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In the pancreas, ligands of receptor tyrosine kinases (RTKs) are thought to be implicated in the development and function of the islets of Langerhans, which represent the endocrine part of the pancreas. In a previous study, we randomly screened by reverse transcriptase-polymerase chain reaction for RTKs expressed in the embryonic pancreas. One cDNA fragment that was cloned during this screen corresponded to the KIT receptor. The objective of the present study was to analyze the pattern of Kit expression in the pancreas. We demonstrated that Kit is expressed and functional in terms of signal transduction in the insulin-producing cell line INS-1. Indeed, upon treatment with the KIT ligand (KITL), the extracellular signal-regulated protein kinase was phosphorylated, and the expression of early responsive genes was induced. We also demonstrated that Kit mRNAs are present in fetal and adult rat islets. We next used mice that had integrated the lacZ reporter gene into the Kit locus. In these mice, beta-galactosidase (beta-gal) served as a convenient marker for expression of the endogenous Kit gene. Kit was found to be specifically transcribed in beta-cells (insulin-expressing cells), whereas no expression was found in other endocrine cell types or in the exocrine tissue. Interestingly, not all mature beta-cells expressed Kit, indicating that Kit is a marker of a subpopulation of beta-cells. Finally, by following beta-gal expression in the pancreas during fetal life, we found that at E14.5, Kit is expressed in both insulin- and glucagon-expressing cells present at that stage, and also in a specific cell population present in the epithelium that stained negative for endocrine markers. These data suggest that these Kit-positive/endocrine-negative cells could represent a subpopulation of endocrine cell precursors. [ABSTRACT FROM AUTHOR]

Background: The 2017 American College of Cardiology/American Heart Association blood pressure guideline recommends initiation of antihypertensive medication for adults with stage 1 hypertension (systolic blood pressure, 130-139 mm Hg, or diastolic blood pressure, 80-89 mm Hg) and 10-year atherosclerotic cardiovascular disease (ASCVD) risk ≥10% estimated by the pooled cohort equations (PCEs). In 2023, the American Heart Association published the predicting risk of cardiovascular disease events (PREVENT) equations to estimate ASCVD and total cardiovascular disease risk., Methods: We analyzed US National Health and Nutrition Examination Survey data from 2013 to 2020 for 1703 adults aged 30 to 79 years without self-reported cardiovascular disease with stage 1 hypertension. We estimated 10-year ASCVD risk by the PCEs and 10-year ASCVD and total cardiovascular disease risk by the base PREVENT equations. Analyses were weighted to represent noninstitutionalized US adults with stage 1 hypertension., Results: Mean 10-year ASCVD risk was 5.4% (95% CI, 5.0%-5.9%) and 2.9% (95% CI, 2.7%-3.1%) using the PCEs and PREVENT equations, respectively. The proportion with 10-year ASCVD risk of 10% to <15% and ≥15% was 8.1% and 7.8% estimated by the PCEs, respectively, and 3.0% and 0.3% estimated by the PREVENT equations, respectively. No participants had a 10-year ASCVD risk ≥10% on the PREVENT equations and <10% on the PCEs, while 12.5% had a 10-year ASCVD risk ≥10% on the PCEs and <10% on the PREVENT equations. The mean 10-year total cardiovascular disease risk estimated by the PREVENT equations was lower than the mean 10-year ASCVD risk on the PCEs., Conclusions: Among US adults with stage 1 hypertension, the 10-year predicted ASCVD risk estimated by the PREVENT equations was approximately half the risk estimated by the PCEs., Competing Interests: M.M. Safford is the founder of MedExplain, a patient education company.

Over the past 3 decades, a substantial body of high-quality evidence has guided the diagnosis and management of elevated blood pressure (BP) in the outpatient setting. In contrast, there is a lack of comparable evidence for guiding the management of elevated BP in the acute care setting, resulting in significant practice variation. Throughout this scientific statement, we use the terms acute care and inpatient to refer to care received in the emergency department and after admission to the hospital. Elevated inpatient BP is common and can manifest either as asymptomatic or with signs of new or worsening target-organ damage, a condition referred to as hypertensive emergency. Hypertensive emergency involves acute target-organ damage and should be treated swiftly, usually with intravenous antihypertensive medications, in a closely monitored setting. However, the risk-benefit ratio of initiating or intensifying antihypertensive medications for asymptomatic elevated inpatient BP is less clear. Despite this ambiguity, clinicians prescribe oral or intravenous antihypertensive medications in approximately one-third of cases of asymptomatic elevated inpatient BP. Recent observational studies have suggested potential harms associated with treating asymptomatic elevated inpatient BP, which brings current practice into question. Despite the ubiquity of elevated inpatient BPs, few position papers, guidelines, or consensus statements have focused on improving BP management in the acute care setting. Therefore, this scientific statement aims to synthesize the available evidence, provide suggestions for best practice based on the available evidence, identify evidence-based gaps in managing elevated inpatient BP (asymptomatic and hypertensive emergency), and highlight areas requiring further research.

Background: Integrase strand transfer inhibitors (INSTI) are a commonly used antiretroviral therapy (ART) class in people with human immunodeficiency virus (HIV) and associated with weight gain. We studied the association of INSTI-based ART with systolic and diastolic blood pressure (SBP and DBP)., Methods: We recruited 50 people taking INSTI-based ART and 40 people taking non-INSTI-based ART with HIV and hypertension from the University of Alabama at Birmingham HIV clinic. Office BP was measured unattended using an automated (AOBP) device. Awake, asleep and 24-hour BP were measured through ambulatory BP monitoring. Among participants with SBP ≥130 mmHg or DBP≥80 mmHg on AOBP, sustained hypertension was defined as awake SBP≥130 mmHg or DBP≥80 mmHg., Results: Mean SBP and DBP was higher among participants taking INSTI-based versus non-INSTI-based ART (AOBP-SBP/DBP: 144.7/83.8 versus 135.3/79.3 mmHg; awake-SBP/DBP: 143.2/80.9 versus 133.4/76.3 mmHg; asleep-SBP/DBP: 133.3/72.9 versus 120.3/65.4 mmHg; 24-hour-SBP/DBP: 140.4/78.7 versus 130.0/73.7 mmHg). After multivariable adjustment, AOBP, awake, asleep and 24-hour SBP was 12.5 (95%CI 5.0-20.1), 9.8 (95%CI 3.6-16.0), 10.4 (95%CI 2.0-18.9), and 9.8 (95%CI 4.2-15.4) mmHg higher among those taking INSTI-based versus non-INSTI-based ART, respectively. AOBP, awake, asleep and 24-hour DBP was 7.5 (95%CI 0.3-14.6), 6.1 (95%CI 0.3-11.8), 7.5 (95%CI 1.4-13.6), and 6.1 (95%CI 0.9-11.3) mmHg higher among those taking INSTI-based versus non-INSTI-based ART after multivariable adjustment. All participants had SBP ≥130 mmHg or DBP≥80 mmHg on AOBP and 97.9% and 65.7% of participants taking INSTI-based and non-INSTI-based ART had sustained hypertension, respectively., Conclusion: INSTI-based ART was associated with higher SBP and DBP than non-INSTI-based ART., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Journal of Hypertension, Ltd. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: The prevalence of many chronic conditions has increased among US adults. Many adults with hypertension have other chronic conditions., Methods: We estimated changes in the age-adjusted prevalence of multiple (≥3) chronic conditions, not including hypertension, using data from the National Health and Nutrition Examination Survey, from 1999-2000 to 2017-2020, among US adults with (n = 24,851) and without (n = 24,337 hypertension. Hypertension included systolic blood pressure (BP) ≥130 mm Hg, diastolic BP ≥80 mm Hg, or antihypertensive medication use. We studied 14 chronic conditions: arthritis, asthma, cancer, coronary heart disease, chronic kidney disease, depression, diabetes, dyslipidemia, hepatitis B, hepatitis C, heart failure, lung disease, obesity, and stroke., Results: From 1999-2000 to 2017-2020, the age-adjusted mean number of chronic conditions increased more among US adults with vs. without hypertension (2.2 to 2.8 vs. 1.7 to 2.0; P-interaction <0.001). Also, the age-adjusted prevalence of multiple chronic conditions increased from 39.0% to 52.0% among US adults with hypertension and from 26.0% to 30.0% among US adults without hypertension (P-interaction = 0.022). In 2017-2020, after age, gender, and race/ethnicity adjustment, US adults with hypertension were 1.94 (95% confidence interval: 1.72-2.18) times as likely to have multiple chronic conditions compared to those without hypertension. In 2017-2020, dyslipidemia, obesity, and arthritis were the most common 3 co-occurring chronic conditions among US adults with and without hypertension (age-adjusted prevalence 16.5% and 3.1%, respectively)., Conclusions: In 2017-2020, more than half of US adults with hypertension had ≥3 additional chronic conditions, a substantial increase from 20 years ago., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Journal of Hypertension, Ltd. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Acute kidney injury (AKI) is a serious complication affecting up to 15% of hospitalized patients. Early diagnosis is critical to prevent irreversible kidney damage that could otherwise lead to significant morbidity and mortality. However, AKI is a clinically silent syndrome, and current detection primarily relies on measuring a rise in serum creatinine, an imperfect marker that can be slow to react to developing AKI. Over the past decade, new innovations have emerged in the form of biomarkers and artificial intelligence tools to aid in the early diagnosis and prediction of imminent AKI., Content: This review summarizes and critically evaluates the latest developments in AKI detection and prediction by emerging biomarkers and artificial intelligence. Main guidelines and studies discussed herein include those evaluating clinical utilitiy of alternate filtration markers such as cystatin C and structural injury markers such as neutrophil gelatinase-associated lipocalin and tissue inhibitor of metalloprotease 2 with insulin-like growth factor binding protein 7 and machine learning algorithms for the detection and prediction of AKI in adult and pediatric populations. Recommendations for clinical practices considering the adoption of these new tools are also provided., Summary: The race to detect AKI is heating up. Regulatory approval of select biomarkers for clinical use and the emergence of machine learning algorithms that can predict imminent AKI with high accuracy are all promising developments. But the race is far from being won. Future research focusing on clinical outcome studies that demonstrate the utility and validity of implementing these new tools into clinical practice is needed., (© Association for Diagnostics & Laboratory Medicine 2024. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Introduction: The cardiovascular disease risk reduction benefits of proprotein convertase subtilisin/kexin type 9 inhibitor monoclonal antibodies (PCSK9i mAb) and ezetimibe are dependent on remaining on treatment and being persistent and adherent. We estimated the percentage of patients on therapy, persistent and adherent at 182 and 365 days among US adults with health insurance who initiated a PCSK9i mAb (n = 16,588) or ezetimibe (n = 83,086) between July 2015 and December 2019., Methods: Using pharmacy fill claims, being on therapy was defined as having a day of medication supply in the last 60 of 182 and 365 days following treatment initiation, being persistent was defined as not having a gap of 60 days or more between the last day of supply from one prescription fill and the next fill, and being adherent was defined by having medication available to take on ≥ 80% of the 182 and 365 days following treatment initiation. We estimated multivariable-adjusted risk ratios for being persistent and adherent comparing patients initiating PCSK9i mAb versus ezetimibe using Poisson regression., Results: At 182 days following initiation, 80% and 68% were on therapy and 76% and 64% were persistent among patients who initiated a PCSK9i mAb and ezetimibe, respectively. Among patients who were on therapy and persistent at 182 days following initiation, 88% and 81% of those who initiated a PCSK9i mAb and ezetimibe, respectively, were on therapy at 365 days. Among those on therapy and persistent at 182 days following initiation, being persistent and being adherent at 365 days were each more common among PCSK9i mAb versus ezetimibe initiators (persistent: 82% versus 76%, multivariable-adjusted risk ratio 1.07; 95% confidence interval [CI] 1.06-1.08; adherent: 74% versus 71%, multivariable-adjusted risk ratio 1.02; 95% CI 1.01-1.03)., Conclusions: These data suggest approaches to increase persistence and adherence to PCSK9i mAb and ezetimibe should be implemented prior to or within 182 days following treatment initiation., (© 2024. The Author(s).)

Background: Lipid-lowering therapy (LLT) is underutilized for very high-risk atherosclerotic cardiovascular disease. PROMPT-LIPID (PRagmatic Trial of Messaging to Providers about Treatment of HyperLIPIDemia) sought to determine whether electronic health record (EHR) alerts improve 90-day LLT intensification in patients with very high-risk atherosclerotic cardiovascular disease., Methods: PROMPT-LIPID was a pragmatic trial in which cardiovascular and internal medicine clinicians within Yale New Haven Health (New Haven, CT) were cluster-randomized to receive an EHR alert with individualized LLT recommendations or no alert for outpatients with very high-risk atherosclerotic cardiovascular disease and LDL-C (low-density lipoprotein cholesterol), ≥70 mg/dL. The primary outcome was 90-day LLT intensification (change to high-intensity statin and addition of ezetimibe or PCSK9i [proprotein subtilisin/kexin type 9 inhibitors]). Secondary outcomes included LDL-C level, proportion of patients with LDL-C of <70 or < 55 mg/dL, rate of major adverse cardiovascular events, ED visit incidence, and 6-month mortality. Results were analyzed using logistic and linear regression clustered at the provider level., Results: The no-alert group included 47 clinicians and 1370 patients (median age, 71 years; 50.1% female, median LDL-C, 93 mg/dL); the alert group included 49 clinicians and 1130 patients (median age, 72 years; 47% female, median LDL-C 91, mg/dL). The primary outcome was observed in 14.1% of patients in the alert group as compared with 10.4% in the no-alert group. There were no differences in any secondary outcomes at 6 months. Among 542 patients whose clinicians (n=46) did not dismiss the EHR alert recommendations, LLT intensification was significantly greater (21.2% versus 10.4%, odds ratio, 2.33 [95% CI, 1.48-3.66])., Conclusions: With a real-time, targeted, individualized EHR alert as compared with usual care, the proportion of patients with atherosclerotic cardiovascular disease with LLT intensification was numerically higher but not statistically significant. Among clinicians who did not dismiss the alert, there was a > 2-fold increase in LLT intensification. EHR alerts, coupled with strategies to reduce clinician dismissal, may help address persistent gaps in LDL-C management., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04394715, https://www.clinicaltrials.gov/ct2/show/study/NCT04394715., Competing Interests: Disclosures Dr Desai receives support from the Centers for Medicare and Medicaid Services to develop and maintain performance measures that are used for public reporting and payment programs; receives research support from and provides consulting for Amgen, Astra Zeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Cytokinetics, Novartis, SC Pharmaceuticals, and Vifor; and serves on the medical review committee for Anthem. R.J. Riello is a consultant for Alexion, Amgen, AstraZeneca, Boehringer Ingelheim, Janssen, Johnson & Johnson, PhaseBio, and Portola. The other authors report no conflicts.

Background: Death certificate data indicate that hypertension may have increased as a contributing cause of death among US adults. Hypertension is not commonly recorded on death certificates although it contributes to a substantial proportion of cardiovascular disease (CVD) deaths., Methods: We estimated changes in all-cause, CVD, and non-CVD mortality over 5 years of follow-up among 4 cohorts of US adults with hypertension using mortality follow-up data from National Health and Nutrition Examination Survey III in 1988 to 1994, and National Health and Nutrition Examination Survey cycles from 1999 to 2000 through 2015 to 2016 (n=20 927). Hypertension was defined as systolic blood pressure ≥140 mm Hg, diastolic blood pressure ≥90 mm Hg, or antihypertensive medication use. Participants were grouped according to the date of their National Health and Nutrition Examination Survey study visit (1988-1994, 1999-2004, 2005-2010, 2011-2016)., Results: There were 2646, 1048, and 1598 all-cause, CVD, and non-CVD deaths, respectively. After age, gender, and race/ethnicity adjustment and compared with the 1988 to 1994 cohort, the hazard ratio of all-cause mortality was 0.88 (95% CI, 0.76-1.01) for the 1999 to 2004 cohort, 0.82 (95% CI, 0.70-0.95) for the 2005 to 2010 cohort, and 0.89 (95% CI, 0.75-1.05) for the 2011 to 2016 cohort ( P trend=0.123). The age, gender, and race/ethnicity-adjusted hazard ratios for CVD mortality compared with the 1988 to 1994 cohort were 0.74 (95% CI, 0.60-0.90) for the 1999 to 2004 cohort, 0.61 (95% CI, 0.50-0.74) for the 2005 to 2010 cohort, and 0.57 (95% CI, 0.44-0.74) for the 2011 to 2016 cohort ( P trend <0.001). There was no evidence of a change in CVD mortality between the 2005 to 2010 and 2011 to 2016 cohorts ( P =0.661). Noncardiovascular mortality did not decline over the study period ( P trend=0.145)., Conclusions: The decline in CVD mortality among US adults with hypertension stalled after 2005 to 2010., Competing Interests: Disclosures None.

Background: Less than 50% of non-Hispanic Asian adults taking antihypertensive medication have controlled blood pressure., Methods: We compared non-persistence and low adherence to antihypertensive medication between non-Hispanic Asian and other race/ethnicity groups among US adults ≥66 years who initiated antihypertensive medication between 2011 and 2018 using a 5% random sample of Medicare beneficiaries (non-Hispanic Asian, n = 2,260; non-Hispanic White, n = 56,000; non-Hispanic Black, n = 5,792; Hispanic, n = 4,212; and Other, n = 1,423). Non-persistence was defined as not having antihypertensive medication available to take in the last 90 of 365 days following treatment initiation. Low adherence was defined as having antihypertensive medication available to take on <80% of the 365 days following initiation., Results: In 2011-2012, 2013-2014, 2015-2016 and 2017-2018, the proportion of non-Hispanic Asian Medicare beneficiaries with non-persistence was 29.1%, 25.6%, 25.4% and 26.7% (p-trend = 0.381), respectively, and the proportion with low adherence was 58.1%, 54.2%, 53.4% and 51.6%, respectively (p-trend = 0.020). In 2017-2018, compared with non-Hispanic Asian beneficiaries, non-persistence was less common among non-Hispanic White beneficiaries (risk ratio 0.74 [95%CI, 0.64-0.85]), non-Hispanic Black beneficiaries (0.80 [95%CI 0.68-0.94]) and those reporting Other race/ethnicity (0.68 [95%CI, 0.54-0.85]) but not among Hispanic beneficiaries (1.04 [95%CI, 0.88-1.23]). Compared to non-Hispanic Asian beneficiaries, non-Hispanic White beneficiaries and beneficiaries reporting Other race/ethnicity were less likely to have low adherence to antihypertensive medication (relative risk 0.78 [95%CI 0.72-0.84] and 0.84 [95%CI 0.74-0.95], respectively); there was no association for non-Hispanic Black or Hispanic beneficiaries., Conclusions: Non-persistence and low adherence to antihypertensive medication were more common among older non-Hispanic Asian than non-Hispanic White adults., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Choi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Severe hypertension (sHTN) is prevalent in 10% of hospitalized patients and treatment guidelines are lacking. As such, patients who develop sHTN might unnecessarily receive antihypertensive medications which could lead to worse outcomes. Our goal was to investigate correlates of spontaneous blood pressure (BP) reduction to help guide future treatment decisions and avoid harm associated with aggressive BP treatment., Methods: This is a retrospective cohort study of hospitalized adults between 2016 and 2020 who developed sHTN, SBP >180 or DBP >110 mm Hg, after admission. Spontaneous BP reduction was defined as a SBP <160 and a DBP <100 mm Hg achieved within 3 h of sHTN in the absence of antihypertensive therapy. Multivariable logistic regression was used to identify correlates of spontaneous BP reduction., Results: Of the 12,825 patients who developed sHTN, 44.2% had spontaneous BP reduction. After adjustment, we found that patients most likely to experience a BP drop received steroids before onset of sHTN (Odds ratio [OR]: 1.3 [1.09, 1.56]), had higher potassium levels on admission (OR: 1.2 [1.09, 1.24]) and were more likely to have a history of chronic pulmonary disease (OR: 1.1 [1.01, 1.18]) or cardiac arrythmia (OR: 1.1 [1.01, 1.18]). While numerically different, these differences were not clinically relevant., Conclusions: Our findings indicate that almost half the patients who develop sHTN have spontaneous BP reduction. Conventional clinical and demographic characteristics were not strong predictors of spontaneous BP reduction following sHTN development. More research is needed to confirm our findings and help guide treatment of sHTN., (© The Author(s) 2023. Published by Oxford University Press on behalf of American Journal of Hypertension, Ltd. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Although orthostatic hypotension (OH) has long been recognized as a manifestation of autonomic dysfunction, a growing body of literature has identified OH as a common comorbidity of hypertension. This connection is complex, related to pathophysiology in blood pressure regulation and the manner by which OH is derived as the difference between 2 blood pressure measurements. While traditional therapeutic approaches to OH among patients with neurodegenerative disorders focus on increasing upright blood pressure to prevent cerebral hypoperfusion, the management of OH among patients with hypertension is more nuanced; resting hypertension is itself associated with adverse outcomes among these patients. Although there is substantial evidence that intensive blood pressure treatment does not cause OH in the majority of patients with essential hypertension, some classes of antihypertensive agents may unmask OH in patients with an underlying autonomic impairment. Practical steps to manage OH among adults with hypertension start with (1) a thorough characterization of its patterns, triggers, and cause; (2) review and removal of aggravating factors (often pharmacological agents not related to hypertension treatment); (3) optimization of an antihypertensive regimen; and (4) adoption of a tailored treatment strategy that avoids exacerbating hypertension. These strategies include countermaneuvers and short-acting vasoactive agents (midodrine, droxidopa). Ultimately, further research is needed on the epidemiology of OH, the impact of hypertension treatment on OH, approaches to the screening and diagnosis of OH, and OH treatment among adults with hypertension to improve the care of these patients and their complex blood pressure pathophysiology.

Background: Despite robust evidence and strong guideline recommendations supporting use of mineralocorticoid receptor antagonists (MRAs) to improve outcomes in patients with heart failure with reduced ejection fraction (HFrEF), these medications remain underused in clinical practice., Objectives: The goal is to determine if providing a tailored best practice alert (BPA) to outpatient providers suggesting guideline-recommended MRAs or information about available hyperkalemia treatment, if present, for patients with HFrEF will increase short-term MRA prescriptions., Methods: PROMPT-MRA (Pragmatic Trial of Messaging to Providers About Treatment With Mineralocorticoid Receptor Antagonists) is a pragmatic, cluster-randomized, controlled study. A total of 119 providers were randomized to receive a BPA or usual care. During an outpatient visit with participating providers, the BPA displayed recent laboratory test values and ejection fraction. The alert suggested guideline-recommended MRAs for eligible patients with a serum potassium of <5.0 mEq/L or novel potassium binders for those with a serum potassium of ≥5.0 mEq/L, each linked to an order set containing the corresponding medication and laboratory monitoring., Results: PROMPT-MRA completed enrollment with 1,210 patients. The primary outcome of PROMPT-MRA is to determine if a tailored BPA for outpatients with HFrEF will lead to higher MRA prescriptions 6 months following randomization compared with usual care. Secondary outcomes included incidence of hyperkalemia, use of novel potassium binders, heart failure hospitalizations, and mortality., Conclusions: If effective, the BPA can be scaled to improve population health outcomes with increased MRA prescribing among eligible patients with HFrEF, with or without a history of hyperkalemia. (Pragmatic Trial of Alerts for Use of Mineralocorticoid Receptor Antagonists [PROMPT-MRA]; NCT04903717)., Competing Interests: Funding Support and Author Disclosures PROMPT-MRA (Pragmatic Trial of Alerts for Use of Mineralocorticoid Receptor Antagonists; NCT04903717) was supported by CSL Vifor. Dr Riello has participated on Advisory Boards for Amgen, AstraZeneca, Boehringer Ingelheim, Janssen, Johnson and Johnson, Medicure, PhaseBio, Portola, and Salix; honoraria and consulting fees from Alexion, Amgen, AstraZeneca, Boehringer Ingelheim, Janssen, Johnson and Johnson, Pfizer, Portola, and Salix; and stock ownership in Akebia Therapeutics, Cytokinetics, Emergent BioSolutions, Iterum, Olema Pharmaceuticals, PhaseBio, and Verve Therapeutics. Dr Ahmad has received consulting fees from Sanofi, Amgen, and Cytokinetics; and has received research funding from Boehringer Ingelheim, AstraZeneca, Cytokinetics, and Relypsa. Dr Wilson has received grants R01DK11391, R01HS027626, and P30DK079310 and research support from AstraZeneca, CSL Vifor, and WHOOP. Dr Desai has worked under contract with the Centers for Medicare and Medicaid Services to develop and maintain performance measures used for public reporting and pay for performance programs; and has received research grants from and consulted for Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Cytokinetics, Novartis, SCPharmaceuticals, and CSL Vifor. Drs Wilson and Desai are primary investigators of the ongoing PROMPT-MRA funded by CSL Vifor. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024. Published by Elsevier Inc.)

Background: Orthostatic changes in blood pressure (BP), either orthostatic hypotension or orthostatic hypertension (OHTN), are common among patients with chronic kidney disease. Whether they are associated with unique out-of-office BP phenotypes is unknown., Methods: CRIC is a prospective, multicenter, observational cohort study of participants with CKD. BP measured at 2 min after standing and ambulatory BP monitoring (ABPM) were obtained on 1386 participants. Orthostatic hypotension was defined as a 20 mmHg drop in SBP or 10 mmHg drop in DBP when changing from seated to standing positions. Systolic and diastolic night-to-day ratio was also calculated. OHTN was defined as a 20 or 10 mmHg rise in SBP or DBP when changing from a seated to a standing position. White-coat effect (WCE) was defined as seated minus daytime ambulatory BP., Results: Of the 1386 participants (age: 58 ± 10 years, 44% female, 39% black), 68 had orthostatic hypotension and 153 had OHTN. Postural reduction in SBP or DBP was positively associated with greater systolic and diastolic WCE and systolic and diastolic night-to-day ratio. Orthostatic hypotension was positively associated with diastolic WCE (β = 3 [0.2, 5.9]). Diastolic OHTN was negatively associated with systolic WCE (β = -4 [-7.2, -0.5]) and diastolic WCE (β = -6 [-8.1, -4.2])., Conclusion: Postural change in BP was associated with WCE and night-to-day-ratio. Orthostatic hypotension was positively associated with WCE and OHTN was negatively associated with WCE. These findings strengthen observations that postural changes in BP may associate with distinct BP patterns throughout the day. These observations are informative for subsequent research tailoring orthostatic hypotension and OHTN treatment to specific BP phenotypes., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Having chronic conditions may result in reduced physical and cognitive function but less is known about multimorbidity with daily movement. We examined the association of multimorbidity and device-measured total daily movement in a nationally representative sample of US adults aged ≥ 30 years from the 2011-2014 National Health and Nutrition Examination Surveys., Methods: Any multimorbidity (≥2 conditions) and complex multimorbidity (≥3 conditions across ≥ 3 body systems) were quantified using 16 chronic conditions via self-report and/or clinical thresholds. Total movement over 24-hours (Monitor-Independent Movement Summary units [MIMS-units]) was measured using a wrist-worn device (ActiGraph GT3X). Multivariable linear regression examined the association of 1) each chronic condition, 2) number of conditions, 3) any multimorbidity, and 4) complex multimorbidity with total movement. Covariates included age, gender, race/ethnicity, educational attainment, and smoking status., Results: Among US adults (N = 7304, mean age: 53.2 ± 0.34 years, 53.2% female, 69.4% Non-Hispanic White), 62.2% had any multimorbidity with 34.2% having complex multimorbidity. After adjustment, a higher number of chronic conditions was associated with incrementally lower total movement (β MIMS-units [95% CI] compared to those with no chronic conditions; one: -419 [-772, -66], two: -605 [-933, -278], three: -1201 [-1506, -895], four: -1908 [-2351, -1465], 5+: -2972 [-3384, -2560]). Complex multimorbidity presence was associated with -1709 (95% CI: -2062, -1357) and -1269 (-1620, -918) lower total movement compared to those without multimorbidity and multimorbidity but not complex, respectively., Conclusions: Multimorbidity was associated with lower 24-h movement among US adults and may be helpful for identifying adults at risk for low movement., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors. Published by Elsevier Inc.)

Background and Aims: Patients hospitalized for acute heart failure (AHF) continue to be discharged on an inadequate number of guideline-directed medical therapies (GDMT) despite evidence that inpatient initiation is beneficial. This study aimed to examine whether a tailored electronic health record (EHR) alert increased rates of GDMT prescription at discharge in eligible patients hospitalized for AHF., Methods: Pragmatic trial of messaging to providers about treatment of acute heart failure (PROMPT-AHF) was a pragmatic, multicenter, EHR-based, and randomized clinical trial. Patients were automatically enrolled 48 h after admission if they met pre-specified criteria for an AHF hospitalization. Providers of patients in the intervention arm received an alert during order entry with relevant patient characteristics along with individualized GDMT recommendations with links to an order set. The primary outcome was an increase in the number of GDMT prescriptions at discharge., Results: Thousand and twelve patients were enrolled between May 2021 and November 2022. The median age was 74 years; 26% were female, and 24% were Black. At the time of the alert, 85% of patients were on β-blockers, 55% on angiotensin-converting enzyme inhibitor/angiotensin receptor blocker/angiotensin receptor-neprilysin inhibitor, 20% on mineralocorticoid receptor antagonist (MRA) and 17% on sodium-glucose cotransporter 2 inhibitor. The primary outcome occurred in 34% of both the alert and no alert groups [adjusted risk ratio (RR): 0.95 (0.81, 1.12), P = .99]. Patients randomized to the alert arm were more likely to have an increase in MRA [adjusted RR: 1.54 (1.10, 2.16), P = .01]. At the time of discharge, 11.2% of patients were on all four pillars of GDMT., Conclusions: A real-time, targeted, and tailored EHR-based alert system for AHF did not lead to a higher number of overall GDMT prescriptions at discharge. Further refinement and improvement of such alerts and changes to clinician incentives are needed to overcome barriers to the implementation of GDMT during hospitalizations for AHF. GDMT remains suboptimal in this setting, with only one in nine patients being discharged on a comprehensive evidence-based regimen for heart failure., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background & Aims: Obstructive sleep apnoea (OSA) and obesity share a complex bi-directional relationship as location of body fat and changes in regional body composition may be more important for OSA improvement than changes in total body weight only. The aim of this study was to evaluate the impact of a 6-month weight loss intervention for adults newly diagnosed with moderate-severe OSA and obesity on regional body composition. The secondary aims evaluated the relationship between changes in OSA symptoms and severity and anthropometry and regional body composition during the first 12-months after commencing CPAP and explored differences in outcomes between males and females., Methods: Participants (n = 59) received CPAP overnight at home alongside a 6-month modified fasting intervention with 12-months follow up. Regional body composition was measured by Dual X-ray absorptiometry, (DXA) and anthropometry before and after the lifestyle intervention. OSA severity was measured using the apnoea hypopnea index via overnight polysomnography and OSA symptoms were measured using the Epworth Sleepiness scale., Results: Forty-seven adults (74% male) had complete measures available with a mean age of 50.0 y (SD 11.0) and BMI 34.1 kg/m 2 (SD 5.0). Following the intervention average fat mass changed by -5.27 kg (5.36), p < 0.001) and visceral adipose tissue (-0.63 kg (0.67), p < 0.001) significantly decreased in males only with a maintenance of fat-free mass (mean -0.41 kg (1.80), p = 0.18). Females (n = 12) had significant decreases in waist circumference (mean -3.36 cm (3.18) p < 0.01), android lean (-0.12 kg (0.04), p < 0.05) and android total mass (-0.28 kg (0.39), p < 0.05) only. Regional body composition changes in males were positively associated with improvements in OSA severity (p < 0.01) but not OSA symptoms., Conclusion: Improvements in regional body composition were seen in males only which were related to improvements in OSA severity but not OSA symptoms. Females may exhibit different OSA pathophysiology and may require different treatment approaches., Trial Registration: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=369975&isReview=trueAACTRN12616000203459 ACTRN12616000203459., Competing Interests: Conflict of interest This trial was an investigator-initiated trial. Air Liquide provided CPAP machines and support to participants at no cost and had no role in the trial design and protocol development. By contractual agreement, researchers at Monash University have responsibility and independence regarding data management, analysis and publication. GSH has received equipment to support research from Resmed, Philips Respironics and Air Liquide Healthcare. All other authors declare no other competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The need for diverse representation in clinical trials has recently been reinforced by the Food and Drug Administration's (FDA) guidance for industry entitled, "Diversity Plans to Improve Enrollment of Participants from Underrepresented Racial and Ethnic Populations in Clinical Trials." By ensuring inclusion of underrepresented racial and ethnic minority populations in clinical trials, results can be more generalizable and the safety and efficacy can be accurately assessed within the diverse U.S. population. Limitations exist in the interpretation and implementation of clinical trial results reported using the current racial and ethnic categories, as these standards do not reflect the true diversity of the U.S. population. This is particularly true for the Middle Eastern and North African (MENA) population, which is usually overlooked given the lack of an established category. Although the international MENA region demonstrates the highest prevalence of diabetes in the world at 12.2%, the actual prevalence among MENA individuals living in the U.S. may be "hidden" within the White category. Therefore, data on the MENA population should be disaggregated from data within the White category to not only unmask health disparities, but also to ensure adequate representation in clinical trials. This paper discusses the importance of appropriate representation and inclusion of the MENA population in diabetes clinical trials, which is a critical public health issue domestically and globally., (Copyright © 2023 National Medical Association. Published by Elsevier Inc. All rights reserved.)

The incidence of malnutrition in developing countries, such as Kenya, is still high. The most recent international reports outline an increase in the prevalence of overnutrition in Sub-Saharan Africa, where undernutrition and hidden hunger conditions still represent an emergency. Among the factors influencing malnutrition conditions connected to dietary intake and eating habits, evidence shows the importance of food knowledge. Traditionally, in developing countries, women represent the pillar of the food system and impact their children's nutrition: food-based, women-centred strategies are recommended to address nutrient gaps, educate and empower women, and counteract malnutrition. The short communication presents the results of the ACTION project: an educational-intervention pilot study targeting childbearing-age women living in rural areas of Southern Kenya. To evaluate the feasibility of the educational course built, the authors administered to the women a food knowledge questionnaire, before and after the intervention. Study results describe an increase in women's food knowledge after attending the food education course. This encourages to increase education courses which can represent a starting point in improving food habits with a positive effect on the health condition in developing counties too., (© The Author(s) 2023.)

Introduction: Acute kidney injury requiring renal replacement therapy (AKI-RRT) is common in the intensive care unit (ICU) and is associated with significant morbidity and mortality. Continuous RRT (CRRT) non-selectively removes large amounts of amino acids from plasma, lowering serum amino acid concentrations and potentially depleting total-body amino acid stores. Therefore, the morbidity and mortality associated with AKI-RRT may be partly mediated through accelerated skeletal muscle atrophy and resulting muscle weakness. However, the impact of AKI-RRT on skeletal muscle mass and function during and following critical illness remains unknown. We hypothesise that patients with AKI-RRT have higher degrees of acute muscle loss than patients without AKI-RRT and that AKI-RRT survivors are less likely to recover muscle mass and function when compared with other ICU survivors., Methods and Analysis: This protocol describes a prospective, multicentre, observational trial assessing skeletal muscle size, quality and function in ICU patients with AKI-RRT. We will perform musculoskeletal ultrasound to longitudinally evaluate rectus femoris size and quality at baseline (within 48 hours of CRRT initiation), day 3, day 7 or at ICU discharge, at hospital discharge, and 1-3 months postdischarge. Additional skeletal muscle and physical function tests will be performed at hospital discharge and postdischarge follow-up. We will analyse the effect of AKI-RRT by comparing the findings in enrolled subjects to historical controls of critically ill patients without AKI-RRT using multivariable modelling., Ethics and Dissemination: We anticipate our study will reveal that AKI-RRT is associated with greater degrees of muscle loss and dysfunction along with impaired postdischarge recovery of physical function. These findings could impact the in-hospital and postdischarge treatment plan for these patients to include focused attention on muscle strength and function. We intend to disseminate findings to participants, healthcare professionals, the public and other relevant groups via conference presentation and publication without any publication restrictions., Trial Registration Number: NCT05287204., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Acute kidney injury is common among hospitalized individuals, particularly those exposed to certain medications, and is associated with substantial morbidity and mortality. In a pragmatic, open-label, National Institutes of Health-funded, parallel group randomized controlled trial (clinicaltrials.gov NCT02771977), we investigate whether an automated clinical decision support system affects discontinuation rates of potentially nephrotoxic medications and improves outcomes in patients with AKI. Participants included 5060 hospitalized adults with AKI and an active order for any of three classes of medications of interest: non-steroidal anti-inflammatory drugs, renin-angiotensin-aldosterone system inhibitors, or proton pump inhibitors. Within 24 hours of randomization, a medication of interest was discontinued in 61.1% of the alert group versus 55.9% of the usual care group (relative risk 1.08, 1.04 - 1.14, p = 0.0003). The primary outcome - a composite of progression of acute kidney injury, dialysis, or death within 14 days - occurred in 585 (23.1%) of individuals in the alert group and 639 (25.3%) of patients in the usual care group (RR 0.92, 0.83 - 1.01, p = 0.09). Trial Registration Clinicaltrials.gov NCT02771977., (© 2023. The Author(s).)

Background Although hypertensive blood pressure measurements are common in hospitalized children, the degree of inpatient hypertension and blood pressure variability (BPV) associated with end organ complications like acute kidney injury (AKI) is unknown. Methods and Results All analyses are based on a retrospective cohort of children aged 1 to 17 years with ≥2 creatinine measurements during admission from 2014 to 2018. We used time-updated Cox models to evaluate the association between BPV and hypertension with AKI. Time-varying BPV and hypertension were based on blood pressure in the preceding 72 hours. For the analysis of hypertension and AKI, we excluded patients on vasopressors to ensure comparison between hypertensive and normotensive patients. During 5425 pediatric encounters, 258 430 blood pressure measurements were recorded (median [interquartile range] 22 [11-47] readings per encounter). Among all measurements, 32.7% were ≥95th percentile and 18.9% were ≥99th percentile for age, sex, and height. AKI occurred in 389 (7.2%) encounters. We observed a U-shaped relationship between mean blood pressure and incident AKI. BPV was associated with AKI, with the largest effect sizes in the systolic and mean arterial pressure variability measures. Multiple hypertension thresholds were associated with AKI after controlling for confounders. In an additional multivariable model adjusted for BPV, the association between hypertension and AKI was attenuated but remained significant for hypertension defined as three stage 2 measurements in 1 day (hazard ratio, 1.43 [95% CI, 1.01-2.01]). Conclusions Hypertension and BPV are associated with AKI in hospitalized children. Future studies are needed to determine how pharmacologic and nonpharmacologic interventions modify AKI risk in pediatric inpatients with hypertension.

Importance: Intensive vs standard treatment to lower systolic blood pressure (SBP) reduces risk of mild cognitive impairment (MCI) or dementia; however, the magnitude of cognitive benefit likely varies among patients., Objective: To estimate the magnitude of cognitive benefit of intensive vs standard systolic BP (SBP) treatment., Design, Setting, and Participants: In this ad hoc secondary analysis of the Systolic Blood Pressure Intervention Trial (SPRINT), 9361 randomized clinical trial participants 50 years or older with high cardiovascular risk but without a history of diabetes, stroke, or dementia were followed up. The SPRINT trial was conducted between November 1, 2010, and August 31, 2016, and the present analysis was completed on October 31, 2022., Intervention: Systolic blood pressure treatment to an intensive (<120 mm Hg) vs standard (<140 mm Hg) target., Main Outcomes and Measures: The primary outcome was a composite of adjudicated probable dementia or amnestic MCI., Results: A total of 7918 SPRINT participants were included in the analysis; 3989 were in the intensive treatment group (mean [SD] age, 67.9 [9.2] years; 2570 [64.4%] men; 1212 [30.4%] non-Hispanic Black) and 3929 were in the standard treatment group (mean [SD] age, 67.9 [9.4] years; 2570 [65.4%] men; 1249 [31.8%] non-Hispanic Black). Over a median follow-up of 4.13 (IQR, 3.50-5.88) years, there were 765 and 828 primary outcome events in the intensive treatment group and standard treatment group, respectively. Older age (hazard ratio [HR] per 1 SD, 1.87 [95% CI, 1.78-1.96]), Medicare enrollment (HR per 1 SD, 1.42 [95% CI, 1.35-1.49]), and higher baseline serum creatinine level (HR per 1 SD, 1.24 [95% CI, 1.19-1.29]) were associated with higher risk of the primary outcome, while better baseline cognitive functioning (HR per 1 SD, 0.43 [95% CI, 0.41-0.44]) and active employment status (HR per 1 SD, 0.44 [95% CI, 0.42-0.46]) were associated with lower risk of the primary outcome. Risk of the primary outcome by treatment goal was estimated accurately based on similar projected and observed absolute risk differences (C statistic = 0.79). Higher baseline risk for the primary outcome was associated with greater benefit (ie, larger absolute reduction of probable dementia or amnestic MCI) of intensive vs standard treatment across the full range of estimated baseline risk., Conclusions and Relevance: In this secondary analysis of the SPRINT trial, participants with higher baseline projected risk of probable dementia or amnestic MCI gained greater absolute cognitive benefit from intensive vs standard SBP treatment in a monotonic fashion., Trial Registration: ClinicalTrials.gov Identifier: NCT01206062.

Importance: Guidelines recommend that all children and adolescents with hypertension undergo evaluation for secondary causes. Identifying clinical factors associated with secondary hypertension may decrease unnecessary testing for those with primary hypertension., Objective: To determine the utility of the clinical history, physical examination, and 24-hour ambulatory blood pressure monitoring for differentiating primary hypertension from secondary hypertension in children and adolescents (aged ≤21 years)., Data Sources and Study Selection: The databases of MEDLINE, PubMed Central, Embase, Web of Science, and Cochrane Library were searched from inception to January 2022 without language limits. Two authors identified studies describing clinical characteristics in children and adolescents with primary and secondary hypertension., Data Extraction and Synthesis: For each clinical finding in each study, a 2 × 2 table was created that included the number of patients with and without the finding who had primary vs secondary hypertension. Risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies tool., Main Outcomes and Measures: Random-effects modeling was used to calculate sensitivity, specificity, and likelihood ratios (LRs)., Results: Of 3254 unique titles and abstracts screened, 30 studies met inclusion criteria for the meta-analysis and 23 (N = 4210 children and adolescents) were used for pooling in the meta-analysis. In the 3 studies conducted at primary care clinics or school-based screening clinics, the prevalence of secondary hypertension was 9.0% (95% CI, 4.5%-15.0%). In the 20 studies conducted at subspecialty clinics, the prevalence of secondary hypertension was 44% (95% CI, 36%-53%). The demographic findings most strongly associated with secondary hypertension were family history of secondary hypertension (sensitivity, 0.46; specificity, 0.90; LR, 4.7 [95% CI, 2.9-7.6]), weight in the 10th percentile or lower for age and sex (sensitivity, 0.27; specificity, 0.94; LR, 4.5 [95% CI, 1.2-18]), history of prematurity (sensitivity range, 0.17-0.33; specificity range, 0.86-0.94; LR range, 2.3-2.8), and age of 6 years or younger (sensitivity range, 0.25-0.36; specificity range, 0.86-0.88; LR range, 2.2-2.6). Laboratory studies most associated with secondary hypertension were microalbuminuria (sensitivity, 0.13; specificity, 0.99; LR, 13 [95% CI, 3.1-53]) and serum uric acid concentration of 5.5 mg/dL or lower (sensitivity range, 0.70-0.73; specificity range, 0.65-0.89; LR range, 2.1-6.3). Increased daytime diastolic blood pressure load combined with increased nocturnal systolic blood pressure load on 24-hour ambulatory blood pressure monitoring was associated with secondary hypertension (sensitivity, 0.40; specificity, 0.82; LR, 4.8 [95% CI, 1.2-20]). Findings associated with a decreased likelihood of secondary hypertension were asymptomatic presentation (LR range, 0.19-0.36), obesity (LR, 0.34 [95% CI, 0.13-0.90]), and family history of any hypertension (LR, 0.42 [95% CI, 0.30-0.57]). Hypertension stage, headache, and left ventricular hypertrophy did not distinguish secondary from primary hypertension., Conclusions and Relevance: Family history of secondary hypertension, younger age, lower body weight, and increased blood pressure load using 24-hour ambulatory blood pressure monitoring were associated with a higher likelihood of secondary hypertension. No individual sign or symptom definitively differentiates secondary hypertension from primary hypertension.

Acute Heart failure (AHF) is among the most frequent causes of hospitalization in the United States, contributing to substantial health care costs, morbidity, and mortality. Inpatient initiation of guideline-directed medical therapy (GDMT) is recommended for patients with heart failure with reduced ejection fraction (HFrEF) to reduce the risk of cardiovascular death or HF hospitalization. However, underutilization of GDMT prior to discharge is pervasive, representing a valuable missed opportunity to optimize evidence-based care. The PRagmatic Trial Of Messaging to Providers about Treatment of Acute Heart Failure tests the effectiveness of an electronic health record embedded clinical decision support system that informs providers during hospital management about indicated but not yet prescribed GDMT for eligible AHF patients with HFrEF. PRagmatic Trial Of Messaging to Providers about Treatment of Acute Heart Failureis an open-label, multicenter, pragmatic randomized controlled trial of 1,012 patients hospitalized with HFrEF. Eligible patients randomized to the intervention group are exposed to a tailored best practice advisory embedded within the electronic health record that alerts providers to prescribe omitted GDMT. The primary outcome is an increase in the proportion of additional GDMT medication classes prescribed at the time of discharge compared to those in the usual care arm., Competing Interests: Disclosures JH, TO, JM are employees of AstraZeneca. RJR is a consultant for Alexion, Amgen, AstraZeneca, Boehringer Ingelheim, Janssen, Johnson & Johnson, PhaseBio, and Portola. RD does executive teaching for Sanofi Consumer Health care. SEI has served on clinical trial committees and advisory boards for Boehringer Ingelheim, AstraZeneca, and Novo Nordisk. He has served as a consultant to Merck, Pfizer, Lexicon, vTv Therapeutics, Esperion and Abbott and has delivered lectures supported by Boehringer Ingelheim and AstraZeneca. TA is consultant for Sanofi-Aventis, Amgen, Cytokinetics. He has research funding from Boehringer Ingelheim, AstraZeneca, Cytokinetics, and Relypsa. NRD works under contract with the Centers for Medicare and Medicaid Services to develop and maintain performance measures used for public reporting and pay for performance programs. He reports research grants and consulting for Amgen, Astra Zeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Cytokinetics, Novartis, SCPharmaceuticals, and Vifor. The remaining authors have nothing to disclose., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Treatment of severe inpatient hypertension (HTN) that develops during hospitalization is not informed by guidelines. Intravenous (i.v.) antihypertensives are used to manage severe HTN even in the absence of acute target organ damage; however they may result in unpredictable blood pressure (BP) reduction and cardiovascular events. Our goal was to assess the association between i.v. antihypertensives and clinical outcomes in this population., Methods: This is a multihospital retrospective study of adults admitted for reasons other than HTN who develop severe HTN during hospitalization without acute target end organ damage. We defined severe HTN as BP elevation of systolic >180 or diastolic >110 mmHg. Treatment was defined as receiving i.v. antihypertensives within 3 h of BP elevation. We used overlap propensity score weighted Cox models to study the association between treatment and clinical outcomes during index hospitalization., Results: Of 224 265 unique, nonintensive care unit hospitalizations, 20 383 (9%) developed severe HTN, of which 5% received i.v. antihypertensives and 79% were untreated within 3 h of severe BP elevation. In the overlap propensity weighted population, patients who received i.v. antihypertensives were more likely to develop myocardial injury (5.9% in treated versus 3.6% in untreated; hazard ratio [HR]: 1.6 [1.13, 2.24]). Treatment was not associated with increased risk of stroke (HR: 0.7 [0.3, 1.62]), acute kidney injury (HR: 0.97 [0.81, 1.17]), or death (HR: 0.86 [0.49, 1.51])., Conclusions: Intravenous antihypertensives were associated with increased risk of myocardial injury in patients who develop severe HTN during hospitalization. These results suggest that i.v. antihypertensives should be used with caution in patients without acute target organ damage., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background/objectives: Continuous positive airway pressure (CPAP) concomitant with weight loss is a recommended treatment approach for adults with moderate-severe obstructive sleep apnoea (OSA) and obesity. This requires multiple synchronous behaviour changes. The aim of this study was to examine the effectiveness of a 6-month lifestyle intervention and to determine whether the timing of starting a weight loss attempt affects weight change and trajectory after 12 months in adults newly diagnosed with moderate-severe OSA and treated at home with overnight CPAP., Methods: Using a stepped-wedge design, participants were randomised to commence a six-month lifestyle intervention between one and six-months post-enrolment, with a 12-month overall follow-up. Adults (n = 60, 75% males, mean age 49.4 SD 10.74 years) newly diagnosed with moderate-severe OSA and above a healthy weight (mean BMI 34.1 SD 4.8) were recruited., Results: After 12 months, exposure to the intervention (CPAP and lifestyle) resulted in a 3.7 (95% CI: 2.6 to 4.8, p < 0.001) kg loss of weight compared to the control condition (CPAP alone). Timing of the weight loss attempt made no difference to outcomes at 12 months. When exposed to CPAP only (control period) there was no change in body weight (Coef, [95% CI] 0.03, [-0.3 to 0.36], p = 0.86)., Conclusions: The lifestyle intervention resulted in a modest reduction in body weight, while timing of commencement did not impact the degree of weight loss at 12 months. These findings support the recommendation of adjunctive weight-loss interventions within six-months of starting CPAP., (© 2022. The Author(s).)

Purpose of Review: We reviewed the effects of hypertension and the means to prevent and treat it across the spectrum of a woman's lifespan and identified gaps in sex-specific mechanisms contributing to hypertension in women that need to be addressed., Recent Findings: Hypertension continues to be an important public health problem for women across all life stages from adolescence through pregnancy, menopause, and older age. There remain racial, ethnic, and socioeconomic differences in hypertension rates not only overall but also between the sexes. Blood pressure cutoffs during pregnancy have not been updated to reflect the 2017 ACC/AHA changes due to a lack of data. Additionally, the mechanisms behind hypertension development in menopause, including sex hormones and genetic factors, are not well understood. In the setting of increasing inactivity and obesity, along with an aging population, hypertension rates are increasing in women. Screening and management of hypertension throughout a women's lifespan are necessary to reduce the burden of cardiovascular disease, and further research to understand sex-specific hypertension mechanisms is needed., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Despite guideline recommendations to optimize low-density lipoprotein cholesterol (LDL-C) reduction with intensification of lipid-lowering therapy (LLT) in patients with atherosclerotic cardiovascular disease (ASCVD), few of these patients achieve LDL-C < 70 mg/dL in practice., Purpose: We developed a real-time, targeted electronic health record (EHR) alert with embedded ordering capability to promote intensification of evidence based LLT in outpatients with very high risk ASCVD., Methods: We designed a pragmatic, multicenter, single-blind, cluster randomized trial to test the effectiveness of an EHR-based LLT intensification alert. The study will enroll about 100 providers who will be randomized to either receive the alert or undergo usual care for outpatients with high risk ASCVD with LDL-C > 70 mg/dL. Total enrollment will include 2,500 patients. The primary outcome will be the proportion of patients with LLT intensification at 90 days. Secondary outcomes include achieved LDL-C at 6 months and the proportion of patients with LDL-C < 70 mg/dL or < 55 mg/dL at 6 months., Results: Enrollment of 1,250 patients (50% of goal) was reached within 47 days (50% women, mean age 72, median LDL-C 91). At baseline, 71%, 9%, and 3% were on statins, ezetimibe, or proprotein convertase subtilisin/kexin type 9 inhibitors, respectively., Conclusions: PRagmatic Trial of Messaging to Providers about Treatment of HyperLIPIDemia has rapidly reached 50% enrollment of patients with very high risk ASCVD, demonstrating low baseline LLT utilization. This pragmatic, EHR-based trial will determine the effectiveness of a real-time, targeted EHR alert with embedded ordering capability to promote LLT intensification. Findings from this low-cost, widely scalable intervention to improve LDL-C may have important public health implications., Trial Registration: clinicaltrials.gov NCT04394715., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Importance: Heart failure is a major cause of morbidity and mortality worldwide. The use of risk scores has the potential to improve targeted use of interventions by clinicians that improve patient outcomes, but this hypothesis has not been tested in a randomized trial., Objective: To evaluate whether prognostic information in heart failure translates into improved decisions about initiation and intensity of treatment, more appropriate end-of-life care, and a subsequent reduction in rates of hospitalization or death., Design, Setting, and Participants: This was a pragmatic, multicenter, electronic health record-based, randomized clinical trial across the Yale New Haven Health System, comprising small community hospitals and large tertiary care centers. Patients hospitalized for heart failure who had N-terminal pro-brain natriuretic peptide (NT-proBNP) levels of greater than 500 pg/mL and received intravenous diuretics within 24 hours of admission were automatically randomly assigned to the alert (intervention) or usual-care groups., Interventions: The alert group had their risk of 1-year mortality calculated using an algorithm that was derived and validated using similar historic patients in the electronic health record. This estimate, including a categorical risk assessment, was presented to clinicians while they were interacting with a patient's electronic health record., Main Outcomes and Measures: The primary outcome was a composite of 30-day hospital readmissions and all-cause mortality at 1 year., Results: Between November 27, 2019, through March 7, 2021, 3124 patients were randomly assigned to the alert (1590 [50.9%]) or usual-care (1534 [49.1%]) group. The alert group had a median (IQR) age of 76.5 (65-86) years, and 796 were female patients (50.1%). Patients from the following race and ethnicity groups were included: 13 Asian (0.8%), 324 Black (20.4%), 136 Hispanic (8.6%), 1448 non-Hispanic (91.1%), 1126 White (70.8%), 6 other ethnicity (0.4%), and 127 other race (8.0%). The usual-care group had a median (IQR) age of 77 (65-86) years, and 788 were female patients (51.4%). Patients from the following race and ethnicity groups were included: 11 Asian (1.4%), 298 Black (19.4%), 162 Hispanic (10.6%), 1359 non-Hispanic (88.6%), 1077 White (70.2%), 13 other ethnicity (0.9%), and 137 other race (8.9%). Median (IQR) NT-proBNP levels were 3826 (1692-8241) pg/mL in the alert group and 3867 (1663-8917) pg/mL in the usual-care group. A total of 284 patients (17.9%) and 270 patients (17.6%) were admitted to the intensive care unit in the alert and usual-care groups, respectively. A total of 367 patients (23.1%) and 359 patients (23.4%) had a left ventricular ejection fraction of 40% or less in the alert and usual-care groups, respectively. The model achieved an area under the curve of 0.74 in the trial population. The primary outcome occurred in 619 patients (38.9%) in the alert group and 603 patients (39.3%) in the usual-care group (P = .89). There were no significant differences between study groups in the prescription of heart failure medications at discharge, the placement of an implantable cardioverter-defibrillator, or referral to palliative care., Conclusions and Relevance: Provision of 1-year mortality estimates during heart failure hospitalization did not affect hospitalization or mortality, nor did it affect clinical decision-making., Trial Registration: ClinicalTrials.gov Identifier NCT03845660.

Background: Recent evidence has shown that fine particulate matter (PM 2.5 ) may be an important environmental risk factor for chronic kidney disease (CKD), but few studies have examined this association for individual patients using fine spatial data., Objective: To investigate the association between PM 2.5 and CKD (estimated glomerular filtration rate [eGFR]<45 ml/min/1.73 m 2 ) in the Twin-Cities area in Minnesota using a large electronic health care database (2012-2019)., Methods: We estimated the previous 1-year average PM 2.5 from the first eGFR (measured with the CKD Epidemiology Collaboration equation using the first available creatinine measure during the baseline period [2012-2014]) using Environmental Protection Agency downscaler modeling data at the census tract level. We evaluated the spatial relative risk and clustering of CKD prevalence using a K-function test statistic. We assessed the prevalence ratio of the PM 2.5 association with CKD incidence using a mixed effect Cox model, respectively., Results: Patients (n = 20,289) in the fourth (PM 2.5  > 10.4), third (10.3 < PM 2.5  < 10.8) and second quartile (9.9 < PM 2.5  < 10.3) vs. the first quartile (<9.9 μg/m 3 ) had a 2.52[2.21, 2.87], 2.18[1.95, 2.45], and 1.72[1.52, 1.97] hazard rate of developing CKD in the fully adjusted models, respectively. We identified spatial heterogeneities and evidence of CKD clustering across our study region, but this spatial variation was accounted for by air pollution and individual covariates., Significance: Exposure to higher PM 2.5 is associated with a greater risk for incident CKD. Improvements in air quality, specifically at hotspots, may reduce CKD., (© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Importance: The cardiovascular and renal outcomes of angiotensin-II receptor blocker (ARB) and angiotensin-converting enzyme inhibitor (ACEI) treatment are well-known; however, few studies have evaluated initiation of these agents and cognitive impairment., Objective: To emulate a target trial to evaluate the cognitive outcomes of initiating an ARB- vs ACEI-based antihypertensive regimen in individuals at risk for mild cognitive impairment (MCI) and probable dementia (PD)., Design, Setting, and Participants: Active comparator, new-user observational cohort study design using data from the Systolic Blood Pressure Intervention Trial (SPRINT), conducted November 2010 through July 2018. Marginal cause-specific hazard ratios (HRs) and treatment-specific cumulative incidence functions were estimated with inverse probability (IP) weighting to account for confounding. Participants were using neither an ARB nor ACEI at baseline. Data analysis was conducted from April 7, 2021, to April 26, 2022., Exposures: New users of ARB vs ACEI during the first 12 months of trial follow-up., Main Outcomes and Measures: Composite of adjudicated amnestic MCI or PD., Results: Of 9361 participants, 727 and 1313 new users of an ARB or ACEI, respectively, with well-balanced baseline characteristics between medication exposure groups after inverse probability weighting (mean [SD] age, 67 [9.5] years; 1291 ]63%] male; 240 [33%] Black; 89 [12%] Hispanic; 383 [53%] White; and 15 [2%] other race or ethnicity. In the primary analysis, during a median follow-up of 4.9 years, the inverse probability-weighted rate of amnestic MCI or PD was 4.3 vs 4.6 per 100 person-years among participants initiating ARB vs ACEI (HR, 0.93; 95% CI, 0.76-1.13). In subgroup analyses, new users of an ARB vs ACEI had a lower rate of amnestic MCI or PD among those in the standard systolic blood pressure treatment arm (HR, 0.61; 95% CI, 0.41-0.91) but not in the intensive arm (HR, 1.17; 95% CI, 0.90-1.52) (P = .007 for interaction)., Conclusions and Relevance: In this observational cohort study of US adults at high cardiovascular disease risk, there was no difference in the rate of amnestic MCI or PD among new users of an ARB compared with ACEI, although 95% CIs were wide.

Background: The use of guideline-directed medical therapy (GDMT) is underprescribed in patients with heart failure with reduced ejection fraction (HFrEF)., Objectives: This study sought to examine whether targeted and tailored electronic health record (EHR) alerts recommending GDMT in eligible patients with HFrEF improves GDMT use., Methods: PROMPT-HF (PRagmatic trial Of Messaging to Providers about Treatment of Heart Failure) was a pragmatic, EHR-based, cluster-randomized comparative effectiveness trial. A total of 100 providers caring for patients with HFrEF were randomized to either an alert or usual care. The alert notified providers of individualized GDMT recommendations along with patient characteristics. The primary outcome was an increase in the number of GDMT classes prescribed at 30 days postrandomization. Providers were surveyed on knowledge of guidelines and user experience., Results: The study enrolled 1,310 ambulatory patients with HFrEF from April to October 2021. Median age was 72 years; 31% were female; 18% were Black; and median left ventricular ejection fraction was 32%. At baseline, 84% of participants were receiving β-blockers, 71% received a renin-angiotensin-aldosterone system inhibitor, 29% received a mineralocorticoid receptor antagonist, and 11% received a sodium-glucose cotransporter-2 inhibitor. The primary outcome occurred in 176 of 685 (26%) participants in the alert arm vs 117 of 625 (19%) in the usual care arm, thus increasing GDMT class prescription by >40% after alert exposure (adjusted relative risk: 1.41; 95% CI: 1.03-1.93; P = 0.03). The number of patients needed to alert to result in an increase in addition of GDMT classes was 14. A total of 79% of alerted providers agreed that the alert was effective at enabling improved prescription of medical therapy for HF., Conclusions: A real-time, targeted, and tailored EHR-based alerting system for outpatients with HFrEF led to significantly higher rates of GDMT at 30 days when compared with usual care. This low-cost intervention can be rapidly integrated into clinical care and accelerate adoption of high-value therapies in heart failure. (PRagmatic trial Of Messaging to Providers about Treatment of Heart Failure [PROMPT-HF; NCT04514458])., Competing Interests: Funding Support and Author Disclosures The PROMPT-HF trial was supported by AstraZeneca. Drs Huang, Olufade, and McDermott are employees of AstraZeneca. Dr Riello has received consulting fees from Alexion, AstraZeneca, Boehringer Ingelheim, Janssen, Johnson & Johnson, PhaseBio, and Portola. Dr Dhar has provided executive teaching for Sanofi Consumer Healthcare. Dr Inzucchi has served on clinical trial committees and advisory boards for Boehringer Ingelheim, AstraZeneca, and Novo Nordisk; has served as a consultant to Merck, Pfizer, Lexicon, vTv Therapeutics, Esperion, and Abbott; and has delivered lectures supported by Boehringer Ingelheim and AstraZeneca. Dr Wilson has received funding from National Institutes of Health grants R01DK113191 and P30DK079310. Dr Desai has worked under contract with the Centers for Medicare & Medicaid Services to develop and maintain performance measures used for public reporting and pay for performance programs; and has received research grants from and consulted for Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Cytokinetics, Novartis, SCPharmaceuticals, and Vifor. Dr Ahmad has received consulting fees from Sanofi, Amgen, and Cytokinetics; and has received research funding from Boehringer Ingelheim, AstraZeneca, Cytokinetics, and Relypsa. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To estimate the prevalence of secondary hypertension among otherwise healthy children with hypertension diagnosed in the outpatient setting., Study Design: The MEDLINE, PubMed Central, Embase, Web of Science, and Cochrane Library databases were systematically searched for observational studies reporting the prevalence of secondary hypertension in children who underwent evaluation for hypertension and had no known comorbidities associated with hypertension at the time of diagnosis. Two authors independently extracted the study-specific prevalence of secondary hypertension in children evaluated for hypertension. Prevalence estimates for secondary hypertension were pooled in a random-effects meta-analysis., Results: Nineteen prospective studies and 7 retrospective studies including 2575 children with hypertension were analyzed, with a median of 65 participants (range, 9-486) in each study. Studies conducted in primary care or school settings reported a lower prevalence of secondary hypertension (3.7%; 95% CI, 1.2%-7.2%) compared with studies conducted in referral clinics (20.1%; 95% CI, 11.5%-30.3%). When stratified by study setting, there were no significant subgroup differences according to study design, country, participant age range, hypertension definition, blood pressure device, or study quality. Although the studies applied different approaches to diagnosing secondary hypertension, diagnostic evaluations were at least as involved as the limited testing recommended by current guidelines., Conclusions: The low prevalence of secondary hypertension among children with a new diagnosis of hypertension identified on screening reinforces clinical practice guidelines to avoid extensive testing in the primary care setting for secondary causes in most children with hypertension., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Blood pressure (BP) elevations are commonly treated in hospitalized patients; however, treatment is not guideline directed. Our objective was to assess BP response to commonly prescribed antihypertensives after the development of severe inpatient hypertension (HTN)., Methods: This is a cohort study of adults, excluding intensive care unit patients, within a single healthcare system admitted for reasons other than HTN who developed severe HTN (systolic BP>180 or diastolic BP >110 mmHg at least 1 hour after admission). We identified the most commonly administered antihypertensives given within 6 hours of severe HTN (given to >10% of treated patients). We studied the association of treatment with each antihypertensive vs. no treatment on BP change in the 6 hours following severe HTN development using mixed-effects model after adjusting for demographics and clinical characteristics., Results: Among 23,147 patients who developed severe HTN, 9,166 received antihypertensive treatment. The most common antihypertensives given were oral metoprolol (n = 1991), oral amlodipine (n = 1812), oral carvedilol (n = 1116), IV hydralazine (n = 1069) and oral hydralazine (n = 953). In the fully adjusted model, treatment with IV hydralazine led to 13 [-15.9, -10.1], 18 [-22.2, -14] and 11 [-14.1, -8.3] mmHg lower MAP, SBP, and DBP in the 6 hours following severe HTN development compared to no treatment. Treatment with oral hydralazine and oral carvedilol also resulted in significantly lower BPs in the 6 hours following severe HTN development (6 [-9.1, -2.1 and -7 [-9.1, -4.2] lower MAP, respectively) compared to no treatment. Receiving metoprolol and amlodipine did not result in a drop in BP compared to no treatment., Conclusion: Among commonly used antihypertensives, IV hydralazine resulted in the most significant drop in BP following severe HTN, while metoprolol and amlodipine did not lower BP. Further research to assess the effect of treatment on clinical outcomes and if needed which antihypertensives to administer are necessary., Competing Interests: NO authors have competing interests

Severe hypertension (HTN) that develops during hospitalization is more common than admission for HTN; however, it is poorly studied, and treatment guidelines are lacking. Our goal is to characterize hospitalized patients who develop severe HTN and assess blood pressure (BP) response to treatment. This is a multi-hospital retrospective cohort study of adults admitted for reasons other than HTN who developed severe HTN. The authors defined severe inpatient HTN as the first documented BP elevation (systolic BP > 180 or diastolic BP > 110) at least 1 hour after admission. Treatment was defined as receiving antihypertensives (intravenous [IV] or oral) within 6h of BP elevation. As a measure of possible overtreatment, the authors studied the association between treatment and time to mean arterial pressure (MAP) drop ≥ 30% using the Cox proportional hazards model. Among 224 265 hospitalized adults, 10% developed severe HTN of which 40% were treated. Compared to patients who did not develop severe HTN, those who did were older, more commonly women and black, and had more comorbidities. Incident MAP drop ≥ 30% among treated and untreated patients with severe HTN was 2.2 versus 5.7/1000 person-hours. After adjustment, treated versus. untreated patients had lower rates of MAP drop ≥ 30% (hazard rate [HR]: 0.9 [0.8, 0.99]). However, those receiving only IV treatment versus untreated had greater rates of MAP drop ≥ 30% (1.4 [1.2, 1.7]). Overall, the authors found that clinically significant MAP drop is observed among inpatients with severe HTN irrespective of treatment, with greater rates observed among patients treated only with IV antihypertensives. Further research is needed to phenotype inpatients with severe HTN., (© 2022 The Authors. The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

Heart failure with reduced ejection fraction (HFrEF) is one of the most common chronic illnesses in the United States and carries significant risk of morbidity and mortality. Use of guideline-directed medical therapy (GDMT) for patients with HFrEF has been shown to dramatically improve outcomes, but adoption of these treatments remains generally low. Possible explanations for poor GDMT uptake include lack of knowledge about recommended management strategies and provider reluctance due to uncertainties regarding application of said guidelines to real-world practice. One way to overcome these barriers is by harnessing the electronic health record (EHR) to create patient-centered "best practice alerts" (BPAs) that can guide clinicians to prescribe appropriate medical therapies. If found to be effective, these low-cost interventions can be rapidly applied across large integrated healthcare systems. The PRagmatic Trial Of Messaging to Providers about Treatment of Heart Failure (PROMPT-HF) trial is a pragmatic, cluster randomized controlled trial designed to test the hypothesis that tailored and timely alerting of recommended GDMT in heart failure (HF) will result in greater adherence to guidelines when compared with usual care. PROMPT-HF has completed enrollment of 1,310 ambulatory patients with HFrEF cared for by 100 providers who were randomized to receive a BPA vs usual care. The BPA alerted providers to GDMT recommended for their patients and displayed current left ventricular ejection fraction (LVEF) along with the most recent blood pressure, heart rate, serum potassium and creatinine levels, and estimated glomerular filtration rate. It also linked to an order set customized to the patient that suggests medications within each GDMT class not already prescribed. Our goal is to examine whether tailored EHR-based alerting for outpatients with HFrEF will lead to higher rates of GDMT at 30 days post randomization when compared with usual care. Additionally, we are assessing clinical outcomes such as hospital readmissions and death between the alert versus usual care group. Trial Registration: Clinicaltrials.gov NCT04514458., (Copyright © 2021. Published by Elsevier Inc.)

Importance: Use of antihypertensive medications that stimulate type 2 and 4 angiotensin II receptors, compared with those that do not stimulate these receptors, has been associated with a lower risk of dementia. However, this association with cognitive outcomes in hypertension trials, with blood pressure levels in the range of current guidelines, has not been evaluated., Objective: To examine the association between use of exclusively antihypertensive medication regimens that stimulate vs inhibit type 2 and 4 angiotensin II receptors on mild cognitive impairment (MCI) or dementia., Design, Setting, and Participants: This cohort study is a secondary analysis (April 2011 to July 2018) of participants in the randomized Systolic Blood Pressure Intervention Trial (SPRINT), which recruited individuals 50 years or older with hypertension and increased cardiovascular risk but without a history of diabetes, stroke, or dementia. Data analysis was conducted from March 16 to July 6, 2021., Exposures: Prevalent use of angiotensin II receptor type 2 and 4-stimulating or -inhibiting antihypertensive medication regimens at the 6-month study visit., Main Outcomes and Measures: The primary outcome was a composite of adjudicated amnestic MCI or probable dementia., Results: Of the 8685 SPRINT participants who were prevalent users of antihypertensive medication regimens at the 6-month study visit (mean [SD] age, 67.7 [11.2] years; 5586 [64.3%] male; and 935 [10.8%] Hispanic, 2605 [30.0%] non-Hispanic Black, 4983 [57.4%] non-Hispanic White, and 162 [1.9%] who responded as other race or ethnicity), 2644 (30.4%) were users of exclusively stimulating, 1536 (17.7%) inhibiting, and 4505 (51.9%) mixed antihypertensive medication regimens. During a median of 4.8 years of follow-up (95% CI, 4.7-4.8 years), there were 45 vs 59 cases per 1000 person-years of amnestic MCI or probable dementia among prevalent users of regimens that contained exclusively stimulating vs inhibiting antihypertensive medications (hazard ratio [HR], 0.76; 95% CI, 0.66-0.87). When comparing stimulating-only vs inhibiting-only users, amnestic MCI occurred at rates of 40 vs 54 cases per 1000 person-years (HR, 0.74; 95% CI, 0.64-0.87) and probable dementia at rates of 8 vs 10 cases per 1000 person-years (HR, 0.80; 95% CI, 0.57-1.14). Negative control outcome analyses suggested the presence of residual confounding., Conclusions and Relevance: In this secondary analysis of SPRINT, prevalent users of regimens that contain exclusively antihypertensive medications that stimulate vs inhibit type 2 and 4 angiotensin II receptors had lower rates of incident cognitive impairment. Residual confounding cannot be ruled out. If these results are replicated in randomized clinical trials, certain antihypertensive medications could be prioritized to prevent cognitive decline.

Objective: To assess the nutritional status of patients on maintenance haemodialysis to determine the frequency and severity of malnutrition., Method: The cross-sectional study was conducted in November 2020, at the The Kidney Centre Post-Graduate Training Institute, Karachi, and comprised secondary data related to patients on maintenance haemodialysis which was collected from January to August 2016. A one-time subjective global assessment score was calculated based on the history and physical examinations. Data was analysed using SPSS 17., Results: Of the 150 patients, 84(56%) were male and 66(44%) were female. The overall mean age of study participants was 52.21±12.5 years. Hypertension was the most frequent comorbid 130(86.7%), and normal body mass index was noted in 58(38.7%). Overall, 96(64%) patients had mild or moderate malnourishment, and 54(36%) were well-nourished. Females were 2.6 times more likely to be malnourished (p=0.009), and duration >5 years on haemodialysis increased the risk of malnourishment by 12.5 times (p<0.001), while overweight patients had significantly less chance of being malnourished (p=0.004)., Conclusions: Malnutrition was found to be quite common in haemodialysis patients, which necessitates its regular assessment and monitoring.