Nature and human well-being: The olfactory pathway.

The world is undergoing massive atmospheric and ecological change, driving unprecedented challenges to human well-being. Olfaction is a key sensory system through which these impacts occur. The sense of smell influences quality of and satisfaction with life, emotion, emotion regulation, cognitive function, social interactions, dietary choices, stress, and depressive symptoms. Exposures via the olfactory pathway can also lead to (anti-)inflammatory outcomes. Increased understanding is needed regarding the ways in which odorants generated by nature (i.e., natural olfactory environments) affect human well-being. With perspectives from a range of health, social, and natural sciences, we provide an overview of this unique sensory system, four consensus statements regarding olfaction and the environment, and a conceptual framework that integrates the olfactory pathway into an understanding of the effects of natural environments on human well-being. We then discuss how this framework can contribute to better accounting of the impacts of policy and land-use decision-making on natural olfactory environments and, in turn, on planetary health.

Accessibility of Pulmonary Rehabilitation in the US.

This cross-sectional study examines nationwide travel time to pulmonary rehabilitation (PR) programs and PR access in the US.

Differential cardiopulmonary haemodynamic phenotypes in PASC-related exercise intolerance.

Background: Post-acute sequelae of COVID-19 (PASC) affect a significant proportion of patients who have previously contracted SARS-CoV-2, with exertional intolerance being a prominent symptom. This study aimed to characterise the invasive haemodynamic abnormalities of PASC-related exertional intolerance using invasive cardiopulmonary exercise testing (iCPET). Study design and intervention: 55 patients were recruited from the Yale Post-COVID-19 Recovery Program, with most experiencing mild acute illness. Supine right heart catheterisation and iCPET were performed on all participants. Main results: The majority (75%) of PASC patients exhibited impaired peak systemic oxygen extraction (pEO2) during iCPET in conjunction with supranormal cardiac output (CO) (i.e., PASC alone group). On average, the PASC alone group exhibited a "normal" peak exercise capacity, V'O2 (89±18% predicted). ∼25% of patients had evidence of central cardiopulmonary pathology (i.e., 12 with resting and exercise heart failure with preserved ejection fraction (HFpEF) and two with exercise pulmonary hypertension (PH)). PASC patients with HFpEF (i.e., PASC HFpEF group) exhibited similarly impaired pEO2 with well compensated PH (i.e., peak V'O2 and CO >80% respectively) despite aberrant central cardiopulmonary exercise haemodynamics. PASC patients with HFpEF also exhibited increased body mass index of 39±7 kg·m-2. To examine the relative contribution of obesity to exertional impairment in PASC HFpEF, a control group comprising obese non-PASC group (n=61) derived from a historical iCPET cohort was used. The non-PASC obese patients with preserved peak V'O2 (>80% predicted) exhibited a normal peak pulmonary artery wedge pressure (17±14 versus 25±6 mmHg; p=0.03) with similar maximal voluntary ventilation (90±12 versus 86±10% predicted; p=0.53) compared to PASC HFpEF patients. Impaired pEO2 was not significantly different between PASC patients who underwent supervised rehabilitation and those who did not (p=0.19). Conclusions: This study highlights the importance of considering impaired pEO2 in PASC patients with persistent exertional intolerance unexplained by conventional investigative testing. Results of the current study also highlight the prevalence of a distinct high output HFpEF phenotype in PASC with a primary peripheral limitation to exercise.

Acute and subacute neurovascular impact of cryptogenic air emboli.

Background: Cerebral air embolism is a rare cause of acute ischemic stroke that is becoming increasingly well-described in the literature. However, the mechanism and severity of this type of injury can vary, with ischemia typically emerging early in the course of care. To the best of our knowledge, delayed ischemia in this setting has not yet been described. Case Description: A stroke code was called for an unresponsive, hospitalized, 75-year-old man. A computerized tomography (CT) scan of the head revealed air within the right greater than left hemispheric cortical veins with loss of sulcation, concerning for developing ischemia, and CT angiography revealed absent opacification of the distal cortical vessels in the right anterior cerebral artery and middle cerebral artery territories. Magnetic resonance imaging (MRI) of the brain was obtained 5.75 h after the patient's last known well-showed small areas of subtle cortical diffusion restriction. Follow-up CT head within 24 h showed near-complete resolution of the air emboli after treatment with 100% fraction of inspired oxygen on mechanical ventilation. Subsequent MRI, performed 4 days after the initial event, showed extensive cortical diffusion restriction and cerebral edema crossing vascular territories. Conclusion: This case highlights that cerebral air emboli can cause delayed ischemia that may not be appreciated on initial imaging. As such, affected patients may require intensive neurocritical care management, close neurologic monitoring, and repeat imaging irrespective of initial radiographic findings.

Availability and Accessibility of Live Nonreplicating Smallpox/Mpox Vaccine.

This cross-sectional study compares the availability and accessibility of mpox vaccine sites with the number of reported cases and allocated vaccines.

Travel Times to Facilities Offering Oral Medication Therapy for COVID-19.

This quality improvement study evaluates access to oral COVID-19 therapeutics within communities in the 48 contiguous states and the District of Columbia.

Beyond "bluespace" and "greenspace": A narrative review of possible health benefits from exposure to other natural landscapes.

Numerous studies have highlighted the physical and mental health benefits of contact with nature, typically in landscapes characterized by plants (i.e., "greenspace") and water (i.e., "bluespace"). However, natural landscapes are not always green or blue, and the effects of other landscapes are worth attention. This narrative review attempts to overcome this limitation of past research. Rather than focusing on colors, we propose that natural landscapes are composed of at least one of three components: (1) plants (e.g., trees, flowering plants, grasses, sedges, mosses, ferns, and algae), (2) water (e.g., rivers, canals, lakes, and oceans), and/or (3) rocks and minerals, including soil. Landscapes not dominated by plants or liquid-state water include those with abundant solid-state water (e.g., polar spaces) and rocks or minerals (e.g., deserts and caves). Possible health benefits of solid-state water or rock/mineral dominated landscapes include both shorter-term (e.g., viewing images) and longer-term (e.g., living in these landscapes) exposure durations. Reported benefits span improved emotional and mental states and medical treatment resources for respiratory conditions and allergies. Mechanisms underlying the health benefits of exposure consist of commonly discussed theories in the "greenspace" and "bluespace" literature (i.e., instoration and restoration) as well as less discussed pathways in that literature (i.e., post-traumatic growth, self-determination, supportive environment theory, and place attachment). This is the first review to draw attention to the potential salutogenic value of natural landscapes beyond "greenspace" and "bluespace." It is also among the first to highlight the limitations and confusion that result from classifying natural landscapes using color. Since the extant literature on natural landscapes - beyond those with abundant plants or liquid-state water - is limited in regard to quantity and quality, additional research is needed to understand their restorative potential and therapeutic possibilities.

Impact of a Medical Clinic Relocation on Travel Time: A Tale of 2 Modes of Transportation.

The aim of this study was to quantify access disparities by examining the impact of a medical clinic relocation on travel time differences for patients using private cars versus public transit. Longitude and latitude of patient home addresses were extracted from electronic medical records for the 4 years before the clinic move. Using offline, open-source, and HIPAA-compliant routing software, roundtrip travel times were computed from each home address to the old and new clinic locations via car and bus. Mean roundtrip travel time by a car changed from 41.3 (IQR 16.1-80.7) to 45.4 (IQR 25.9-78.1) minutes, a 9.9% increase. Mean roundtrip travel time by public transit changed from 67.5 (IQR 51.5-100.2) to 120.8 (100.3-156.1) minutes, a 78.9% increase. Even clinic relocations that minimally impact car travel times can nevertheless yield substantial changes to those traveling by public transit. Clinics and health systems that wish to reduce barriers to accessing health care, especially among those already facing structural inequities, would benefit from utilizing the analytic approach described here.

Pharmacy deserts: More than where pharmacies are.

BACKGROUND: In the United States, geographic access is a major driver of health care disparities. Studies have shown that pharmacy deserts are prevalent in the United States, even in major metropolitan areas. However, one limitation often cited by these studies is the use of distance rather than travel time to define pharmacy deserts. OBJECTIVE: The aim of this study was to assess pharmacy deserts using travel time and to provide a more holistic approach by incorporating analysis of private vehicles and public transportation. METHODS: Pharmacy details were collected from the National Provider Identifier database and neighborhood characteristics from collected census data for the four largest U.S. cities. Pharmacy access was evaluated using open-source routing engines. We determined neighborhoods in pharmacy deserts using both distance and travel time analyses. Sensitivity analysis was performed to determine changes to pharmacy deserts based on small changes in travel time. RESULTS: Of 4654 neighborhoods identified in the four cities of interest, 670 (14.4%) neighborhoods were in pharmacy deserts based on distance. Despite accounting for 28.9% of all neighborhoods, predominantly white neighborhoods only accounted for 4.3% of pharmacy deserts. When evaluating pharmacy deserts by car and public transportation, predominantly white neighborhoods accounted for 2.3% and 1.7% of total pharmacy deserts, respectively. Finally, by reducing travel time from 15 minutes to 10 minutes, pharmacy deserts by car and public transportation increased by 105% and 199%, respectively. All but 3 of the new pharmacy deserts found in the sensitivity analysis were found in nonpredominantly white neighborhoods. CONCLUSION: Using travel time and incorporating modes of transportation, we found that disparities in pharmacy access are more than just where pharmacies are located geographically. There are additional layers of disparities, such as access to public transportation, that need to be addressed to reduce the number of pharmacy deserts.

Relation of Cigarette Smoking and Heart Failure in Adults ≥65 Years of Age (From the Cardiovascular Health Study).

Cigarette smoking is associated with adverse cardiac outcomes, including incident heart failure (HF). However, key components of potential pathways from smoking to HF have not been evaluated in older adults. In a community-based study, we studied cross-sectional associations of smoking with blood and imaging biomarkers reflecting mechanisms of cardiac disease. Serial nested, multivariable Cox models were used to determine associations of smoking with HF, and to assess the influence of biochemical and functional (cardiac strain) phenotypes on these associations. Compared with never smokers, smokers had higher levels of inflammation (C-reactive protein and interleukin-6), cardiomyocyte injury (cardiac troponin T [hscTnT]), myocardial "stress"/fibrosis (soluble suppression of tumorigenicity 2 [sST2], galectin 3), and worse left ventricle systolic and diastolic function. In models adjusting for age, gender, and race (DEMO) and for clinical factors potentially in the causal pathway (CLIN), smoking exposures were associated with C-reactive protein and interleukin-6, sST2, hscTnT, and with N-terminal pro-brain natriuretic protein (in Whites). In DEMO adjusted models, the cumulative burden of smoking was associated with worse left ventricle systolic strain. Current smoking and former smoking were associated with HF in DEMO models (hazard ratio 1.41, 95% confidence interval 1.22 to 1.64 and hazard ratio 1.14, 95% confidence interval 1.03 to 1.25, respectively), and with current smoking after CLIN adjustment. Adjustment for time-varying myocardial infarction, inflammation, cardiac strain, hscTnT, sST2, and galectin 3 did not materially alter the associations. Smoking was associated with HF with preserved and decreased ejection fraction. In conclusion, in older adults, smoking is associated with multiple blood and imaging biomarker measures of pathophysiology previously linked to HF, and to incident HF even after adjustment for clinical intermediates.

Time Spent in Nature Is Associated with Increased Pro-Environmental Attitudes and Behaviors.

Urbanization, screen dependency, and the changing nature of childhood and parenting have led to increased time indoors, creating physical and emotional distancing from nature and time spent in natural environments. Substantial evidence from observational and intervention studies indicates that overall time spent in nature leads to increased perceived value for connectedness to nature and, subsequently, greater pro-environmental attitudes and behaviors (PEAB). This narrative review of the recent literature evaluates associations between time spent in nature with values ascribed to nature and nature connectedness, as well as PEAB. We discuss the influence of nature exposure and education in childhood on subsequent development of PEAB in adulthood. We analyze theoretical frameworks applied to this research as well as metrics employed, populations studied, and individual and societal values before presenting limitations of this research. We conclude with suggestions for future research directions based on current knowledge, underscoring the importance of promoting time spent in nature and PEAB in the face of growing challenges to planetary health. Research indicates that overall time spent in nature, regardless of the quality of environmental conditions, leads to increased perceived values ascribed to nature, which is associated with PEAB; however, this literature is predominantly cross-sectional. Furthermore, personal and social factors may influence PEAB. Thus, more longitudinal studies that consider these factors are needed to assess the duration and frequency of time spent in nature in childhood and its impact on PEAB throughout the life course. Identifying contexts which cultivate PEAB and reverse alienation from nature beginning in childhood may better sensitize adults to the urgency of environmental issues such as climate change, which adversely impact individual and environmental health.

Intercountry Differences in Guideline-Directed Medical Therapy and Outcomes Among Patients With Heart Failure.

OBJECTIVES: The aim of this study was to examine patterns of care and clinical outcomes among patients with heart failure with reduced ejection fraction (HFrEF) in the United States and Canada. BACKGROUND: In the GUIDE-IT (Guiding Evidence Based Therapy Using Biomarker Intensified Treatment) trial, the use of N-terminal pro-B-type natriuretic peptide-guided titration of guideline-directed medical therapy (GDMT) was compared with usual care alone for patients with HFrEF in the United States and Canada. It remains unknown whether the country of enrollment had an impact on outcomes or GDMT use. METHODS: A total of 894 patients at 45 sites across the United States and Canada with HFrEF (ejection fraction ≤40%) were enrolled in the trial. Kaplan-Meier survival estimates stratified by country of enrollment were developed for the trial outcomes, and log-rank testing was compared between the groups. GDMT use and titration were also compared. RESULTS: U.S. patients were more likely to be younger, to be Black, to have higher body mass index, and to have histories of defibrillator placement or sleep apnea. Use of ß-blockers was significantly higher in Canada at baseline (99.3% vs. 94.0%; p = 0.01) and 6 months (99.0% vs. 94.1%; p = 0.04), and use of mineralocorticoid receptor antagonists was higher in Canada at 6 months (68.3% vs. 55.1%; p = 0.01). Canadian patients were less likely to experience the primary study endpoint (hazard ratio [HR]: 0.65; 95% confidence interval [CI]: 0.45 to 0.93; p = 0.01) due to decreased rates of HF hospitalization (HR: 0.57; 95% CI: 0.38 to 0.86; p = 0.003). The differences in outcomes were driven by increased heart failure hospitalization among U.S. Black patients. CONCLUSIONS: In GUIDE-IT, patients with HFrEF in Canada were significantly less likely to be hospitalized for heart failure. Differences in GDMT use, along with differences in sociodemographics and care delivery structures, may contribute to these differences, highlighting the importance of increasing diversity in clinical trials. (Guiding Evidence Based Therapy Using Biomarker Intensified Treatment [GUIDE-IT]; NCT01685840).

Glucagon use by U.S. adults with type 1 and type 2 diabetes.

The American Diabetes Association recommends that all patients at risk for hypoglycemia be prescribed glucagon. Despite this recommendation, there is evidence that prescription rates are lower than expected for patients with type 1 and type 2 diabetes. This study investigated prescription patterns for glucagon among de-identified administrative claims from OptumLabs® Data Warehouse for prescriptions between January 1, 2014 and December 31, 2014 among pharmacologically treated type 1 and 2 diabetes patients. We find that glucagon was rarely filled by patients with type 1 and type 2 diabetes, including fewer than 5% of patients with prior hypoglycemia requiring emergency healthcare utilization. Among patients with type 1 diabetes, glucagon fills were unpredictable and not targeted to highest risk patients.

Accuracy of Height Measurement in the Inpatient Setting.

Accurate height measurement is critical for accurate dosing of medications, mechanical ventilation, and nutritional calculations. Prior research has identified inaccuracies with self-reported height, and height is notably important to measure accurately in critically ill patients. In this study, conducted in a large tertiary academic medical center, medical records rarely indicated the method of height measurement, and there were statistically significant variations in measured height across admissions.