Electronic health record alerts for management of heart failure with reduced ejection fraction in hospitalized patients: the PROMPT-AHF trial.

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 ß-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.

Alerting Clinicians to 1-Year Mortality Risk in Patients Hospitalized With Heart Failure: The REVEAL-HF Randomized Clinical Trial.

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.

Electronic Alerts to Improve Heart Failure Therapy in Outpatient Practice: A Cluster Randomized Trial.

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 ß-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]).

Proximity of snacks to beverages increases food consumption in the workplace: A field study.

In an effort to bolster employee satisfaction, many employers provide free snacks at the office. Unfortunately, keeping employees happy can conflict with the goal of keeping them healthy, since increased snacking at work can contribute to overeating and obesity. Building on the growing body of research in choice architecture, we tested one factor that might influence snack consumption without impacting satisfaction: the relative distance between snacks and beverages. In a large field study at Google, we measured snack consumption when snacks were closer to or farther from beverages. We found that employees who used the beverage station closer to the snack station were more likely to take a snack- the likelihood of snacking increased from 12% to 23% for men and from 13% to 17% for women when the beverage station closest to the snack station was used. These results imply that employers and even families could reduce snack consumption easily, cheaply, and without backlash, by increasing the relative distance between beverages and snacks.

Pooled Amplicon Deep Sequencing of Candidate Plasmodium falciparum Transmission-Blocking Vaccine Antigens.

Polymorphisms within Plasmodium falciparum vaccine candidate antigens have the potential to compromise vaccine efficacy. Understanding the allele frequencies of polymorphisms in critical binding regions of antigens can help in the designing of strain-transcendent vaccines. Here, we adopt a pooled deep-sequencing approach, originally designed to study P. falciparum drug resistance mutations, to study the diversity of two leading transmission-blocking vaccine candidates, Pfs25 and Pfs48/45. We sequenced 329 P. falciparum field isolates from six different geographic regions. Pfs25 showed little diversity, with only one known polymorphism identified in the region associated with binding of transmission-blocking antibodies among our isolates. However, we identified four new mutations among eight non-synonymous mutations within the presumed antibody-binding region of Pfs48/45. Pooled deep sequencing provides a scalable and cost-effective approach for the targeted study of allele frequencies of P. falciparum candidate vaccine antigens.

Positive consequences of conflict on decision making: when a conflict mindset facilitates choice.

Much research has shown that conflict is aversive and leads to increased choice deferral. In contrast, we have proposed that conflict can be beneficial. Specifically, exposure to nonconscious goal conflict can activate a mindset (a set of cognitive procedures) that facilitates the systematic processing of information without triggering the associated costs, such as negative affect and stress. In a conflict mindset, people should be better able to make tradeoffs and resolve choice conflict. We tested this proposition in 4 experiments, and demonstrated that priming conflicting goals before a decision increases choice in domains unrelated to the primed conflict. We further demonstrated that increased choice occurs because people in a conflict mindset process choice information more systematically, and we rule out several alternative explanations for the results.

Negativity bias and task motivation: testing the effectiveness of positively versus negatively framed incentives.

People are frequently challenged by goals that demand effort and persistence. As a consequence, philosophers, psychologists, economists, and others have studied the factors that enhance task motivation. Using a sample of undergraduate students and a sample of working adults, we demonstrate that the manner in which an incentive is framed has implications for individuals' task motivation. In both samples we find that individuals are less motivated when an incentive is framed as a means to accrue a gain (positive framing) as compared with when the same incentive is framed as a means to avoid a loss (negative framing). Further, we provide evidence for the role of the negativity bias in this effect, and highlight specific populations for whom positive framing may be least motivating. Interestingly, we find that people's intuitions about when they will be more motivated show the opposite pattern, with people predicting that positively framed incentives will be more motivating than negatively framed incentives. We identify a lay belief in the positive correlation between enjoyment and task motivation as one possible factor contributing to the disparity between predicted and actual motivation as a result of the framing of the incentive. We conclude with a discussion of the managerial implications for these findings.

Adding small differences can increase similarity and choice.

Similarity plays a critical role in many judgments and choices. Traditional models of similarity posit that increasing the number of differences between objects cannot increase judged similarity between them. In contrast to these previous models, the present research shows that introducing a small difference in an attribute that previously was identical across objects can increase perceived similarity between those objects. We propose an explanation based on the idea that small differences draw more attention than identical attributes do and that people's perceptions of similarity involve averaging attributes that are salient. We provide evidence that introducing small differences between objects increases perceived similarity. We also show that an increase in similarity decreases the difficulty of choice and the likelihood that a choice will be deferred.

Primary human parvovirus B19 infection in an HIV infected patient on antiretroviral therapy.

INTRODUCTION: Persons with HIV infection frequently present with anaemia from different causes, including use of antiretroviral therapy (typically zidovudine), iron deficiency, vitamin B12 deficiency, opportunistic infections (such as mycobacterial and fungal infections), chronic disease, AIDS-associated malignancies, autoimmune haemolysis, and direct effects of HIV infection itself. Persistent infection with Parvovirus B19 (B19) is an important treatable cause of anaemia in HIV-infected patients. CASE PRESENTATION: We present a case of anaemia in HIV positive patient who did not respond to change of drug therapy and nutritional supplements. Bone marrow biopsy suggested parvo virus infection. CONCLUSIONS: Chronic anaemia due to Parvo virus B19 infection is a treatable cause. Human Parvo virus B19 infection is a diagnosis of exclusion in patients who are started on antiretroviral therapy develop anaemia and later not responding to empirical management. Chronic anaemia requiring recurrent transfusions in HIV positive patient Parvo virus infection should be suspected and evaluated.

Schizosaccharomyces pombe Dss1p is a DNA damage checkpoint protein that recruits Rad24p, Cdc25p, and Rae1p to DNA double-strand breaks.

Schizosaccharomyces pombe Dss1p and its homologs function in multiple cellular processes including recombinational repair of DNA and nuclear export of messenger RNA. We found that Tap-tagged Rad24p, a member of the 14-3-3 class of proteins, co-purified Dss1p along with mitotic activator Cdc25p, messenger RNA export/cell cycle factor Rae1p, 19 S proteasomal factors, and recombination protein Rhp51p (a Rad51p homolog). Using chromatin immunoprecipitation, we found that Dss1p recruited Rad24p and Rae1p to the double-strand break (DSB) sites. Furthermore, Cdc25p also recruited to the DSB site, and its recruitment was dependent on Dss1p, Rad24p, and the protein kinase Chk1p. Following DSB, all nuclear Cdc25p was found to be chromatin-associated. We found that Dss1p and Rae1p have a DNA damage checkpoint function, and upon treatment with UV light Deltadss1 cells entered mitosis prematurely with indistinguishable timing from Deltarad24 cells. Taken together, these results suggest that Dss1p plays a critical role in linking repair and checkpoint factors to damaged DNA sites by specifically recruiting Rad24p and Cdc25p to the DSBs. We suggest that the sequestration of Cdc25p to DNA damage sites could provide a mechanism for S. pombe cells to arrest at G(2)/M boundary in response to DNA damage.

Demographics of a large cohort of urban chronic hepatitis C patients.

PURPOSE: Recent studies suggest that African Americans (AA) with chronic hepatitis C (CHC) differ from non-Hispanic whites (NHW) with respect to the natural history and mortality resulting from the complications of chronic liver disease. The aim of this study was to examine the demographics of a large cohort of CHC patients and identify potential differences between AA and NHW. METHODS: This is a retrospective analysis, consisting of 2,739 hepatitis C antibody-positive patients seen at Wayne State University between 1995 and 2005. Patient demographics, risk factors, comorbidities, alanine aminotransferase (ALT), aspartate aminotransferase (AST), serum hepatitis C (HCV) RNA levels, genotype, and liver biopsy results were recorded. RESULTS: AA constituted 75.4%, NHW 22.5%, and Asians or Hispanics 2.1% of the patients. Males predominated (58%), and the mean age of AA and NHW was 50.0 and 45.3 years, respectively (P

Current status of immunology research in India.

Rudimentary studies on aspects of biochemistry in India date back to 1927. But, in the field of Immunology, such studies were started by scholars only during early 1970s at the All India Institute of Medical Sciences, New Delhi, India. Science and Technology was not an immediate priority until 1961 due to domestic and political conditions in the country. We were then 11 years old since independence and our focus was on economic and social developments. Gradually, improvements were made in the field and now we have 15 to 20 major groups (small in size) of immunologists in the country, who have made significant contribution in the field during the last 8 to 10 years. Hence, we anticipate improvements in manpower and infrastructure in the near future.

Percutaneous liver biopsy is safe in chronic hepatitis C patients with end-stage renal disease.

BACKGROUND & AIMS: Liver biopsy is useful for staging fibrosis in chronic hepatitis C (CHC) patients with end-stage renal disease (ESRD) to determine renal transplant eligibility and to make CHC treatment decisions. There is concern about an increased risk associated with percutaneous liver biopsy (PCNB) in ESRD patients. We compared the safety of PCNB in CHC patients with and without ESRD. METHODS: We reviewed PCNBs performed between 1996 and 2004 for technique, histology, and complications in 78 ESRD patients with CHC and in 241 control patients with CHC and no renal failure, randomly matched for age, sex, and race. Platelet counts, prothrombin, and partial thromboplastin times, but not bleeding times, were checked before biopsy. Deamino-8-D-arginine vasopressin was not given before the biopsy. RESULTS: The mean age of the patients was 50 years; 72% were male, 97% were African American, and 3% were Caucasian. The control group had a significantly higher proportion of patients with advanced fibrosis (P < .04). Only 1 patient with ESRD (1.3%) developed a moderate complication. Five controls (2.1%) developed complications, 3 of which were severe. CONCLUSIONS: Severe complications after PCNB are uncommon, and patients with ESRD and CHC are at no increased risk. Testing for bleeding time and the routine use of deamino-8-D-arginine vasopressin are not necessary before PCNB in patients with ESRD.

Ultrasound diagnosis of fatty liver in patients with chronic liver disease: a retrospective observational study.

OBJECTIVES: Hepatic ultrasound (US) is readily available and physicians usually trust the results of an US report suggesting fatty liver, but there are conflicting reports on its accuracy, especially in patients with chronic liver disease (CLD). Therefore, we retrospectively examined liver biopsies in patients with CLD and compared the histologic results to the hepatic US findings. METHODS: Liver biopsies were graded for fat (grades 0 to 3), inflammation (grades 0 to 4), and fibrosis (stages 0 to 4) in 131 patients with CLD (89% had chronic hepatitis C). Hepatic US interpretations were grouped into 3 categories-"normal," "fatty liver," and "nonspecific." A secondary analysis was performed using 3 sonographic categories based on the echogenicity: normal, "increased echogenicity," and "heterogenous." The US results were then compared with the liver biopsy results. RESULTS: A normal US report was associated with many false negatives, as 25% of these patients had fat (grades 1 to 3) on biopsy; furthermore, 46% had "significant fibrosis" (stages 2 to 4) or "significant inflammation" (grades 2 to 4). A "fatty liver" interpretation correctly identified fat on biopsy in 36.4% and "significant fat" (grades 2 to 3) in 11.4%, but 66% had significant fibrosis or significant inflammation. An US with increased echogenicity correctly identified fat in 43.5% and significant fat in 19.4%, but 69.4% had significant fibrosis or significant inflammation. The sensitivity of an US ranged from 11.4% to 88.2% and the specificity ranged from 40.4% to 86.2%, depending on the degree of steatosis on biopsy and the sonographic interpretation being considered. CONCLUSIONS: US is inaccurate for diagnosing hepatic steatosis in patients with CLD. Echogenic abnormalities are more likely to be the result of fibrosis or inflammation in this setting.

Where there is a way, is there a will? The effect of future choices on self-control.

Choices often involve self-control conflicts such that options that are immediately appealing are less desirable in the long run. In the current research, the authors examine how viewing such a choice as one of a series of similar future choices rather than as an isolated decision decreases the preference for items requiring self-control. The authors show that (a) in a choice between a vice and a virtue, the share choosing vice increases when the decision is presented as one of a series of similar future choices versus when the same choice is viewed in isolation, and (b) the overall share choosing a vice increases when decisions are seen in connection with similar future choices. The findings contrast with the general wisdom that broader choice frames lead to the exercise of greater self-control. The authors propose that the context of similar future choices allows people to optimistically believe that they will choose a virtue in the future choice and hence provides them with a guilt-reducing justification to not exercise self-control in the present.

The nuclear export signal of splicing factor Uap56p interacts with nuclear pore-associated protein Rae1p for mRNA export in Schizosaccharomyces pombe.

Mammalian UAP56 or its homolog Sub2p in Saccharomyces cerevisiae are members of the ATP-dependent RNA helicase family and are required for splicing and nuclear export of mRNA. Previously we showed that in Schizosaccharomyces pombe Uap56p is critical for mRNA export. It links the mRNA adapter Mlo3p, a homolog of Yra1p in S. cerevisiae or Aly in mammals, to nuclear pore-associated mRNA export factor Rae1p. In this study we show that, in contrast to S. cerevisiae, Uap56p in S. pombe is not required for pre-mRNA splicing. The putative RNA helicase function of Uap56p is not required for mRNA export. However, the RNA-binding motif of Uap56p is critical for nuclear export of mRNA. Within Uap56p we identified nuclear import and export signals that may allow it to shuttle between the nucleus and the cytoplasm. We found that Uap56p interacts with Rae1p directly via its nuclear export signal, and this interaction is critical for the nuclear export activity of Uap56p as well as for exporting mRNA. RNA binding and the ability to shuttle between the nucleus and cytoplasm are important features of mRNA export carriers such as HIV-Rev. Our results suggest that Uap56p could function similarly as an export carrier of mRNA in S. pombe.

Subgoals as substitutes or complements: the role of goal accessibility.

The self-regulation process often involves breaking an ongoing goal (e.g., keeping in shape) into many individual, constituent subgoals that monitor actual actions (e.g., eating healthy meals, going to the gym). The article examines how pursuing each of these subgoals may influence subsequent goal pursuit. The authors show that when people consider success on a single subgoal, additional actions toward achieving a superordinate goal are seen as substitutes and are less likely to be pursued. In contrast, when people consider their commitment to a superordinate goal on the basis of initial success on a subgoal, additional actions toward achieving that goal may seem to be complementary and more likely to be pursued. These predictions were tested in four studies that explored the conditions under which subgoals attainment have a counterproductive versus favorable effect on further pursuit of similar actions.