Nurses' mental workload and public health emergency response capacity in COVID-19 pandemic: A cross-sectional study.

AIMS: The aim of this study was to assess the level of mental workload of Chinese nurses through a latent profile analysis and to explore its relationship with public health emergency response capacity. DESIGN: A cross-sectional design with a convenience sample. METHODS: A convenience sample of nurses from five tertiary hospitals in Chengdu between May and December 2022. Demographic, work-related information, Nurse's version of NASA's Task Load Index Scale and Nurse's Public Health Emergency Response Capacity Scale were used in this study. RESULTS: The mean scores for mental workload and emergency response capacity for nurses were (57.19 ± 15.67) and (3.58 ± 0.77) respectively. We found that the mental workload of nurses fell into three potential categories. In addition, there were differences in psychological training and supply of epidemic prevention materials in the department among nurses with different mental workload subtypes. There was a moderate negative correlation between nurses' mental workload and public health emergency response capacity. CONCLUSION: Our results show that there is still a strong mental workload on a proportion of nurses, and enhanced psychological training and material supply support are beneficial in relieving nurses' mental workload. The better the nurses' capacity to cope with public health emergencies, the lower their mental workload. IMPACT: Nursing managers should pay ongoing attention to the mental workload status of nurses in the latter stages of a pandemic and individual differences in nurses' mental workload. In addition, nursing managers should be aware of the impact of public health emergency response capacity on nurses' mental workload. They can intervene in nurses mental workload from a new perspective. PATIENT OR PUBLIC CONTRIBUTION: 560 registered nurses participated in this study.

The prevalence and factors of posttraumatic growth among nurses based on the PTGI: A systematic review and meta-analysis.

BACKGROUND: The urgency and risk of clinical nursing may cause nurses to experience traumatic stress, but it may also lead to posttraumatic growth. However, no study has comprehensively analyzed the prevalence of posttraumatic growth among nurses using a unified outcome measure and a validated assessment tool. AIM: This study aims to systematically assess the prevalence and factors of posttraumatic growth among nurses based on the Posttraumatic Growth Inventory (PTGI). METHODS: Ten databases, including The Cochrane Library, PubMed, Web of Science, CINAHL, Springerlink, Embase, Chinese Biomedical (CBM), China National Knowledge Infrastructure (CNKI), WanFang, and VIP databases, were searched as of December 31, 2022. The prevalence of posttraumatic growth was pooled using Stata 17.0 software. The PRISMA guideline was used to report the systematic review and meta-analysis. PROSPERO registration number: CRD42022365620. RESULTS: A total of 30 studies were included in this systematic review and meta-analysis, consisting of 14,022 nurses worldwide from four countries. In our study, the pooled mean score of posttraumatic growth among nurses was 66.34 (95% CI: 61.25-71.43). From 2015 to 2022, nurses' posttraumatic growth levels gradually increased. In addition, Turkey nurses have the lowest posttraumatic growth levelnurses who experienced workplace violence have a lower posttraumatic growth level compared with other nurses; while nurses aged over 30 and male have higher posttraumatic growth levels. CONCLUSIONS: While several studies on the prevalence of posttraumatic growth among nurses have been published, the reported data are quite different. Our systematic review and meta-analysis found that nurses' posttraumatic growth level was "moderate," and nurses' posttraumatic growth may vary based on publication year, country, traumatic event, age, and gender. IMPLICATIONS FOR NURSING AND HEALTH POLICY: Our findings may provide a theoretical basis for hospital administrators and policy makers to scientifically manage human resources, comprehensively evaluate nurses' mental health, and promote nurses' posttraumatic growth in different traumatic events, which is conducive to the formulation and implementation of relevant policy guidelines.

The mediating effect of coping styles between emergency capacity and mental workload among clinical nurses: A cross-sectional study.

AIMS: This study aimed to examine the relationship between emergency capacity, coping styles, and mental workload among nurses. BACKGROUND: Emergency capacity, coping styles, and mental workload are all variables associated with work. Identifying the relationship between these variables can facilitate administrators to implement tailored and effective intervention strategies to improve individual performance, quality of care, and medical safety. METHODS: A quantitative cross-sectional study was carried out to investigate 605 Chinese clinical nurses in seven tertiary hospitals by using personal information form, emergency capacity scale for nurses, simplified coping skill questionnaire, and the NASA-Task Load Index. RESULTS: Emergency capacity and mental workload were found at moderate levels. The multiple linear regression model suggested that spinsterhood, no children, high workload, always anxiety or nervousness, and lower monthly income were the influencing factors of mental workload. Positive coping style was positively correlated with emergency capacity and negatively correlated with mental workload. Negative coping style was negatively related to emergency capacity and positively related to mental workload. Additionally, coping styles played a partial mediating role in the relationship between emergency capacity and mental workload through constructing a structural equation model, but the effects of positive coping style and negative coping style are opposite. CONCLUSION: Our results showed that coping styles played a mediating role in the relationship between emergency capacity and mental workload. Managers can alleviate the mental workload of nurses by cultivating positive coping styles and improving emergency capacity. IMPLICATIONS FOR NURSING AND NURSING POLICY: Mental workload of nurses deserves more attention in medical institutions. The results of our study provide evidence for improving employee health, promoting positive behaviors, and optimizing organizational management. Nursing managers should take feasible measures to fulfill nurses' needs for emergency capacity and coping strategies to alleviate nurses' mental workload, so as to stimulate their intrinsic motivation and positive organizational behavior.

Levels and influencing factors of mental workload among intensive care unit nurses: A systematic review and meta-analysis.

AIM: The purpose of this systematic review was to determine the levels and influencing factors of mental workload in intensive care unit nurses. BACKGROUND: Intensive care unit nurses have a high mental workload level. To our knowledge, no meta-analytic research investigating the levels of mental workload in intensive care unit nurses and related factors has yet been performed. DESIGN: This article is a systematic review and meta-analysis. METHODS: Eleven electronic databases were searched from the database setup dates until 31 December 2022. The research team independently conducted study selection, quality assessments, data extractions and analysis of all included studies. The PRISMA guideline was used to guide reportage of the systematic review and meta-analysis. RESULTS: Seventeen studies were included. In these studies, the pooled mean score of mental workload was 68.07 (95%CI:64.39-71.75). Furthermore, subgroup analyses indicated that intensive care unit nurses' mental workload differed significantly by countries, sample size and publication year. The mental workload influential factors considered were demographic, work-related and psychological factors. CONCLUSION: Hospital administrators should develop interventions to reduce mental workload to enhance the mental health of intensive care unit nurses and nursing care quality. Hospital managers should pay attention to the mental health of nurses and guide them to correctly relieve occupational stress and reduce mental workload.

The levels and related factors of mental workload among nurses: A systematic review and meta-analysis.

AIM: The aim was to determine the overall levels and related factors of mental workload assessed using the NASA-TLX tool among nurses. BACKGROUND: Mental workload is a key element that affects nursing performance. However, there exists no review regarding mental workload assessed using the NASA-TLX tool, focusing on nurses. DESIGN: A systematic review and meta-analysis. DATA SOURCES: PubMed, MEDLINE, Web of Science, EMBASE, PsycINFO, Scopus, CINAHL, CNKI, CBM, Weipu and WanFang databases were searched from 1 January 1998 to 30 February 2022. REVIEW METHODS: Following the PRISMA statement recommendations, review methods resulted in 31 quantitative studies retained for inclusion which were evaluated with the evaluation criteria for observational studies as recommended by the Agency for Healthcare Research and Quality. The data were pooled and a random-effects meta-analysis conducted. RESULTS: Findings showed the pooled mental workload score was 65.24, and the pooled prevalence of high mental workload was 54%. Subgroup analysis indicated nurses in developing countries and emergency departments experienced higher mental workloads, and the mental workloads of front-line nurses increased significantly during the COVID-19 pandemic. CONCLUSION: These findings highlight that nurses experience high mental workloads as assessed using the NASA-TLX tool and there is an urgent need to explore interventions to decrease their mental workloads.

Psychological capital among clinical nurses: A latent profile analysis.

AIM: To determine the psychological capital level of nurses and explore the latent profiles of nurses regarding their psychological capital scores. BACKGROUND: The use of individual-centered analysis for the connotation of nurses' psychological capital structure is less studied and still needs to be further explored. METHODS: By the convenience sampling method, 494 clinical nurses from 7 general hospitals in Sichuan province were selected. The study was conducted from December 2022 to February 2023. Latent profile analysis was used for data analysis. We followed STROBE guidelines in this research. RESULTS: The total mean score of nurses' psychological capital is 5.17 (SD = 0.8). The following four latent profiles were identified: "poor" (4.5%), "medium" (22.9%), "well-off" (41.5%), and "rich" (31.1%). Multiple logistic regression showed that the number of hours worked per day and the number of night shifts per month were negative predictors of psychological capital, and psychological training and job satisfaction were protective factors of psychological capital. DISCUSSION: Our study found that the four profiles can be distinguished by "poor," "well-off," "medium," and "rich" levels of psychological capital. Among them, more than 70% of the nurses belonged to the well-off and rich profiles, and the number of the poor profile was the lowest. CONCLUSION: The overall psychological capital of clinical nurses is at a medium-high level. Each profile is influenced by multiple sociodemographic factors (i.e., age, working hours, monthly income, psychological training, and job satisfaction). IMPLICATIONS FOR NURSING AND HEALTH POLICY: Administrators should develop enhancement strategies to improve the mental health of nurses based on the characteristics of their psychological capital profiles.

Levels of psychological capital among nurses: A systematic review and meta-analysis.

AIM: To systematically evaluate the available literature about overall levels of psychological capital among nurses. BACKGROUND: Psychological capital is described as a positive mental state associated with nurses' mental health, quality of care and patient outcomes. METHODS: A search was carried out using PubMed, Web of Science, EMBASE, CINAHL, PsycINFO, Cochrane Library and Chinese Database, including China National Knowledge Infrastructure (CNKI), Chinese Biological Medical (CBM), WanFang and Weipu Database from the inception of the databases until October 2021. Subsequently, two researchers identified and reviewed the literature and assessed the risk of bias. A random-effects model was conducted to achieve pooled estimates of psychological capital scales. RESULTS: The pooled mean score of the psychological capital scale was 4.21 (95% CI, 4.07-4.35). For subdimensions such as hope, optimism, self-efficacy and resilience, the score was 4.12 (95% CI, 4.11-4.12), 4.34 (95% CI, 4.34-4.34), 4.50 (95% CI, 4.50-4.51) and 4.34 (95% CI, 4.33-4.34), respectively. Subgroup analyses indicated that nurses practising in Asia and intensive care units might have experienced lower psychological capital levels. In addition, significant differences were noted in studies with sample size and publication year. Studies with a large sample size reported a higher psychological capital than those with a small sample size. The pooled mean scores of psychological capital were higher in 2014-2018 than in 2019-2021. Meta-regression further revealed that geographic regions of participants might be a source of heterogeneity, and the Asian region had 32.23% of the heterogeneity between studies, and the African region had 18.71%. CONCLUSION: This review is the first to synthesize published research and calculate a pooled score of psychological capital in nurses. These findings indicated that nurses reported a medium-high level of psychological capital, and there was significant heterogeneity. IMPLICATIONS FOR NURSING POLICY: Administrators and policymakers should concentrate on nurses' psychological capital and tactically integrate psychological capital into nursing vocational training programs.

A cross sectional study of the impact of psychological capital on organisational citizenship behaviour among nurses: Mediating effect of work engagement.

AIMS: To examine relationships between psychological capital, work engagement and organisational citizenship behaviour among nurses. BACKGROUND: Psychological capital, work engagement and organisational citizenship behaviour are all positive variables associated with work. Clarifying the relationship between the variables can help nursing managers implement tailored and effective intervention strategies to improve individual and organisational performance and quality of care. DESIGN: A quantitative cross-sectional study was designed. METHODS: The study was carried out from June 2021 to September 2021 in Sichuan Province, China. A total of 606 nurses working at six tertiary hospitals were selected with convenience sampling. Participants were investigated using demographic, work-related information questionnaire, Psychological Capital Questionnaire, Utrecht Work Engagement Scale and Organizational Citizenship Behavior Questionnaire. RESULTS: The scores of psychological capital, work engagement and organisational citizenship behaviour were 102.56 ± 15.47, 67.96 ± 21.71 and 101.57 ± 11.57, respectively. The multiple linear regression model explained 7.3% of the total variance in organisational citizenship behaviour related to demographic and work-related factors. There was a significant positive correlation between psychological capital, work engagement and nurses' organisational citizenship behaviour. Additionally, structural equation modeling showed that work engagement mediated the relationship between psychological capital and organisational citizenship behaviour with the partial mediating effect of 0.093. The final model explained 28% of organisational citizenship behaviour. CONCLUSION: Our results suggest that both psychological capital and work engagement are facilitators for organisational citizenship behaviour in nurses. Managers can increase nurses' organisational citizenship behaviour through developing psychological capital and improving the work engagement. IMPLICATIONS FOR NURSING MANAGEMENT: This study indicates that both psychological capital and work engagement are protective factors of organisational citizenship behaviour, which provide proof for optimizing human resources management from a positive psychology perspective. Our finding can help managers correctly understand the mechanism of the relationship among work engagement, psychological capital and organisational citizenship behaviour and adopt effective intervention strategies to promote nurses' organisational citizenship behaviour.

Psychological Symptoms and Posttraumatic Growth Among the General Population in Wuhan, China During the COVID-19 Pandemic: A Cross-Sectional Study.

The aim of the current study was to investigate psychological symptoms and post-traumatic growth (PTG) among the general population in Wuhan, China during the coronavirus disease 2019 (COVID-19) pandemic. An online survey was conducted using convenience sampling. Participants were invited to fill out this questionnaire, which included information on sociodemographic characteristics and other survey objectives. The Psychological Questionnaire for Emergent Events of Public Health (PQEEPH) and the Chinese version of the Posttraumatic Growth Inventory (PTGI) were used. The prevalence of depression, neurasthenia, fear, obsessive-anxiety, and hypochondriasis among 311 participants were 61.1%, 69.8%, 97.8%, 57.2%, and 45%, respectively. Results indicated that a substantial proportion of the general population may have experienced psychological symptoms as well as PTG, due to the COVID-19 pandemic. Findings demonstrate the importance of developing targeted psychological interventions for those at risk for mental health symptoms. [Journal of Psychosocial Nursing and Mental Health Services, 60(4), 39-46.].

Isoindolinone compounds active as Kv1.5 blockers identified using a multicomponent reaction approach.

A series of isoindolinone compounds have been developed showing good in vitro potency on the Kv1.5 ion channel. By modification of two side chains on the isoindolinone scaffold, metabolically stable compounds with good in vivo PK profile could be obtained leaving the core structure unsubstituted. In this way, low microsomal intrinsic clearance (CLint) could be achieved despite a relatively high logD. The compounds were synthesized using the Ugi reaction, in some cases followed by Suzuki and Diels-Alder reactions, giving a diverse set of compounds in a small number of reaction steps.

Lactam sulfonamides as potent inhibitors of the Kv1.5 potassium ion channel.

A series of lactam sulfonamides has been discovered and optimized as inhibitors of the Kv1.5 potassium ion channel for treatment of atrial fibrillation. In vitro structure-activity relationships from lead structure C to optimized structure 3y are described. Compound 3y was evaluated in a rabbit PD-model and was found to selectively prolong the atrial effective refractory period at submicromolar concentrations.

Rumination, psychological capital and academic procrastination among nursing students: A cross-sectional study.

BACKGROUND: Academic procrastination is common among college students, which affects their learning status and even their physical and mental health. Rumination, psychological capital, and academic procrastination are closely related, but for nursing students, there are few studies reporting on their levels and relationships. OBJECTIVE: The aim of this study was to investigate the levels of rumination, psychological capital, and academic procrastination among nursing students, and examine the mediating role of psychological capital in rumination and academic procrastination. DESIGN: A cross-sectional study. SETTING: The study sampled three medical colleges in Sichuan Province, China. PARTICIPANTS: A convenience sampling method was used to select 556 nursing students from April to June 2023. METHODS: 556 nursing students were asked to complete questionnaires regarding social-demographic information, rumination, psychological capital, and academic procrastination. Descriptive statistics, Pearson correlation analysis and structural equation model were used in this study. RESULTS: The scores of rumination, psychological capital, and academic procrastination among nursing students were 46.08 ± 13.61, 108.28 ± 19.50 and 55.32 ± 12.30, respectively. Additionally, structural equation modeling showed that psychological capital mediated the relationship between rumination and academic procrastination with the partial mediating effect of 0.425. CONCLUSION: Our results suggest that nursing students exhibit moderate levels of rumination, psychological capital and academic procrastination. Moreover, rumination can not only directly affect academic procrastination, but also indirectly through psychological capital. Nursing educators should strengthen their attention to the mental health and learning status of nursing students, take measures to help them adapt to campus life, alleviate rumination, enrich psychological capital, and reduce the risk of academic procrastination.

Investigating the complex relationship and influencing factors of frailty on nutritional status in maintenance hemodialysis patients.

INTRODUCTION: Given the high prevalence and significant challenges of frailty, a state of increased vulnerability to adverse health outcomes, among maintenance hemodialysis (MHD) patients, this cross-sectional study aimed to investigate its prevalence and explore its association with nutritional status and other relevant factors. METHODS: The study involved 290 MHD patients with an average age of 52.98 ± 13.65 years. Frailty assessments, nutritional evaluations, and medical status measurements were performed. Data analysis involved descriptive statistics, correlation analyses, and multivariate logistic regression. RESULTS: Among the patients, 70.3% were identified with frailty (16.9% frail, 53.4% pre-frail). Frailty was more prevalent in female patients compared to males and correlated positively with age, marital status, caregiving needs, comorbidities, dialysis duration, and higher nutritional risk scores. Negative correlations were observed with serum albumin, hemoglobin, body weight, and height. CONCLUSION: A significant prevalence of frailty was found in MHD patients, with notable associations to various demographic, clinical, and nutritional factors.

Influencing factors associated with mental workload among nurses: A latent profile analysis.

Objective: This study aimed to examine the latent profile of nurses' mental workload (MWL) and explore the influencing factors via a person-centred approach. Methods: From March to July 2023, a quantitative cross-sectional study was carried out to investigate 526 Chinese clinical nurses from five tertiary hospitals in Sichuan Province, China, by using demographic information, the Perceived Social Support Scale, Simplified Coping Skill Questionnaire, and NASA-Task Load Index. Latent profile analyses were performed using Mplus 7.3 software. Pearson's chi-squared and logistic regression analysis was done using SPSS 24.0 software. Results: Three profiles of mental workload were identified based on the nurses' responses to the mental workload assessment, designated as "low MWL-high self-rated (n = 70, 13.3%)", "moderate MWL (n = 273, 51.9%)", and "high MWL-low self-rated (n = 183, 34.8%)". Based on the analysis of the three subtypes, nurses with working years < 5 years (χ 2  = 12.135, P < 0.05), no children (χ 2  = 16.182, P < 0.01), monthly income < 6000 (χ 2  = 55.231, P < 0.001), poor health status (χ 2  = 39.658, P < 0.001), no psychological training in the past year (χ2 = 56.329, P < 0.001) and suffering from workplace violence (χ 2  = 19.803, P < 0.001) were significantly associated with MWL. Moreover, the multivariate logistic regression analysis showed that negative coping styles (OR = 1.146, 95% CI: 1.060-1.238, P = 0.001) were accompanied by higher MWL while negatively associated with perceived social support (OR = 0.927, 95% CI: 0.900-0.955, P < 0.001). Conclusion: Our results showed that the MWL of nurses could be classified into three subtypes. Monthly income, health status, psychological training, workplace violence, negative coping style, and perceived social support were the factors influencing MWL. Managers can employ personalised intervention strategies according to the individual characteristics of different subgroups to reduce nurses' MWL.

Identification and design of a novel series of MGAT2 inhibitors.

[Acyl CoA]monoacylglycerol acyltransferase 2 (MGAT2) is of interest as a target for therapeutic treatment of diabetes, obesity and other diseases which together constitute the metabolic syndrome. In this Letter we report our discovery and optimisation of a novel series of MGAT2 inhibitors. The development of the SAR of the series and a detailed discussion around some key parameters monitored and addressed during the lead generation phase will be given. The in vivo results from an oral lipid tolerance test (OLTT) using the MGAT2 inhibitor (S)-10, shows a significant reduction (68% inhibition relative to naїve, p<0.01) in plasma triacylglycerol (TAG) concentration.

Discovery of 4-morpholino-pyrimidin-6-one and 4-morpholino-pyrimidin-2-one-containing Phosphoinositide 3-kinase (PI3K) p110ß isoform inhibitors through structure-based fragment optimisation.

The discovery of 4-morpholino-pyrimidin-6-one and 4-morpholino-pyrimidin-2-one-containing inhibitors of Phosphoinositide 3-kinases (PI3K) p110ß isoform is reported. Structure-based optimisation of the original fragment hit resulted in lead compounds with improvements in ligand efficiency, lipophilicity efficiency, p110ß potency and selectivity over p110α.

Discovery of phosphoinositide 3-kinases (PI3K) p110ß isoform inhibitor 4-[2-hydroxyethyl(1-naphthylmethyl)amino]-6-[(2S)-2-methylmorpholin-4-yl]-1H-pyrimidin-2-one, an effective antithrombotic agent without associated bleeding and insulin resistance.

Structure-based evolution of the original fragment leads resulted in the identification of 4-[2-hydroxyethyl(1-naphthylmethyl)amino]-6-[(2S)-2-methylmorpholin-4-yl]-1H-pyrimidin-2-one, (S)-21, a potent, selective phosphoinositide 3-kinases (PI3K) p110ß isoform inhibitor with favourable in vivo antiplatelet effect. Despite its antiplatelet action, (S)-21 did not significantly increase bleeding time in dogs. Additionally, due to its enhanced selectivity over p110α, (S)-21 did not induce any insulin resistance in rats.

Prevalence and factors of compassion fatigue among nurse in China: A protocol for systematic review and meta-analysis.

BACKGROUND: Compassion fatigue is defined as a detrimental consequence of experiencing work-related stress among nurses, which can affect the job performance and harm emotional and physical health. The high risk of compassion fatigue among nurses may be even more severe in China. Although several studies have explored the prevalence and factors of compassion fatigue among Chinese nurses, most data derived merely from the specialty units of the hospital or limited samples, and there is a large heterogeneity among studies. Thus, it is indispensable to systematically summarize the risk factors and prevalence of compassion fatigue among clinical nurse in China. METHODS: Two reviewers will independently conduct comprehensively searches in 9 electronic databases including PubMed, The Cochrane Library, Cumulative Index to Nursing and Allied Health Literature (CINAHL), EMBASE, Web of science, MEDLINE, China National Knowledge Infrastructure (CNKI), WanFang and Chinese Biological Medical Database (CBM) with no search date restriction. Cross-sectional and prospective cohort studies that described the prevalence and factors of Chinese nurses compassion fatigue will be eligible for inclusion. The risk of bias and methodological quality of individual study will be assessed using an adapted quality assessment tool from the Agency for Healthcare Research and Quality (AHRQ). Stata 16.0 software will be used for meta-analysis. RESULTS: The primary outcome will be the prevalence of 3 dimension of compassion fatigue in Chinese nurses. The secondary outcomes will be comparisons of compassion fatigue scores among Chinese nurse of different education background, marital status, employment forms and professional titles. CONCLUSION: This overview will contribute to reveal the prevalence and influencing factors in compassion fatigue among Chinese nurses and provide a scientific evidence for the prediction and prevention in compassion fatigue. REGISTRATION NUMBER: The registration DOI is 10.17605/OSF.IO/V34X6.

Novel Chemical Series of 5-Lipoxygenase-Activating Protein Inhibitors for Treatment of Coronary Artery Disease.

5-Lipoxygenase (5-LO)-activating protein (FLAP) inhibitors have proven to attenuate 5-LO pathway activity and leukotriene production in human clinical trials. However, previous clinical candidates have been discontinued and the link between FLAP inhibition and outcome in inflammatory diseases remains to be established. We here describe a novel series of FLAP inhibitors identified from a screen of 10k compounds and the medicinal chemistry strategies undertaken to progress this series. Compound 4i showed good overall properties and a pIC50 hWBfree of 8.1 and an lipophilic ligand efficiency of 5.2. Target engagement for 4i was established in dogs using ex vivo measurement of leukotriene B4 (LTB4) levels in blood with good correlation to in vitro potency. A predicted human dose of 280 mg b.i.d. suggests a wide margin to any identified in vitro off-target effects and sufficient exposure to achieve an 80% reduction of LTB4 levels in humans. Compound 4i is progressed to preclinical in vivo safety studies.

Identification of Mineralocorticoid Receptor Modulators with Low Impact on Electrolyte Homeostasis but Maintained Organ Protection.

The mechanism-based risk for hyperkalemia has limited the use of mineralocorticoid receptor antagonists (MRAs) like eplerenone in cardio-renal diseases. Here, we describe the structure and property-driven lead generation and optimization, which resulted in identification of MR modulators ( S)-1 and ( S)-33. Both compounds were partial MRAs but still demonstrated equally efficacious organ protection as eplerenone after 4 weeks of treatment in uni-nephrectomized rats on high-salt diet and aldosterone infusion. Importantly, and in sharp contrast to eplerenone, this was achieved without substantial changes to the urine Na+/K+ ratio after acute treatment in rat, which predicts a reduced risk for hyperkalemia. This work led to selection of ( S)-1 (AZD9977) as the clinical candidate for treating MR-mediated cardio-renal diseases, including chronic kidney disease and heart failure. On the basis of our findings, we propose an empirical model for prediction of compounds with low risk of affecting the urinary Na+/K+ ratio in vivo.