts should be made to support innovators and patients to become meaningfully involved in digital health innovations from the outset, given its reported benefits and impacts. Stakeholder consensus on the principles that underpin meaningful PPI in digital health innovation would be helpful in providing evidence-based guidance on how to achieve this. PATIENT OR PUBLIC CONTRIBUTION: This review has received extensive patient and public contributions with a representative from the Patient Experience Library involved throughout the review's conception, from design (including suggested revisions to the search strategy) through to article production and dissemination. Other areas of patient and public contributor involvement include contributing to the inductive thematic analysis process, refining the thematic framework and finalizing theme wording, helping to ensure relevance, value and meaning from a patient perspective. Findings from this review have also been presented to a variety of stakeholders including patients, patient advocates and clinicians through a series of focus groups and webinars. Given their extensive involvement, the representative from the Patient Experience Library is rightly included as an author of this review.

Thermal ecology of Northern Water Snakes (Nerodia sipedon) in a northern wetland in central Michigan.

Semi-aquatic north-temperate reptiles experience challenging environmental conditions for thermoregulation on both seasonal and daily bases. We studied the thermal biology of north-temperate Northern Water Snakes (Nerodia sipedon) in central Michigan by remote radiotelemetry monitoring of snake body temperature (Tb) using surgically implanted thermally-sensitive radio-transmitters and by measuring operative temperatures (Te) across a range of microhabitats using biophysical models. Our goals included evaluation of thermoregulatory capabilities at a locality that we viewed to be a fine-grained thermal environment, seasonal variations in patterns of thermoregulation, and the effects of sex on thermoregulation. During summer, snakes showed diel Tb cycling apparently using the open Sphagnum mat for late morning warming and shuttling among different microhabitats until early evening when a monotonic decline in Tb ensued and continued through the early morning hours. Snakes attained Tb within their laboratory-determined preferred body temperature range (Tset = 28-33 °C) mostly during late afternoon and with average percentages of Tb values for individual snakes within Tset range when permitted by operative temperatures (Ex) between 68 and 70% of the time depending on method of measurement. Relatively high investment in thermoregulation when thermal conditions were poor occurred only during September but declined thereafter as snakes prepared to overwinter. We did not detect differences in thermoregulation among reproductive females, non-reproductive females, and males. Relative to a population of N. sipedon at a higher latitude in Ontario our snakes showed a relatively high Tset range and thermoregulated more effectively, particularly during the daylight hours. It remains unclear how much inter-population variation in thermoregulation is due to potential adaptations to latitude, to habitat differences, or variations in methodologies.

Use and usability of GP online services: a mixed-methods sequential study, before and during the COVID-19 pandemic, based on qualitative interviews, analysis of routine eConsult usage and feedback data, and assessment of GP websites in Devon and Cornwall, England.

OBJECTIVES: We explored use and usability of general practitioner (GP) online services. SETTING: Devon and Cornwall, England. DESIGN: Mixed-methods sequential study based on qualitative interviews, analysis of routine eConsult usage and feedback data, and assessment of GP websites. METHODS: First, we interviewed 32 staff and 18 patients from seven practices in June 2018. Second, we used routinely collected consultation meta-data and, third, patient feedback data for all practices using eConsult from June 2018 to March 2021. Lastly, we examined GP websites' usability in January 2020 and September 2021. RESULTS: Interviews suggested practices infrequently involved patients in eConsult implementation. Some patients 'gamed' the system to achieve what they wanted. Usage data showed a major increase in eConsult resulting from COVID-19. Women used eConsult twice as much as men. Older had similar eConsult consultation rates to younger patients. Patient feedback forms were completed for fewer than 3% of consultations. Patients were mostly satisfied with eConsult but some had concerns about its length and repetitiveness, lack of continuity over time and between eConsult and medical records. We did not find clear evidence that patients' suggested improvements were acted on. Finally, few GP websites met accessibility guidelines and may hinder access to online national services such as eConsult. CONCLUSION: Given that, face to face, older people consult more, usage data suggest that older people have reduced online access. That the female-to-male ratio of eConsult use use was even greater than 'traditional' face-to-face ratio was unexpected and needs further research. Although eConsult collects and uses routine patient feedback to improve the system, more open systems for patient feedback, such as Care Opinion, may be more effective in helping online systems evolve. Lastly, we question the need for GP websites and suggest that national or regional services are better placed to maintain accessible services.

A US State Index of Successful Aging: Differences Between States and Over Time.

Policy Points The focus of successful aging is on the social contexts that enable individuals to be productively engaged and secure, with an emphasis on equity. There is currently no index to measure progress towards this goal at the US state level. We developed an empirical index for the evaluation of US state adaptation to societal aging across five critical domains that support successful population aging: (1) productivity and engagement, (2) security, (3) equity, (4) cohesion, and (5) well-being. Our index shows substantial variability over time and is not overly influenced by the performance of an individual domain. This suggests that it can be used to monitor state progress over time toward the goal of supporting successful aging. Rather than a major national trend, there are large between-state differences and changes in our index over time. This suggests individual US state policies and programs, as well as local economic conditions, may have a substantial impact on adaptations to societal aging. CONTEXT: Although it is recognized that aspects of US state environments impact the likelihood that older adults age successfully, there is currently no reliable and comprehensive measure of contexts that best support successful aging at a state level. The current project adapts a multidimensional index previously used to assess adaptation to successful aging in developed countries and applies it to the 50 US states and the District of Columbia. METHODS: We obtained data from multiple sources for all 50 US states and the District of Columbia from 2003 to 2017 in order to measure five distinct domains that define successful population aging: (1) productivity and engagement, (2) security, (3) equity, (4) cohesion, and (5) well-being. We created a ranking of states for the year 2017 based on these domains, and also examined how individual US state rankings changed over time from 2003 to 2017. FINDINGS: The level of adaptation to successful aging varied substantially between states and over time. The highest-ranked states in 2017 were Vermont, Hawaii, Iowa, Colorado, and New Hampshire, and the lowest-ranked states were Louisiana, Arkansas, Kentucky, West Virginia, and Mississippi. Mississippi, South Carolina, Iowa, Arizona, and Delaware had the greatest improvement in their ranking over the period of 2003 to 2017. Our findings were generally robust to the weighting scheme used and were not overly influenced by any particular domain. CONCLUSIONS: The US State Index of Successful Aging can be used to monitor US state progress in promoting the well-being and health of aging populations. Factors driving the changes in the index remain to be elucidated.

Rapid systematic review of respiratory rate as a vital sign of clinical deterioration in COVID-19.

OBJECTIVES: This meta-analysis aimed to establish a clinical evidence base for respiratory rate (RR) as a single predictor of early-onset COVID-19. The review also looked to determine the practical implementation of mobile respiratory rate measuring devices where information was available. METHODS: We focused on domestic settings with older adults. Relevant studies were identified through MEDLINE, Embase, and CENTRAL databases. A snowballing method was also used. Articles published from the beginning of the COVID-19 pandemic (2019) until Feb 2022 were selected. Databases were searched for terms related to COVID-19 and respiratory rate measurements in domestic patients. RESULTS: A total of 2,889 articles were screened for relevant content, of which 60 full-text publications were included. We compared the Odds Ratios and statistically significant results of both vital signs. CONCLUSION: Multinational studies across dozens of countries have shown respiratory rate to have predictive accuracy in detecting COVID-19 deterioration. However, considerable variability is present in the data, making it harder to be sure about the effects. There is no meaningful difference in data quality in terms of variability (95% CI intervals) between vital signs as predictors of decline in COVID-19 patients. Contextual and economic factors will likely determine the choice of measurement used.

Reimbursement for genetic variant reinterpretation: five questions payers should ask.

Reaching the goals set by the Health Care Payment and Learning Action Network requires an unyielding and unrelenting focus on encouraging providers to adopt advanced alternative payment models (APMs). Many of these models will continue to be voluntary because they either are in early stages or have not yet proven their effectiveness. The models that have proven their effectiveness should become permanent, comprising the new way that providers are paid in the Medicare program. Either way, getting today's high performers into those programs and keeping them engaged to continue to innovate and set new benchmarks is as important as attracting and improving the performance of poorer performers. That will require a shift in Medicare's policy on pricing and evaluating APMs.

Application of machine learning to large in vitro databases to identify drug-cancer cell interactions: azithromycin and KLK6 mutation status.

Recent advances in machine learning promise to yield novel insights by interrogation of large datasets ranging from gene expression and mutation data to CRISPR knockouts and drug screens. We combined existing and new algorithms with available experimental data to identify potentially clinically relevant relationships to provide a proof of principle for the promise of machine learning in oncological drug discovery. Specifically, we screened cell line data from the Cancer Dependency Map for the effects of azithromycin, which has been shown to kill cancer cells in vitro. Our findings demonstrate a strong relationship between Kallikrein Related Peptidase 6 (KLK6) mutation status and the ability of azithromycin to kill cancer cells in vitro. While the application of azithromycin showed no meaningful average effect in KLK6 wild-type cell lines, statistically significant enhancements of cell death are seen in multiple independent KLK6-mutated cancer cell lines. These findings suggest a potentially valuable clinical strategy in patients with KLK6-mutated malignancies.

Interobserver reliability of canine urine specific gravity assessed by analog or digital refractometers.

Refractometry is utilized routinely to evaluate canine urine specific gravity (USG) in veterinary clinical settings. We aimed to determine if the magnitude of interobserver reliability when assessing canine USG via refractometry could impact clinical judgment. USG was determined in 38 dogs by 3 registered veterinary technicians (RVTs) using both an optical analog refractometer and a digital refractometer. Summary statistics were reported, interobserver reliability was assessed via intraclass correlation coefficient (ICC) analysis through a 2-way mixed-effects model, and agreement between RVT pairs was compared through Bland-Altman plots. The median analog refractometer USG measurement was 1.018 (range: 1.004-1.040) and for the digital refractometer was 1.0176 (1.0035-1.0357). The analog refractometer average measure ICC was 0.995 (95% CI: 0.992, 0.997; p < 0.001). The digital refractometer average measure ICC was 0.999 (95% CI: 0.999, 1.000; p < 0.001). Strong agreement between all pairs of RVTs was seen via Bland-Altman plots for both analog and digital refractometers, with 95% CIs spanning no more than 0.002 in either the positive or negative direction for all pairings. The interobserver variability in canine USG measurements by RVTs was trivial and did not impact clinical judgment and decision-making.

GP trainee responses to using SHERPA for multimorbidity consultations.

UK general practitioner (GP) trainees are taught a consultation model which elicits the patients' main reason for consulting 'today'. This approach will often miss important issues for the increasing number of patients with multimorbidity. We developed the SHERPA model as a person-centred biopsychosocial framework for consulting patients with multimorbidity to address this. We aimed to examine GPs trainees' responses to SHERPA when integrated into their vocational training. The research design was qualitative and participants were GPs trainees in vocational training from one UK training location. GP trainees were introduced to the SHERPA model through interactive workshops. Qualitative data were collected from 16 participants, through four hours of teaching observation, 24 feedback templates, six practical applications of SHERPA and eight one-to-one interviews. Data were transcribed, and, using the Framework approach, systematically analysed, focussing on trainees' learning and application of the model. The results demonstrated that all participants engaged well with the teaching sessions, brought observations from their own experience, and reflected on particularly complex consultations. Half of the participants applied SHERPA successfully with their patients, particularly repeat attenders. Barriers to this approach were: selecting appropriate patients; perceived time pressure; lack of familiarity using the model; viewing SHERPA as 'additional', rather than integral, to shared decision-making in complex situations. The SHERPA model was viewed as helpful by these GP trainees for patients with whom they had established a relationship. Earlier introduction and regular support from trainers, where trainees reflect on experience of SHERPA, could increase confidence in using this method.

Rethinking the urban physical environment for century-long lives: from age-friendly to longevity-ready cities.

In response to increasing life expectancies and urbanization, initiatives for age-friendly cities seek to facilitate active and healthy aging by strengthening supports and services for older people. While laudable, these efforts typically neglect early-life exposures that influence long-term well-being. With a focus on the urban physical environment, we argue that longevity-ready cities can accomplish more than initiatives focused solely on old age. We review features of cities that cumulatively influence healthy aging and longevity, discuss the need for proactive interventions in a changing climate, and highlight inequities in the ambient physical environment, especially those encountered at early ages, that powerfully contribute to disparities in later life stages. Compared with strategies aimed largely at accommodating older populations, longevity-ready cities would aim to reduce the sources of disadvantages across the life course and simultaneously improve the well-being of older people.

Gender differences in countries' adaptation to societal ageing: an international cross-sectional comparison.

BACKGROUND: Gender differences in life expectancy and societal roles have implications for a country's capacity to support its older population. Specifically, the longevity risk associated with longer life expectancy of women, with greater risk of morbidity entails different needs between genders in older age. We aimed to quantify gender differences in the ageing experience of older people in Organization for Economic Cooperation and Development (OECD) countries as a first step in identifying policy gaps and differences in the allocation of resources and social support for older men and women. METHODS: We constructed a multidimensional Ageing Index to account for gender differences in societal ageing, using mostly gender-disaggregated latest available data between 2015 and 2019, for 18 OECD countries. Our Ageing Index is a weighted sum of scores for five domains, which consisted of various measures, that are important for societal ageing: wellbeing, productivity and engagement, equity, security, and cohesion. The construction of the domains and their relative weighting was determined by the Research Network on an Ageing Society, an interdisciplinary group of academics. We computed the overall index and domain scores (from 0 to 100) for each gender and compared these scores between genders and countries. FINDINGS: In every country, gender differences in key domains of societal ageing favour men. Countries in northern Europe (ie, Denmark, Sweden, Finland and Norway), the Netherlands, and Japan had high overall Index scores for both genders, whereas many eastern and southern European countries (eg, Hungary, Poland, and Slovenia) performed less well. Countries with the largest gender difference in Index scores include the Netherlands, Germany, and Italy, whereas Ireland, Spain, and Poland had the smallest difference. Gender differences were present for the domains of productivity and engagement, security, and cohesion. Gender differences favoured men for domain productivity and engagement (mean 10·2, 95% CI 7·8-12·6; p<0·0001), security (10·3, 7·8-12·7; p<0·0001), and cohesion (21·1, 13·9-28·1; p<0·0001). Although the domains of wellbeing and equity showed more mixed results, they nonetheless showed a slight advantage for men. INTERPRETATION: Our multidimensional index helps to identify specific gender differences along key domains of societal ageing in various OECD countries. Furthermore, the inter-country comparisons reveal those countries with more successful societal ageing, which could be instructive for policy makers. FUNDING: John A Hartford Foundation and the Singapore Ministry of Education.