plantMASST - Community-driven chemotaxonomic digitization of plants.

Understanding the distribution of hundreds of thousands of plant metabolites across the plant kingdom presents a challenge. To address this, we curated publicly available LC-MS/MS data from 19,075 plant extracts and developed the plantMASST reference database encompassing 246 botanical families, 1,469 genera, and 2,793 species. This taxonomically focused database facilitates the exploration of plant-derived molecules using tandem mass spectrometry (MS/MS) spectra. This tool will aid in drug discovery, biosynthesis, (chemo)taxonomy, and the evolutionary ecology of herbivore interactions.

New forays into measurement of ocular biomechanics.

PURPOSE OF REVIEW: The field of corneal biomechanics has rapidly progressed in recent years, reflecting technological advances and an increased understanding of the clinical significance of measuring these properties. This review will evaluate in-vivo biomechanical properties obtained by current technologies and compare them regarding their relevance to established biomechanical properties obtained by gold-standard ex-vivo techniques normally conducted on elastic materials. RECENT FINDINGS: Several new technologies have appeared in recent years, including vibrational optical coherence tomography (VOCT) and the corneal indentation device (CID). These techniques provide promising new opportunities for minimally invasive and accurate measurements of corneal viscoelastic properties. SUMMARY: Alterations in corneal biomechanics are known to occur in several corneal degenerative diseases and after refractive surgical procedures. The measurement of corneal biomechanical properties has the capability to diagnose early disease and monitor corneal disease progression. Several new technologies have emerged in recent years, allowing for more accurate and less invasive measurements of corneal biomechanical properties, most notably the elastic modulus.

Intraocular pressure profile following selective laser trabeculoplasty in pigmentary and primary open-angle glaucoma.

PURPOSE: To compare the intraocular pressure (IOP) profile and the incidence of IOP spikes following selective laser trabeculoplasty (SLT) between pigmentary glaucoma (PG) and primary open-angle glaucoma (POAG). MATERIALS AND METHODS: Retrospective comparative study of 65 PG eyes of 51 patients matched with 65 POAG eyes of 65 patients who received SLT. Matching was done based on age, gender, glaucoma severity, pre-laser IOP, and number of medications. Post-SLT IOP spike was defined as IOP elevation ≥5mmHg, 30-45 min after the laser. RESULTS: In PG and POAG groups, the average age was 62.33 ± 9.18 and 62.58 ± 9.19 years (p = 0.95). The glaucoma severity (p = 0.708), baseline IOP (PG = 21.61 ± 1.34mmHg vs. POAG = 21.13 ± 5.09mmHg, p = 0.943), and number of topical glaucoma medications(PG = 2.34 ± 1.34 vs. POAG = 2.1 ± 1.41, p = 0.342) were comparable. More PG patients were on oral acetazolamide (PG = 26.15% vs. POAG = 1.5%, p < 0.001). Average logMAR visual acuity was significantly higher in the POAG group (0.207 ± 0.3 vs. 0.192 ± 0.37, p = 0.012). Eyes with PG received lower laser energy (POAG = 63.65 ± 22.03 mJ vs. PG = 43.71 ± 25.68 mJ, p < 0.001). IOP spikes were recorded in 5 PG eyes (7.6%) and none in the POAG group (p = 0.058). Failure rates were similar (PG = 50.7% and POAG = 43.1%, p = 0.205). In multivariable analysis, only pre-laser IOP (coefficient = 2.154 [CI: 0.765-3.543], p = 0.003) was a significant predictor of IOP change percentage after 12 months. CONCLUSIONS: SLT was comparably effective in both PG and POAG. IOP spikes were observed only in the PG group, though the total laser energy was lower in this group compared with POAG.

Quantifying assumptions underlying peak oxygen consumption equations across the body mass spectrum.

The goal of this study is to quantify the assumptions associated with the Wasserman-Hansen (WH) and Fitness Registry and the Importance of Exercise: A National Database (FRIEND) predictive peak oxygen consumption (pVO2 ) equations across body mass index (BMI). Assumptions in pVO2 for both equations were first determined using a simulation and then evaluated using exercise data from the Stanford Exercise Testing registry. We calculated percent-predicted VO2 (ppVO2 ) values for both equations and compared them using the Bland-Altman method. Assumptions associated with pVO2 across BMI categories were quantified by comparing the slopes of age-adjusted VO2 ratios (pVO2 /pre-exercise VO2 ) and ppVO2 values for different BMI categories. The simulation revealed lower predicted fitness among adults with obesity using the FRIEND equation compared to the WH equations. In the clinical cohort, we evaluated 2471 patients (56.9% male, 22% with BMI >30 kg/m2 , pVO2 26.8 mlO2 /kg/min). The Bland-Altman plot revealed an average relative difference of -1.7% (95% CI: -2.1 to -1.2%) between WH and FRIEND ppVO2 values with greater differences among those with obesity. Analysis of the VO2 ratio to ppVO2 slopes across the BMI spectrum confirmed the assumption of lower fitness in those with obesity, and this trend was more pronounced using the FRIEND equation. Peak VO2 estimations between the WH and FRIEND equations differed significantly among individuals with obesity. The FRIEND equation resulted in a greater attributable reduction in pVO2 associated with obesity relative to the WH equations. The outlined relationships between BMI and predicted VO2 may better inform the clinical interpretation of ppVO2 values during cardiopulmonary exercise test evaluations.

Being fit in the COVID-19 era and future epidemics prevention: Importance of cardiopulmonary exercise test in fitness evaluation.

Endurance and resistance physical activity have been shown to stimulate the production of immunoglobulins and boost the levels of anti-inflammatory cytokines, natural killer cells, and neutrophils in the bloodstream, thereby strengthening the ability of the innate immune system to protect against diseases and infections. Coronavirus disease 19 (COVID-19) greatly impacted people's cardiorespiratory fitness (CRF) and health worldwide. Cardiopulmonary exercise testing (CPET) remains valuable in assessing physical condition, predicting illness severity, and guiding interventions and treatments. In this narrative review, we summarize the connections and impact of COVID-19 on CRF levels and its implications on the disease's progression, prognosis, and mortality. We also emphasize the significant contribution of CPET in both clinical evaluations of recovering COVID-19 patients and scientific investigations focused on comprehending the enduring health consequences of SARS-CoV-2 infection.

Assessing cardiorespiratory fitness in clinical and community settings: Lessons and advancements in the 100th year anniversary of VO2max.

Cardiorespiratory fitness (CRF) is a well-established biomarker that has applications to all adults across the health and disease spectrum. Despite overwhelming evidence supporting the prognostic utility of CRF, it remains vastly underutilized. CRF is optimally measured via cardiopulmonary exercise testing which may not be feasible to implement on a large scale. Therefore, it is prudent to develop ways to accurately estimate CRF that can be applied in clinical and community settings. As such, several prediction equations incorporating non-exercise information that is readily available from routine clinical encounters have been developed that provide an adequate reflection of CRF that could be implemented to raise awareness of the importance of CRF. Further, technological advances in smartphone apps and consumer-grade wearables have demonstrated promise to provide reasonable estimates of CRF that are widely available, which could enhance the utilization of CRF in both clinical and community settings.

Update to the 2016 American Heart Association cardiorespiratory fitness statement.

In 2016 the American Heart Association published a scientific statement that summarized a large body of evidence concluding that cardiorespiratory fitness (CRF) was a powerful marker of cardiovascular disease (CVD) and CVD-mortality risk; its association with morbidity and mortality was independent of commonly obtained risk factors, and consequently, that it should be a routine measure in all health care settings. Since 2016 the interest in CRF as a prognostic for human health and performance has increased exponentially. This review will summarize a growing body of evidence that reinforces the notion that the assessment of CRF improves patient/client management. Feasible means of CRF assessment in health care settings is considered, and the expected response of CRF to exercise consistent with consensus recommendations is reviewed. The association between CRF and health care costs is also explored. The evidence reviewed will reinforce the conclusions drawn in 2016; that overwhelming evidence demands that CRF should be a routine assessment in all health care settings - a vital sign.

2023 update: The importance of cardiorespiratory fitness in the United States.

The American Heart Association issued a Policy Statement in 2013 that characterized the importance of cardiorespiratory fitness (CRF) as an essential marker of health outcomes and specifically the need for increased assessment of CRF. This statement summarized the evidence demonstrating that CRF is "one of the most important correlates of overall health status and a potent predictor of an individual's future risk of cardiovascular disease." Subsequently, this Policy Statement led to the development of a National Registry for CRF (Fitness Registry and the Importance of Exercise: A National Data Base [FRIEND]) which established normative reference values for CRF for adults in the United States (US). This review provides an overview of the progress made in the past decade to further our understanding of the importance of CRF, specifically related to prevention and for clinical populations. Additionally, this review overviews the evolvement and additional uses of FRIEND and summarizes a hierarchy of assessment methods for CRF. In summary, continued efforts are needed to expand the representation of data from across the US, and to include data from pediatric populations, to further develop the CRF Reference Standards for the US as well as further develop Global CRF Reference Standards.

Phenotyping cardiopulmonary exercise testing measures in heart failure with reduced ejection fraction: A comparison between Italy and Brazil.

BACKGROUND: While patients with heart failure (HF) with reduced left ventricular ejection fraction (HFrEF) constitutes a global health crisis the incidence, prevalence and prognosis of the disease may differ depending on the continent and country. OBJECTIVE: To profile, analyze and compare cardiopulmonary exercise testing (CPET) data of patients with HFrEF between Italian and Brazilian cohorts. METHODS: In this observational study, a total of 630 patients with clinical and functional diagnosis of HFrEF (315 patients from Brazil and 315 patients from Italy) performed CPET. RESULTS: Although Brazilian patients were slightly younger (Brazil 60±10 vs Italy 64±11 p<0.001) with a better peak oxygen consumption (V̇O2), circulatory power and left ventricular ejection fraction (LVEF) (p<0.01), ventilatory inefficiency and oscillation ventilation was higher when compared to the Italian cohort. When stratifying patients with LVEF≤30 % and age≥60 years, Brazilian patients presented worse ventilatory efficiency, and lower peak V̇O2 compared to the Italian cohort. CONCLUSION: Patients with HFrEF from Brazil exhibited higher ventilatory inefficiency and a greater prevalence of oscillatory ventilation during CPET compared to patients with the same diagnosis from Italy.

Improving Reporting of Exercise Capacity Across Age Ranges Using Novel Workload Reference Equations.

Exercise capacity (EC) is an important predictor of survival in the general population and in subjects with cardiopulmonary disease. Despite its relevance, considering the percent-predicted workload (%pWL) given by current equations may overestimate EC in older adults. Therefore, to improve the reporting of EC in clinical practice, our main objective was to develop workload reference equations (pWL) that better reflect the relation between workload and age. Using the Fitness Registry and the Importance of Exercise National Database (FRIEND), we analyzed a reference group of 6,966 apparently healthy participants and 1,060 participants with heart failure who underwent graded treadmill cardiopulmonary exercise testing. For the first group, the mean age was 44 years (18 to 79); 56.5% of participants were males and 15.4% had obesity. Peak oxygen consumption was 11.6 ± 3.0 METs in males and 8.5 ± 2.4 METs in females. After partition analysis, we first developed sex-specific pWL equations to allow comparisons to a healthy weight reference. For males, pWL (METs) = 14.1-0.9×10-3×age2 and 11.5-0.87×10-3×age2 for females. We used those equations as denominators of %pWL, and based on their distribution, we determined thresholds for EC classification, with average EC defined by the range corresponding to 85% to 115%pWL. Compared with %pWL using current equations, the new equations yielded better-calibrated %pWL across different age ranges. We also derived body mass index-adjusted pWL equations that better assessed EC in subjects with heart failure. In conclusion, the novel pWL equations have the potential to impact the report of EC in practice.

Long-Term Surgical Outcomes of Glaucoma Drainage Implants in Eyes with Preoperative Intraocular Pressure Less than 19 mmHg.

Background: This retrospective review reports on patients who underwent glaucoma drainage implant (GDI) surgery and had baseline intraocular pressure (IOP) of ≤18 mmHg with at least one year of follow-up. Methods: Clinical data of 67 eyes of 67 patients were collected from patients' charts, and the outcomes of GDI were evaluated until 7 years. GDI failure was defined as IOP reduction of less than 20% from the baseline at two consecutive visits three months after surgery, decline to no light perception, or if additional glaucoma surgery was performed. Results: The average age was 65.9 ± 13.2 years. Most cases were male (52.2%), White (53.7%), and had primary open-angle glaucoma (62.7%). Forty-four eyes had prior glaucoma surgery (68.6%) and 46 (68.6%) had severe glaucoma. Though postoperative (postop) IOP changes were insignificant, the average postop number of medications dropped from 2.4 ± 1.4 to 1.9 ± 1.2 medications two years after surgery (p = 0.0451). Postop complications (23.9%) included GDI exposure (7.5%), inflammation (4.5%), shallow anterior chamber (4.5%), and strabismus (1.5%). Hypotony was observed in 4 eyes (5.9%), none of which developed hypotony maculopathy. The cumulative one-year failure rate was 56.7%, most of which were due to failure to lower IOP. Conclusion: In patients with baseline IOP ≤18 mmHg who had GDI surgery, though the change in IOP was not statistically significant, the number of medications dropped and visual field progression slowed in a subset of patients with adequate perimetric data. Due to a relatively high rate of complications and limited effectiveness in lowering IOP, GDI should be cautiously used in these eyes.

Multimodal Exercise and Cognitive Training Program Improves Cognitive Function in Amnestic Mild Cognitive Impairment.

OBJECTIVE: To investigate the preliminary efficacy of a combined physical exercise + cognitive training intervention for older adults with amnestic mild cognitive impairment (aMCI). DESIGN: Randomized clinical trial. SETTING: Veteran Affairs Hospital, Palo Alto, CA. PARTICIPANTS: Sample included 72 community-dwelling volunteers (mean age 72.4 ± 9.5) diagnosed with aMCI. INTERVENTION: Participants were randomized to either a combined aerobic and resistance exercise + cognitive training (CARE+CT) or stretching exercise + CT (SE+CT). MEASUREMENTS: Primary outcomes included intervention specific assessments of word list and name-face recall. Secondary cognitive outcomes included standardized composite scores that reflect cognitive domains (e.g., learning and memory, executive function, processing speed, visuospatial ability, language). Secondary physiological outcomes included VO2 max and functional capacity (e.g., distance walked 6-minute walk test). APOE and BDNF were determined from whole blood samples. RESULTS: Controlling for age and employment status, linear mixed effects models revealed that all participants experienced significant improvement in the delayed recall of word list, learning and memory and executive function. Only the CARE+CT condition had significant improvement in processing speed and functional capacity. APOE4 status impacted cognitive benefits of those in the SE+CT condition. CONCLUSIONS: Results provide preliminary support for combined exercise and cognitive training interventions for older adults with aMCI. Further research is needed to understand the mechanisms involved as well as the impact of these interventions in diverse samples. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01962038.

The Association between Cardiorespiratory Fitness and the Risk of Breast Cancer in Women.

INTRODUCTION: Studies have shown an inverse association between the risk of breast cancer in women and physical activity. However, information on the association between cardiorespiratory fitness (CRF) assessed objectively by a standardized test and the risk of developing breast cancer is limited. PURPOSE: To examine the CRF-breast cancer risk association in healthy females. METHODS: This retrospective study was derived from the Exercise Testing and Health Outcomes Study cohort ( n = 750,302). Female participants ( n = 44,463; mean age ± SD; 55.1 ± 8.9 yr) who completed an exercise treadmill test evaluation (Bruce protocol) at the Veterans Affairs Medical Centers nationwide from 1999 to 2020 were studied. The cohort was stratified into four age-specific CRF categories (Least-fit, Low-fit, Moderate-fit, and Fit), based on the peak METs achieved during the exercise treadmill test. RESULTS: During 438,613 person-years of observation, 994 women developed breast cancer. After controlling for covariates, the risk of breast cancer was inversely related to exercise capacity. For each 1-MET increase in CRF, the risk of cancer was 7% lower (HR, 0.93; 95% CI, 0.90-0.95; P < 0.001). When risk was assessed across CRF categories with the Least-fit group as the referent, the risk was 18% lower for Low-fit women (HR, 0.82; 95% CI, 0.70-0.96; P = 0.013), 31% for Moderate-fit (HR, 0.69; 95% CI, 0.58-0.82; P < 0.001), and 40% for Fit (HR, 0.60; 95% CI, 0.47-0.75; P < 0.001). CONCLUSIONS: We observed an inverse and graded association between CRF and breast cancer risk in women. Thus, encouraging women to improve CRF may help attenuate the risk of developing breast cancer.

Attenuation of the increase of heart rate and oxygen consumption during progressive exercise in professional rugby players.

BACKGROUND: The response of oxygen uptake (VO2) and heart rate (HR) to continuous progressive large muscle mass exercise is not always linear. This study aimed to compare the patterns of the Speed/VO2 (S/VO2) and speed/HR (S/HR) relationships during an incremental treadmill-running test in professional rugby players. METHODS: Fourteen professional rugby athletes performed a maximal incremental treadmill-running test, following the Conconi test protocol. Speed, heart rate, and gas exchange parameters were recorded. The slope of the S/VO2 and S/HR relationships were mathematically determined. RESULTS: The S/VO2 and S/HR relationships were linear up to a submaximal speed and curvilinear thereafter. The speed of locomotion at which the slope of the S/VO2 and S/HR relationships start to attenuate (VO2att and HRatt) were coincident (12.3±1.0 and 12.4±0.9 km/h), strongly correlated and in good agreement. VO2 values at VO2att (44.9±8.7 mL/kg/min) were significantly correlated with VO2 values at the ventilatory threshold (43.3±6.0 mL/kg/min) (R2=0.83, P=0.001) and in good agreement. The running speed/VO2 ratio (ΔS/ΔVO2) up to VO2att was significantly lower than that beyond VO2att (2.98±1.1 vs. 5.16±2.31); P<0,001). CONCLUSIONS: The speed/oxygen uptake and S/HR relationships during progressive exercise start to attenuate at a coincident exercise intensity, and at oxygen uptake values strongly correlated with the ventilatory threshold. These findings further support the usefulness of the attenuation of the S/HR relationship as a practical tool for exercise testing and training purposes in professional rugby players.

Change in Peak Oxygen Uptake Predicted by the Moderate 1-km Treadmill Walking Test After Walking Training in Outpatients With Cardiovascular Disease.

PURPOSE: The purpose of this study was to determine the ability of the moderate 1-km treadmill walking test (1km-TWT) to predict changes in peak oxygen uptake (V˙O 2peak ) in patients with stable cardiovascular disease (CVD) during an exercise-based secondary prevention program. METHODS: Sixty-four male outpatients with stable CVD (age 64 [41-85] yr) performed the 1km-TWT before and after an 8-wk walking training program. Patient V˙O 2peak was estimated using a sex-specific equation including age, body mass index, 1km-TWT performance time, and heart rate (V˙O 2peakEST ). Forty-one patients completed a maximal cardiopulmonary treadmill test (CPX) for direct V˙O 2peak determination (V˙O 2peakMEAS ). The training prescription consisted of moderate-to-high intensity supervised walking for 30-40 min/session, and an additional 2-4 times/wk of unsupervised home moderate walking sessions between 20-60 min at the end of the program. The walking intensity was based on the results of the 1km-TWT. RESULTS: Patients participated in an average of 14 of the 16 supervised sessions. An overall significant improvement in V˙O 2peakMEAS and weekly recreational physical activity levels were observed. No differences were observed between V˙O 2peakMEAS and V˙O 2peakEST . Compared with CPX results, the 1km-TWT underestimated the V˙O 2peak increase after the exercise intervention (mean difference -0.3 mL/kg/min, P > .05). CONCLUSIONS: The 1km-TWT provides a reasonably accurate and simple tool to predict changes in V˙O 2peak due to moderate walking training in male outpatients with CVD. These findings contribute to the growing body of evidence supporting the use of the 1km-TWT for exercise testing and training purposes in the context of cardiac rehabilitation/secondary prevention programs.

Progression to Insulin Therapy in Patients With Type 2 Diabetes According to Cardiorespiratory Fitness, Body Mass Index, and Statin Therapy.

OBJECTIVE: To evaluate the association between statin therapy, cardiorespiratory fitness (CRF), body mass index (BMI), and progression to insulin therapy in type 2 diabetes mellitus (T2DM). METHODS: Participants were patients with T2DM (mean age, 62.7±8.4 years; men, 178,992; women, 8360) not treated with insulin, with no evidence of uncontrolled cardiovascular disease, who completed an exercise treadmill test between October 1, 1999, and September 3, 2020. Of these, 158,578 were treated with statins and 28,774 were not. We established 5 age-specific CRF categories according to peak metabolic equivalents of task achieved during an exercise treadmill test. RESULTS: During a median follow-up period of 9.0 years, 51,182 patients progressed to insulin therapy with an average annual incidence rate of 28.4 events/1000 person-years. The adjusted progression rate was 27% higher in statin-treated patients (hazard ratio [HR], 1.27; 95% CI, 1.24 to 1.31), related directly to BMI and inversely related to CRF. A progressively higher rate was noted in statin-treated vs non-statin-treated patients within all BMI categories, ranging from 23% for normal weight to 90% for those with BMI of 35 kg/m2 and higher. The statin-CRF interaction revealed 43% higher rate in the least-fit statin-treated patients (HR, 1.43; 95% CI, 1.35 to 1.51) and a progressive decline with increased CRF to 30% lower risk in highly fit statin-treated patients (HR, 0.70; 95% CI, 0.66 to 0.75). CONCLUSION: In patients with T2DM, the statin-related progression to insulin therapy was associated with relatively low CRF and high BMI levels. The progression rate was mitigated by increased CRF regardless of BMI. Clinicians should foster regular exercise for patients with T2DM to enhance CRF and to lessen the rate of progression to insulin therapy.

Early Postoperative Aqueous Suppression Therapy and Surgical Outcomes of Ahmed Tube Shunts in Refractory Glaucoma.

PURPOSE: To compare early vs. delayed use of aqueous suppressants on Ahmed glaucoma valve (AGV) outcomes. DESIGN: Single-center retrospective comparative case series. PARTICIPANTS: Patients who underwent AGV surgery at Wills Eye Hospital in the period between 2016 and 2021. METHODS: Retrospective review of AGV surgery at Wills Eye Hospital 2016 to 2021 for refractory glaucoma. Two groups were created: group 1 or those who received early aqueous suppressant therapy in the first 2 weeks postoperatively whenever the intraocular pressure (IOP) was > 10 mmHg, and group 2 or those who received delayed treatment after 2 weeks whenever the IOP exceeded the target pressure. Aqueous suppressant therapy included topical beta blockers, carbonic anhydrase inhibitors, and/or alpha agonists. MAIN OUTCOME MEASURES: The primary outcome measures were the frequency of hypertensive phase (HP) defined as IOP > 21 mmHg in first 3 months after an initial reduction to 21 mmHg or less in the first postoperative week not caused by tube obstruction or retraction, and month-12 surgical failure defined as 5 ≥ IOP > 21 mmHg on 2 consecutive visits, vision decline to no light perception (NLP), or glaucoma reoperation. Secondary outcome measures included changes in visual acuity (VA), IOP, and glaucoma medications at 12 months. Predictive factors for surgical failure were also identified. RESULTS: A total of 407 eyes of 391 patients (260 in group 1, 147 in group 2) with similar baseline characteristics were included. Hypertensive phase was more common in group 2 than 1 (41.5% vs. 18.5%; P < 0.001). At month 12 (N = 303 eyes), group 1 was less likely to fail than group 2 (21.2% vs. 36.8%, P = 0.003). Multivariate regression analysis showed that HP (odds ratio [OR] = 10.47, P < 0.001), delayed aqueous suppression use (OR = 2.17, P = 0.003), and lower baseline VA (OR = 1.56, P = 0.015) were the strongest predictors of month-12 failure. CONCLUSIONS: Early use of aqueous suppressants may lower the risk of HP and improve AGV outcomes. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Empowering Family Glaucoma Risk Communication Using QR-Code-Mediated Online Intervention.

PURPOSE: Attempts at engaging relatives of glaucoma patients in education and screening have had limited success. This study explores the feasibility of an electronic intervention to facilitate direct yet reliable glaucoma risk communication between open-angle glaucoma patients (probands) and their first-degree relatives (FDRs). DESIGN: Prospective survey and assessment of intervention. PARTICIPANTS: Fifty adult probands, engaging 140 FDRs. METHODS: Phase I was an iterative process involving creating a customized website and Quick Response (QR)-code-based intervention designed with input from probands, FDRs of patients, community members, and researchers. In phase II, the intervention was deployed in a clinical setting; this involved recruiting probands who had a smartphone and were willing to use the QR-code to message their FDRs a standard message, including a website link about glaucoma risk in FDRs and the importance of getting examined. Follow-up interviews were conducted with probands 1 to 2 weeks after their clinic visit to assess the impact of the intervention. Demographic data, website analytics, and participant feedback were collected and analyzed. MAIN OUTCOME MEASURES: Increased awareness of glaucoma risk among FDRs and enhanced discussions. RESULTS: At the time of the first interview, probands reported that 70% of the FDRs were aware of the probands' glaucoma diagnosis, but only 26% had undergone glaucoma screening. Ninety percent of probands had no issues using the QR-codes. Website analytics recorded 73 visits from 51 distinct internet protocol addresses (IPs). After receiving the standard message, 95% of FDRs followed up with the probands, actively discussing glaucoma. Of the probands, 84% completed the follow-up interview 1 to 2 weeks after enrollment. Fifty-nine percent of the FDRs were reported to have scheduled screening appointments. The collected feedback revealed that 96% of probands found the intervention helpful, fostering glaucoma discussions with their FDRs and improving probands' comfort level in discussing health issues with FDRs from baseline (very comfortable: 88%, comfortable: 8%, neutral: 2%, and very uncomfortable: 2%) to the follow-up interview (very comfortable: 98% and comfortable: 2%). CONCLUSIONS: This innovative online method of communicating the risk of glaucoma to FDRs of probands prompted and increased the comfort level of familial discussions of glaucoma. More than half of FDRs reported making an appointment to get screened for glaucoma. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Cardiorespiratory fitness and risk of heart failure with preserved ejection fraction.

AIMS: Preventive strategies for heart failure with preserved ejection fraction (HFpEF) include pharmacotherapies and lifestyle modifications. However, the association between cardiorespiratory fitness (CRF) assessed objectively by a standardized exercise treadmill test (ETT) and the risk of HFpEF has not been evaluated. Thus, we evaluated the association between CRF and HFpEF incidence. METHODS AND RESULTS: We assessed CRF in US Veterans (624 551 men; mean age 61.2 ± 9.7 years and 43 179 women; mean age 55.0 ± 8.9 years) by a standardized ETT performed between 1999 and 2020 across US Veterans Affairs Medical Centers. All had no evidence of heart failure or myocardial infarction prior to completion of the ETT. We assigned participants to one of five age- and gender-specific CRF categories (quintiles) based on peak metabolic equivalents (METs) achieved during the ETT and four categories based on CRF changes in those with two ETT evaluations (n = 139 434) ≥1.0 year apart. During a median follow-up of 10.1 years (interquartile range 6.0-14.3 years), providing 6 879 229 person-years, there were 16 493 HFpEF events with an average annual rate of 2.4 events per 1000 person-years. The adjusted risk of HFpEF decreased across CRF categories as CRF increased, independent of comorbidities. For fit individuals (≥10.5 METs) the hazard ratio (HR) was 0.48 (95% confidence interval [CI] 0.46-0.51) compared with least fit (≤4.9 METs; referent). Being unfit carried the highest risk (HR 2.88, 95% CI 2.67-3.11) of any other comorbidity. The risk of unfit individuals who became fit was 37% lower (HR 0.63, 95% CI 0.57-0.71), compared to those who remained unfit. CONCLUSIONS: Higher CRF levels are independently associated with lower HFpEF in a dose-response manner. Changes in CRF reflected proportional changes in HFpEF risk, suggesting that the HFpEF risk was modulated by CRF.

Cardiorespiratory Fitness and Incidence of Digestive System Cancers in Men.

PURPOSE: To assess the association between cardiorespiratory fitness (CRF) and incidence of digestive system cancers (DSCs) in men. METHODS: A prospective cohort of 4,540 men aged 55.2 ± 13.1 years who were free from malignancy at baseline was studied. Exposure was CRF quantified from treadmill exercise testing (individualized ramp protocol) in metabolic equivalents (METs). Incidence of DSCs was the primary outcome, utilizing medical records of any new diagnosed DSC. Cox proportional hazard analyses were conducted adjusting for established cancer risk factors. RESULTS: Mean CRF was 8.3 ± 3.5 METs. During 13 ± 7.6 years follow up, 250 (5.5%) DSC cases were diagnosed (colorectal = 163, gallbladder = 46, liver = 23, esophagus = 8, pancreas = 7 and other digestive organ cancers = 3). For each 1-MET increase in CRF there were 6% [Hazard Ratio = 0.94, 95% CI (0.91-0.98), p = 0.006], and 9% [Hazard Ratio = 0.91, 95% CI (0.85-0.97), p = 0.006] lower risks of DSC incidence in the total cohort and among men younger than 60 years old, respectively. Additionally, each 1-MET increase in CRF was associated with 9% lower risks of DSC incidence among never and current smokers. CRF was not associated with DSC incidence among men ≥ 60 years old and among former smokers. CONCLUSION: Higher CRF was associated with lower risk of DSC incidence in men, particularly in those younger than 60 years, and never and current smokers. These findings suggest that higher CRF has potential preventive benefits against the development of DSCs, although additional large studies are needed. CRF screening and achieving higher levels could serve as a complementary preventive strategy for public health.