Thiazide-Induced Hyponatremia Presenting as a Fall in an Older Adult.

Background: Regardless of age, first-line therapy for uncomplicated hypertension includes thiazide diuretics, long-acting calcium channel blockers, and renin-angiotensin system inhibitors. Even though older adults are often at increased risk of adverse drug events, specific guidelines for choosing between different classes of antihypertensives are lacking. Given the prevalence of hypertension in older adults, clinicians should be aware of the increased risk of electrolyte disorders after the initiation of thiazide diuretics in this population. Case Presentation: A patient aged > 90 years fell getting out of his bed 2 weeks following initiation of hydrochlorothiazide 25 mg daily medication therapy. Laboratory tests revealed a urine sodium of 35 mmol/L most consistent with hypovolemic hypoosmotic hyponatremia secondary to thiazide initiation. Hydrochlorothiazide was discontinued and sodium gradually normalized over the next 2 weeks without any other intervention. Conclusions: Despite being recommended as first-line therapy for uncomplicated hypertension, thiazide diuretics may cause more harm than good in older adults with risk factors for thiazide-induced hyponatremia, which should be considered before initiation.

Connecting the disconnected: Leveraging an in-home team member for video visits for older adults.

BACKGROUND: Older adults are interested and able to complete video visits, but often require coaching and practice to succeed. Data show a widening digital divide between older and younger adults using video visits. We conducted a qualitative feasibility study to investigate these gaps via ethnographic methods, including a team member in older participants' homes. METHODS: This ethnographic feasibility study included a virtual medication reconciliation visit with a clinical pharmacist for Veterans aged 65 and older taking 5 or more medications. An in-home study team member joined the participant and recorded observations in structured fieldnotes derived from the Updated Consolidated Framework for Implementation Research and Age-Friendly Health Systems. Fieldnotes included behind-the-scenes facilitators, barriers, and solutions to challenges before and during the visits. We conducted a thematic analysis of these observations and matched themes to implementation solutions from the Expert Recommendations for Implementing Change. RESULTS: Twenty participants completed a video visit. Participants were 74 years old (range 68-80) taking 12 daily medications (range 7-24). Challenges occurred in half of the visits and took the in-home team member and/or pharmacist an average of 10 minutes to troubleshoot. Challenges included notable new findings, such as that half of the participants required technology assistance for challenges that would not have been able to be solved by the pharmacist virtually. Furthermore, although many participants had a device or had used video visits before, some did not have a single device with video, audio, Internet, and access to their email username and password. CONCLUSIONS: Clinicians may apply these evidence-based implementation solutions to their approach to video visits with older adults, including having a team member join the visit before the clinician, involving tech-savvy family members, ensuring the device works with the visit platform ahead of time, and creating a troubleshooting guide from our common challenges.

Co-creating maps and atlasesRivals: How Scientists Learned to Cooperate Lorraine Daston Columbia Global Reports, 2023. 160 pp.

Cooperation was critical to the creation of two major scientific resources.

Impact of a vaccine passport on first-dose SARS-CoV-2 vaccine coverage by age and area-level social determinants of health in the Canadian provinces of Quebec and Ontario: an interrupted time series analysis.

BACKGROUND: In Canada, all provinces implemented vaccine passports in 2021 to reduce SARS-CoV-2 transmission in non-essential indoor spaces and increase vaccine uptake (policies active September 2021-March 2022 in Quebec and Ontario). We sought to evaluate the impact of vaccine passport policies on first-dose SARS-CoV-2 vaccination coverage by age, and area-level income and proportion of racialized residents. METHODS: We performed interrupted time series analyses using data from Quebec's and Ontario's vaccine registries linked to census information (population of 20.5 million people aged ≥ 12 yr; unit of analysis: dissemination area). We fit negative binomial regressions to first-dose vaccinations, using natural splines adjusting for baseline vaccination coverage (start: July 2021; end: October 2021 for Quebec, November 2021 for Ontario). We obtained counterfactual vaccination rates and coverage, and estimated the absolute and relative impacts of vaccine passports. RESULTS: In both provinces, first-dose vaccination coverage before the announcement of vaccine passports was 82% (age ≥ 12 yr). The announcement resulted in estimated increases in coverage of 0.9 percentage points (95% confidence interval [CI] 0.4-1.2) in Quebec and 0.7 percentage points (95% CI 0.5-0.8) in Ontario. This corresponds to 23% (95% CI 10%-36%) and 19% (95% CI 15%-22%) more vaccinations over 11 weeks. The impact was larger among people aged 12-39 years. Despite lower coverage in lower-income and more-racialized areas, there was little variability in the absolute impact by area-level income or proportion racialized in either province. INTERPRETATION: In the context of high vaccine coverage across 2 provinces, the announcement of vaccine passports had a small impact on first-dose coverage, with little impact on reducing economic and racial inequities in vaccine coverage. Findings suggest that other policies are needed to improve vaccination coverage among lower-income and racialized neighbourhoods and communities.

Medium-term scenarios of COVID-19 as a function of immune uncertainties and chronic disease.

As the SARS-CoV-2 trajectory continues, the longer-term immuno-epidemiology of COVID-19, the dynamics of Long COVID, and the impact of escape variants are important outstanding questions. We examine these remaining uncertainties with a simple modelling framework that accounts for multiple (antigenic) exposures via infection or vaccination. If immunity (to infection or Long COVID) accumulates rapidly with the valency of exposure, we find that infection levels and the burden of Long COVID are markedly reduced in the medium term. More pessimistic assumptions on host adaptive immune responses illustrate that the longer-term burden of COVID-19 may be elevated for years to come. However, we also find that these outcomes could be mitigated by the eventual introduction of a vaccine eliciting robust (i.e. durable, transmission-blocking and/or 'evolution-proof') immunity. Overall, our work stresses the wide range of future scenarios that still remain, the importance of collecting real-world epidemiological data to identify likely outcomes, and the crucial need for the development of a highly effective transmission-blocking, durable and broadly protective vaccine.

The role of mucosal barriers in disease progression and transmission.

Mucus is a biological hydrogel that coats and protects all non-keratinized wet epithelial surfaces. Mucins, the primary structural components of mucus, are critical components of the gel layer that protect against invading pathogens. For communicable diseases, pathogen-mucin interactions contribute to the pathogen's fate and the potential for disease progression in-host, as well as the potential for onward transmission. We begin by reviewing in-host mucus filtering mechanisms, including size filtering and interaction filtering, which regulate the permeability of mucus barriers to all molecules including pathogens. Next, we discuss the role of mucins in communicable diseases at the point of transmission (i.e. how the encapsulation of pathogens in emitted mucosal droplets externally to hosts may modulate pathogen infectivity and viability). Overall, mucosal barriers modulate both host susceptibility as well as the dynamics of population-level disease transmission. The study of mucins and their use in models and experimental systems are therefore crucial for understanding the mechanistic biophysical principles underlying disease transmission and the early stages of host infection.

Comparison of Physicochemical Properties of Native Mucus and Reconstituted Mucin Gels.

Simulating native mucus with model systems such as gels made from reconstituted mucin or commercially available polymers presents experimental advantages including greater sample availability and reduced inter- and intradonor heterogeneity. Understanding whether these gels reproduce the complex physical and biochemical properties of native mucus at multiple length scales is critical to building relevant experimental models, but few systematic comparisons have been reported. Here, we compared bulk mechanical properties, microstructure, and biochemical responses of mucus from different niches, reconstituted mucin gels (with similar pH and polymer concentrations as native tissues), and commonly used commercially available polymers. To evaluate gel properties across these length scales, we used small-amplitude oscillatory shear, single-particle tracking, and microaffinity chromatography with small analytes. With the exception of human saliva, the mechanical response of mucin gels was qualitatively similar to that of native mucus. The transport behavior of charged peptides through native mucus gels was qualitatively reproduced in gels composed of corresponding isolated mucins. Compared to native mucus, we observed substantial differences in the physicochemical properties of gels reconstituted from commercially available mucins and the substitute carboxymethylcellulose, which is currently used in artificial tear and saliva treatments. Our study highlights the importance of selecting a mucus model system guided by the length scale relevant to the scientific investigation or disease application.

Distributed medium viscosity yields quasi-exponential step-size probability distributions in heterogeneous media.

The analysis of the statistics of random walks undertaken by passive particles in complex media has important implications in a number of areas including pathogen transport and drug delivery. In several systems in which heterogeneity is important, the distribution of particle step-sizes has been found to be exponential in nature, as opposed to the Gaussian distribution associated with Brownian motion. Here, we first develop a theoretical framework to study a simplified version of this problem: the motion of passive tracers in a range of sub-environments with different viscosity. We show that in the limit of a large number of equi-distributed sub-environments spanning a broad viscosity range, an exact analytical expression for the underlying particle step-size distribution can be derived, which approaches an exponential distribution when step sizes are small. We then validate this using a simple experimental system of glycerol-water mixtures, in which the volume fraction of glycerol is systematically varied. Overall, the assumption of exponentially distributed step sizes may substantially over-estimate the incidence of large steps in heterogeneous systems, with important implications in the analysis of various biophysical processes.

One-year in: COVID-19 research at the international level in CORD-19 data.

The appearance of a novel coronavirus in late 2019 radically changed the community of researchers working on coronaviruses since the 2002 SARS epidemic. In 2020, coronavirus-related publications grew by 20 times over the previous two years, with 130,000 more researchers publishing on related topics. The United States, the United Kingdom and China led dozens of nations working on coronavirus prior to the pandemic, but leadership consolidated among these three nations in 2020, which collectively accounted for 50% of all papers, garnering well more than 60% of citations. China took an early lead on COVID-19 research, but dropped rapidly in production and international participation through the year. Europe showed an opposite pattern, beginning slowly in publications but growing in contributions during the year. The share of internationally collaborative publications dropped from pre-pandemic rates; single-authored publications grew. For all nations, including China, the number of publications about COVID track closely with the outbreak of COVID-19 cases. Lower-income nations participate very little in COVID-19 research in 2020. Topic maps of internationally collaborative work show the rise of patient care and public health clusters-two topics that were largely absent from coronavirus research in the two years prior to 2020. Findings are consistent with global science as a self-organizing system operating on a reputation-based dynamic.

Innovative vaccine approaches-a Keystone Symposia report.

The rapid development of COVID-19 vaccines was the result of decades of research to establish flexible vaccine platforms and understand pathogens with pandemic potential, as well as several novel changes to the vaccine discovery and development processes that partnered industry and governments. And while vaccines offer the potential to drastically improve global health, low-and-middle-income countries around the world often experience reduced access to vaccines and reduced vaccine efficacy. Addressing these issues will require novel vaccine approaches and platforms, deeper insight how vaccines mediate protection, and innovative trial designs and models. On June 28-30, 2021, experts in vaccine research, development, manufacturing, and deployment met virtually for the Keystone eSymposium "Innovative Vaccine Approaches" to discuss advances in vaccine research and development.

"If Their Face Starts Turning Purple, You Are Probably Doing Something Wrong": Young Men's Experiences with Choking During Sex.

Choking/strangulation during sex has become prevalent in the United States. Yet, no qualitative research has addressed men's choking experiences. Through interviews with 21 young adult men, we examined the language men use to refer to choking, how they first learned about it, their experiences with choking, and consent and safety practices. Men learned about choking during adolescence from pornography, partners, friends, and mainstream media. They engaged in choking to be kinky, adventurous, and to please partners. While many enjoyed or felt neutral about choking, others were reluctant to choke or be choked. Safety and verbal/non-verbal consent practices varied widely.

Deploying wearable sensors for pandemic mitigation: A counterfactual modelling study of Canada's second COVID-19 wave.

Wearable sensors can continuously and passively detect potential respiratory infections before or absent symptoms. However, the population-level impact of deploying these devices during pandemics is unclear. We built a compartmental model of Canada's second COVID-19 wave and simulated wearable sensor deployment scenarios, systematically varying detection algorithm accuracy, uptake, and adherence. With current detection algorithms and 4% uptake, we observed a 16% reduction in the second wave burden of infection; however, 22% of this reduction was attributed to incorrectly quarantining uninfected device users. Improving detection specificity and offering confirmatory rapid tests each minimized unnecessary quarantines and lab-based tests. With a sufficiently low false positive rate, increasing uptake and adherence became effective strategies for scaling averted infections. We concluded that wearable sensors capable of detecting presymptomatic or asymptomatic infections have potential to help reduce the burden of infection during a pandemic; in the case of COVID-19, technology improvements or supporting measures are required to keep social and resource costs sustainable.

Infectious disease in an era of global change.

The twenty-first century has witnessed a wave of severe infectious disease outbreaks, not least the COVID-19 pandemic, which has had a devastating impact on lives and livelihoods around the globe. The 2003 severe acute respiratory syndrome coronavirus outbreak, the 2009 swine flu pandemic, the 2012 Middle East respiratory syndrome coronavirus outbreak, the 2013-2016 Ebola virus disease epidemic in West Africa and the 2015 Zika virus disease epidemic all resulted in substantial morbidity and mortality while spreading across borders to infect people in multiple countries. At the same time, the past few decades have ushered in an unprecedented era of technological, demographic and climatic change: airline flights have doubled since 2000, since 2007 more people live in urban areas than rural areas, population numbers continue to climb and climate change presents an escalating threat to society. In this Review, we consider the extent to which these recent global changes have increased the risk of infectious disease outbreaks, even as improved sanitation and access to health care have resulted in considerable progress worldwide.

"It Was Scary, But Then It Was Kind of Exciting": Young Women's Experiences with Choking During Sex.

Choking/strangulation during sex is prevalent among young adults, with one study finding that 58% of women college students had ever been choked during sex. However, no qualitative study has examined women's experiences with choking/strangulation during sex outside of intimate partner violence. The purpose of our qualitative interview study was to investigate women's experiences with choking and/or being choked during partnered sex. Through in-depth interviews with 24 undergraduate and graduate women students ages 18 to 33, we sought to understand how women communicate about choking, their learning about and initiation into choking, their feelings about being choked and choking others, as well as consent and safety practices used in relation to choking. We found that women had first learned about choking through diverse sources including pornography, erotic stories, magazines, social media, friends, and partners. While all 24 women had been choked during sex, only 13 of 24 had ever choked a partner. They described having engaged in choking with men as well as women and with committed as well as more casual partner types. Participants described consensual and non-consensual choking experiences. While many women enjoyed choking, others did it largely to please their sexual partner. Women described different methods and intensities of having been choked. Although very few had ever sought out information on safety practices or risk reduction, and only some had established safe words or safe gestures with partners, participants consistently expressed a belief that the ways in which they and their partner(s) engaged in choking were safe.

Vaccine nationalism and the dynamics and control of SARS-CoV-2.

Vaccines provide powerful tools to mitigate the enormous public health and economic costs that the ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic continues to exert globally, yet vaccine distribution remains unequal among countries. To examine the potential epidemiological and evolutionary impacts of "vaccine nationalism," we extend previous models to include simple scenarios of stockpiling between two regions. In general, when vaccines are widely available and the immunity they confer is robust, sharing doses minimizes total cases across regions. A number of subtleties arise when the populations and transmission rates in each region differ, depending on evolutionary assumptions and vaccine availability. When the waning of natural immunity contributes most to evolutionary potential, sustained transmission in low-access regions results in an increased potential for antigenic evolution, which may result in the emergence of novel variants that affect epidemiological characteristics globally. Overall, our results stress the importance of rapid, equitable vaccine distribution for global control of the pandemic.

Epidemiological and evolutionary considerations of SARS-CoV-2 vaccine dosing regimes.

Given vaccine dose shortages and logistical challenges, various deployment strategies are being proposed to increase population immunity levels to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Two critical issues arise: How timing of delivery of the second dose will affect infection dynamics and how it will affect prospects for the evolution of viral immune escape via a buildup of partially immune individuals. Both hinge on the robustness of the immune response elicited by a single dose as compared with natural and two-dose immunity. Building on an existing immuno-epidemiological model, we find that in the short term, focusing on one dose generally decreases infections, but that longer-term outcomes depend on this relative immune robustness. We then explore three scenarios of selection and find that a one-dose policy may increase the potential for antigenic evolution under certain conditions of partial population immunity. We highlight the critical need to test viral loads and quantify immune responses after one vaccine dose and to ramp up vaccination efforts globally.

Topic evolution, disruption and resilience in early COVID-19 research.

The COVID-19 pandemic presented a challenge to the global research community as scientists rushed to find solutions to the devastating crisis. Drawing expectations from resilience theory, this paper explores how the trajectory of and research community around the coronavirus research was affected by the COVID-19 pandemic. Characterizing epistemic clusters and pathways of knowledge through extracting terms featured in articles in early COVID-19 research, combined with evolutionary pathways and statistical analysis, the results reveal that the pandemic disrupted existing lines of coronavirus research to a large degree. While some communities of coronavirus research are similar pre- and during COVID-19, topics themselves change significantly and there is less cohesion amongst early COVID-19 research compared to that before the pandemic. We find that some lines of research revert to basic research pursued almost a decade earlier, whilst others pursue brand new trajectories. The epidemiology topic is the most resilient among the many subjects related to COVID-19 research. Chinese researchers in particular appear to be driving more novel research approaches in the early months of the pandemic. The findings raise questions about whether shifts are advantageous for global scientific progress, and whether the research community will return to the original equilibrium or reorganize into a different knowledge configuration.