Protocol-driven Approach Research Articles

Protocol-driven approach to guideline-directed medical therapy optimization for heart failure: A real-world application to recovery

The objective of our study was to evaluate the real-world effects of an aggressive, personalized protocol for guideline-directed medical therapy (GDMT) titration in patients with heart failure (HF) with reduced ejection fraction (HFrEF). We conducted a two-center retrospective cohort study. Patients with HFrEF who presented to a HF clinic from January 2020 to December 2022 were placed on a GDMT protocol. 180 patients were included in the study. Mean GDMT score significantly increased from 4.7 to 5.9 (p < 0.001) between initial and final visits. Mean left ventricular ejection fraction (LVEF) significantly increased from 28 % to 33 % (+5 %, p < 0.001). 27 (15.7 %) of the 172 patients with complete New York Heart Association (NYHA) classification data had improvement by at least 1 class, while 2 (1.2 %) patients had worsening NYHA classification. 140 (77.8 %) patients had no unplanned hospitalizations between visits. 21 (11.7 %) patients had an unplanned hospitalization for acute HF during the study period with a mean time from first clinic visit to hospitalization of 183 days (range: 13–821 days). 2 (1.1 %) patients were hospitalized due to GDMT-associated adverse drug events (i.e. hypotension, hyperkalemia). 7 (3.9 %) patients died during the study period, which was lower than the predicted 1-year death rate for our cohort (12.3 %) using the MAGGIC score. In conclusion, an aggressive, personalized protocol for GDMT titration in patients with HFrEF led to significant improvements in LVEF, NYHA classification, hospitalization, and mortality in a real-world setting. This protocol may help serve as a road map to lessen the gap between clinical knowledge and practice surrounding optimization of GDMT and move HFrEF patients toward a path to recovery.

Insight Into the Clinical Practices of US-Based Surgical Nongovernmental Organizations

IntroductionA growing sector of humanitarian surgical nongovernmental organizations (NGOs) is providing care in low- and middle-income countries. Minimal data exists regarding this extremely heterogeneous community. This study aims to describe the demographics and clinical practices of surgical NGOs. We hypothesize there are identifiable attributes of such organizations which correlate with success. MethodsA survey was sent to 83 US-based surgical NGOs directly providing general or subspecialty surgical care in low- and middle-income countries. Further information was obtained from organizations’ websites. Descriptive statistics were performed to analyze organizational attributes and define protocol-driven practices. ResultsThirty NGOs (36%) responded, averaging 20 ± 11 y of operation. Annually, US humanitarian surgical organizations performed a wide range of operations (10-15,000) with 52% performing fewer than 200 operations per year. Sixty-seven percent of responders were classified as strongly protocol-driven. Only twenty percent reported deviation from standard US practice occurs often or very often, most commonly in pain management (18%), preoperative workup (16%), and operative technique (16%). ConclusionsTo our knowledge, this is the first effort to describe the characteristics and clinical practices of the humanitarian surgical sector. There exists a wide scope of clinical practice among responding surgical NGOs, however mostly consistent with US standards, with a prevalance of protocol-driven clinical approach. Developing consensus-based protocols may help standardize and improve quality of care for surgical NGOs.

Is CRT Optimization Obsolete? A Referral Center's Experience.

Cardiac resynchronization therapy (CRT) is a well-established therapy for patients with heart failure (HF). However, 30% of HF patients do not show any improvement in clinical status after CRT implantation. In this study, we report our echocardiography-based CRT optimization methodology, in daily practice at our CRT referral center. We included 350 ambulatory patients, who were referred to our center for optimization after CRT implantation. A protocol-driven echocardiographic approach for adjusting mechanical dyssynchrony, whereby adjusting for ventriculoventricular (VV) delays with strain and atrioventricular (AV) delays with Doppler echocardiography was performed. We defined changes in left ventricular ejection fraction (LVEF) and New York Heart Association (NYHA) classes as outcome variables in the evaluation of the CRT outcomes. Optimization was obtained in 288 (82%) patients. VV and AV timings were adjusted to 61% and 51%, respectively. In 3%, biventricular pacing was turned off and in 3% left ventricular (LV) only pacing was programmed. The LVEF and NYHA class showed significant improvements in all patients who underwent CRT optimization. CRT optimization remains valuable in improving LVEF and functional status measured using the NYHA class in all patients receiving CRT devices.

Evaluating the Science to Inform the Physical Activity Guidelines for Americans Midcourse Report

Evaluating the Science to Inform the Physical Activity Guidelines for Americans Midcourse Report

Epidemiology, outcomes, and disproportionate burden of food-dependent exercise-induced anaphylaxis from the Hong Kong Multidisciplinary Anaphylaxis Management Initiative (HK-MAMI).

Anaphylaxis is a life-threatening allergic reaction that poses a considerable burden on populations across all ethnicities and age groups. The Hong Kong Multidisciplinary Anaphylaxis Management Initiative (HK-MAMI) was established to streamline the assessment of patients with anaphylaxis via a multidisciplinary and protocol-driven approach. This prospective study aims to define the etiology, clinical manifestations, and treatment of patients with anaphylaxis in Hong Kong. Prospective clinical data from allergologic investigations from patients who completed evaluation by the HK-MAMI pathway between January 2017 and August 2022 were analyzed. Of the 161 patients referred via the HK-MAMI, 131 (81.4%) met the diagnostic criteria for anaphylaxis. The median delay in diagnosis was 2 years (range 0-30 years). The majority of anaphylaxis cases were attributed to food-dependent exercise-induced anaphylaxis (FDEIA), especially wheat-dependent exercise-induced anaphylaxis. In acute management settings, paired tryptase samples were taken in only around one-third of anaphylaxis cases, with 82.5% of the samples demonstrating significant elevation. There was a general underprescription of adrenaline autoinjectors, especially for food-related anaphylaxis. Patients with FDEIA had later ages of onset and diagnosis, and they presented with more cardiovascular manifestations. Skin prick tests and specific IgE level tests were able to diagnose 95% of FDEIA cases. Our study highlights the significant burden of FDEIA, and especially WDEIA, in Hong Kong, its association with severe presentations, and difficulties encountered in emergency or primary care settings. We advocate appropriate adrenaline use during acute-care management and discharge plans, as well as taking serum mast cell tryptase samples during acute episodes. Interdisciplinary collaboration remains crucial to upholding proper and optimized care for patients with anaphylaxis in Hong Kong.

The Aetion Coalition to Advance Real-World Evidence through Randomized Controlled Trial Emulation Initiative: Oncology.

Legislative and technological advancements over the past decade have given rise to the proliferation of healthcare data generated from routine clinical practice, often referred to as real-world data (RWD). These data have piqued the interest of healthcare stakeholders due to their potential utility in generating evidence to support clinical and regulatory decision making. In the oncology setting, studies leveraging RWD offer distinct advantages that are complementary to randomized controlled trials (RCTs). They also permit the conduct of investigations that may not be possible through prospective designs due to ethics or feasibility. Despite its promise, the use of RWD for the generation of clinical evidence remains controversial due to concerns of unmeasured confounding and other sources of bias that must be carefully addressed in the study design and analysis. To facilitate a better understanding of when RWD can provide reliable conclusions on drug effectiveness, we seek to conduct 10 RWD-based studies that emulate RCTs in oncology using a systematic, protocol-driven approach described herein. Results of this investigation will help inform clinical, scientific, and regulatory stakeholders on the applications of RWD in the context of product labeling expansion, drug safety, and comparative effectiveness in oncology.

Characteristics Associated With Failure to Rescue After Open Abdominal Aortic Aneurysm Repair

IntroductionFailure to Rescue (FTR), defined as mortality following a complication of care, is an important indicator of hospital care quality. Understanding risk factors associated with FTR in the elective Abdominal Aortic Aneurysm (AAA) population may help surgeons prevent operative mortality. MethodsElective open AAA repairs (2008-2018) were identified from Cerner's HealthFacts database using ICD-9 and ICD-10 diagnosis and procedure codes. Patient, hospital, and encounter characteristics were analyzed. Multivariate logistic regression models determined the relative contribution of patient and encounter characteristics leading to FTR. ResultsFor 1761 patients who underwent open repair for nonruptured AAA, overall mortality was 6.1%. Of patients with one or more complications (40%), mortality was 9.6%, increasing to 21.5% for patients with ≥4 major complications. Complications of care most associated with death were myocardial infarction (MI), gastrointestinal (GI) bleeding, and pulmonary failure. After multivariable adjustment, FTR was associated with advanced age (odds ratio [OR] 1.19 for 5 y, 95% confidence interval [CI] 1.06-1.34); female sex (OR 1.74, 95% CI 1.12-2.70); congestive heart failure (OR 1.65, 95% CI 1.00-2.73); peptic ulcer disease (OR 3.99, 95% CI 1.18-13.5); diabetes (OR 4.90, 95% CI 1.90-12.6), and the number of complications of care. ConclusionsComplications of care were common following open elective AAA repair. The complications with the highest mortality included MI, GI bleeding, and respiratory failure. FTR was associated with female sex, comorbidities, and increasing numbers of complications of care. Often, the lowest occurring complications had the highest FTR. Adopting gender-specific assessment tools, a protocol-driven approach for perioperative GI prophylaxis, and preoperative MI risk mitigation may lead to reduced FTR.

A dual-center cohort study on the association between early deep sedation and clinical outcomes in mechanically ventilated patients during the COVID-19 pandemic: The COVID-SED study

BackgroundMechanically ventilated patients have experienced greater periods of prolonged deep sedation during the coronavirus disease (COVID-19) pandemic. Multiple studies from the pre-COVID era demonstrate that early deep sedation is associated with worse outcome. Despite this, there is a lack of data on sedation depth and its impact on outcome for mechanically ventilated patients during the COVID-19 pandemic. We sought to characterize the emergency department (ED) and intensive care unit (ICU) sedation practices during the COVID-19 pandemic, and to determine if early deep sedation was associated with worse clinical outcomes.Study design and methodsDual-center, retrospective cohort study conducted over 6 months (March–August, 2020), involving consecutive, mechanically ventilated adults. All sedation-related data during the first 48 h were collected. Deep sedation was defined as Richmond Agitation-Sedation Scale of − 3 to − 5 or Riker Sedation-Agitation Scale of 1–3. To examine impact of early sedation depth on hospital mortality (primary outcome), we used a multivariable logistic regression model. Secondary outcomes included ventilator-, ICU-, and hospital-free days.Results391 patients were studied, and 283 (72.4%) experienced early deep sedation. Deeply sedated patients received higher cumulative doses of fentanyl, propofol, midazolam, and ketamine when compared to light sedation. Deep sedation patients experienced fewer ventilator-, ICU-, and hospital-free days, and greater mortality (30.4% versus 11.1%) when compared to light sedation (p < 0.01 for all). After adjusting for confounders, early deep sedation remained significantly associated with higher mortality (adjusted OR 3.44; 95% CI 1.65–7.17; p < 0.01). These results were stable in the subgroup of patients with COVID-19.ConclusionsThe management of sedation for mechanically ventilated patients in the ICU has changed during the COVID pandemic. Early deep sedation is common and independently associated with worse clinical outcomes. A protocol-driven approach to sedation, targeting light sedation as early as possible, should continue to remain the default approach.

Nuances of Arteriovenous Fistula Creation for Vascular Access in Hemodialysis.

Background With rising incidence and increased life expectancy of patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD), the number of patients requiring hemodialysis has increased substantially. Vascular access is the lifeline for a patient on hemodialysis (HD), and an arteriovenous fistula (AVF) is the undisputed gold standard for HD access. An effective and long-lasting fistula serves to increase the life expectancy of ESRD patients and improves their quality of life. Learning Objectives This paper aims to give a comprehensive overview of AVF creation, including the various techniques, patient selection, troubleshooting with decision-making, and common complications. Authors share their experience from previous publications and over 2000 AVF surgeries. They have not only described a new modification of the technique of proximal fistula but have also established a direct correlation between bruit and thrill on operation table and success of fistula surgery. Conclusion A standardized, protocol-driven multidisciplinary approach with careful patient and site selection, guided by outcome predictors, is vital in AVF surgery. Knowledge about the potential complications of AVFs contributes to their timely detection and allows measures to be taken that might prevent deleterious consequences that range from loss of vascular access to serious morbidity and mortality.

Implementation of the Ebola Virus Persistence in Ocular Tissues and Fluids (EVICT) study: Lessons learned for vision health systems strengthening in Sierra Leone.

BackgroundFollowing the West African Ebola virus disease (EVD) outbreak of 2013–2016 and more recent EVD outbreaks in the Democratic Republic of Congo, thousands of EVD survivors are at-risk for sequelae including uveitis, which can lead to unremitting inflammation and vision loss from cataract. Because of the known risk of Ebola virus persistence in ocular fluid and the need to provide vision-restorative, safe cataract surgery, the Ebola Virus Persistence in Ocular Tissues and Fluids (EVICT) Study was implemented in Sierra Leone. During implementation of this multi-national study, challenges included regulatory approvals, mobilization, community engagement, infection prevention and control, and collaboration between multiple disciplines. In this report, we address the multifacted approach to address these challenges and the impact of implementation science research to address an urgent clinical subspecialty need in an outbreak setting.Methodology/Principal findingsGiven the patient care need to develop a protocol to evaluate ocular fluid for Ebola virus RNA persistence prior to cataract surgery, as well as protocols to provide reassurance to ophthalmologists caring for EVD survivors with cataracts, the EVICT study was designed and implemented through the work of the Ministry of Health, Sierra Leone National Eye Programme, and international partnerships. The EVICT study showed that all 50 patients who underwent ocular fluid sampling at 19 and 34 months, respectively, tested negative for Ebola virus RNA. Thirty-four patients underwent successful cataract surgery with visual acuity improvement. Here we describe the methodology for study implementation, challenges encountered, and key issues that impacted EVD vision care in the immediate aftermath of the EVD outbreak. Key aspects of the EVICT study included defining the pertinent questions and clinical need, partnership alignment with key stakeholders, community engagement with EVD survivor associations, in-country and international regulatory approvals, study site design for infection prevention and control, and thorough plans for EVD survivor follow-up care and monitoring. Challenges encountered included patient mobilization owing to transportation routes and distance of patients in rural districts. Strong in-country partnerships and multiple international organizations overcame these challenges so that lessons learned could be applied for future EVD outbreaks in West and Central Africa including EVD outbreaks that are ongoing in Guinea and Democratic Republic of Congo.Conclusions/SignificanceThe EVICT Study showed that cataract surgery with a protocol-driven approach was safe and vision-restorative for EVD survivors, which provided guidance for EVD ophthalmic surgical care. Ophthalmologic care remains a key aspect of the public health response for EVD outbreaks but requires a meticulous, yet partnered approach with international and local in-country partners. Future efforts may build on this framework for clinical care and to improve our understanding of ophthalmic sequelae, develop treatment paradigms for EVD survivors, and strengthen vision health systems in resource-limited settings.

Reducing Intubation Time in Adult Cardiothoracic Surgery Patients With a Fast-track Extubation Protocol.

Prolonged intubation after cardiac surgery increases the risk of morbidity and mortality and lengthens hospital stays. Factors that influence the ability to extubate patients with speed and efficiency include the operation, the patient's baseline physiological condition, workflow processes, and provider practice patterns. Progression to extubation lacked consistency and coordination across the team. The purpose of the project was to engage interprofessional stakeholders to reduce intubation times after cardiac surgery by implementing fast-track extubation and redesigned care processes. This staged implementation study used the Define, Measure, Analyze, Improve, and Control approach to quality improvement. Barriers to extubation were identified and reduced through care redesign. A protocol-driven approach to extubation was also developed for the cardiothoracic intensive care unit. The team was engaged with clear goals and given progress updates. In the preimplementation cohort, early extubation was achieved in 48 of 101 patients (47.5%) who were designated for early extubation on admission to the cardiothoracic intensive care unit. Following implementation of a fast-track extubation protocol and improved care processes, 153 of 211 patients (72.5%) were extubated within 6 hours after cardiac surgery. Reintubation rate, length of stay, and 30-day mortality did not differ between cohorts. The number of early extubations following cardiac surgery was successfully increased. Faster progression to extubation did not increase risk of reintubation or other adverse events. Using a framework that integrated personal, social, and environmental influences helped increase the impact of this project.

Management of In-laboratory Cardiopulmonary Arrest

The purpose of this review is to update the reader on the risk factors, causes, and mechanisms for cardiac arrest in the cardiac catheterization laboratory. In addition, the review provides a summary of recently published data specifically pertaining to the management of in-lab cardiac arrest. The incidence of cardiac arrest in unselected patients undergoing cardiac catheterization is approximately 0.5%. ST elevation myocardial infarction and cardiogenic shock account for the majority of cases. Pulseless electrical activity is the most common initial rhythm. Mechanical chest compression devices (especially if combined with a mechanical circulatory support device) can result in a high rate of return of spontaneous circulation, but survival is not different from patients receiving manual chest compressions. Case series have reported 40–60% short- and intermediate-term survival in patients treated with extracorporeal membrane oxygenation (ECMO) and correction of the underlying cause of cardiac arrest. A systematic and protocol-driven approach to the management of in-lab cardiac arrest is essential to patient survival. The rapid initiation of ECMO and comprehensive post-arrest care can result in relatively high rates of survival in selected patients.

82 Person-Centred Emergency Care Outcome Measurement For Older People Living with Frailty

IntroductionHealth outcome goals are the results individuals seek from healthcare. These may incorporate holistic themes including function, mood, and quality of life. People living with frailty have poorer outcomes from even short hospital stays. They benefit from person-centred, goal-directed care over protocol-driven pathway approaches. This could be improved by monitoring attainment of health outcome goals.MethodsA systematic review for older people’s health outcome goals in emergency care was conducted using narrative synthesis. A qualitative study based on grounded theory expanded the outcome framework to include people living with frailty. People with cognitive and communication barriers were included in semi-structured interviews. Discussions focussed on the events and outcomes sought from emergency care.ResultsOlder people’s health outcome goals for emergency care were classified as efficient and comprehensive care, sensitivity towards vulnerability, and person-centred informed care. The importance of understanding individual perceptions was explicit. Research generally recruited based on age rather than physiological and functional state, and did not assess for impact of frailty on healthcare perceptions. The interview study was paused due to the COVID-19 pandemic. Initial results showed a predominance of person-centred and holistic care themes among health outcome goals. Participants’ most common goal for emergency care was relief of symptoms: people often had pain. Participants mostly had severe frailty and wanted their mobility to be assessed, with goals of recovering their functional baseline. While participants had confidence in healthcare professionals and were generally willing to “do as we are told to feel better”, they expected to undergo at least basic tests in order to receive a working diagnosis for their problem. People wanted to understand their illness and for explanations to be communicated to their relatives. Next steps Patient-reported outcome measures (PROMs) for this range of emergency care outcomes are being identified for field-testing in acute settings.

Clinical impact of a pharmacist + health coach chronic disease management program in a rural free clinic

ObjectivesRecent data have demonstrated benefits of pharmacist-led protocols for chronic disease state management in the primary care setting. Health coaching has also been shown to improve patient outcomes and reduce health care costs. A program was initiated in August 2017 at a rural, free clinic to provide team-based, patient-centered care management through the use of pharmacist-provider collaborative practice and health coaching for patients with chronic diseases such as diabetes, hypertension, and hyperlipidemia. MethodsAfter an initial patient examination, physicians could refer patients for management by the pharmacist + health coach team. Patients continued to see their primary care provider at least yearly and as needed. The pharmacist + health coach team provided a protocol-based approach to chronic disease management, as well as health education pertaining to diet and lifestyle recommendations. In-depth medication and disease state education were provided at each visit. Motivational interviewing was also conducted at each visit. Clinical metrics were collected at baseline and analyzed routinely after program initiation, including glycosylated hemoglobin (A1c), blood pressure, and lipids. Primary objectives were to evaluate the program’s impact on A1c, blood pressure, and cholesterol outcomes. ResultsA total of 95 patients were included in the analysis (A1c n = 37; systolic and diastolic blood pressure n = 47; total cholesterol n = 40; low-density lipoprotein [LDL] cholesterol n = 38; high-density lipoprotein cholesterol n = 40; and triglycerides n = 40). From baseline to 1 year, statistically significant improvements were observed for A1c (mean ± standard deviation, 8.55 ± 2.58 to 7.04 ± 1.12, P < 0.001), systolic blood pressure (136.79 ± 20.04 to 123.15 ± 16.81, P < 0.001), diastolic blood pressure (87.94 ± 12.28 to 78.64 ± 10.98, P < 0.001), total cholesterol (198.25 ± 52.47 to 183.55 ± 47.22, P = 0.014), and LDL cholesterol (115.74 ± 43.56 to 105.92 ± 39.27, P = 0.040). ConclusionA protocol-driven collaborative practice approach to chronic disease management by a clinical pharmacist in conjunction with health coaching by a registered nurse in a low-income, rural, primary care setting improved A1c, blood pressure, total cholesterol, and LDL cholesterol.

Elderly hip fracture patients: surgical timing and factors to consider.

Hip fractures of the elderly population are a common trauma and numbers are increasing due to ageing societies. Although this is an ordinary low energy impact injury and surgical repair techniques show good results, the perioperative course is characterized by an unparalleled disproportionate perioperative morbidity and mortality. Most studies focus on outcome-related data. Little is known on how to prevent and treat adverse sequelae, ranging from mild physical challenges to neurobiological disorders and death. Although the contribution of the anaesthetic technique per se seems to be small, the role of the anaesthesiologist as a perioperative physician is undisputed. From focusing on comorbidities and initiating preoperative optimization to intraoperative and postoperative care, there is a huge area to be covered by our faculty to ensure a reasonable outcome defined as quality of postoperative life rather than merely in terms of a successful surgical repair. Protocol-driven perioperative approaches should be employed focusing on pre, intraoperative and postoperative optimization of the patient to facilitate early repair of the fracture that may then translate into better outcomes and hence alleviate the individual patient's burden as well as the socioeconomic load for society.

COVID-19: mobilising CT as a frontline management tool.

As the COVID-19 pandemic has spread across the globe, questions have arisen about the approach healthcare systems should adopt in order to optimally manage patient influx. With a focus on the impact of COVID-19 on the NHS, we describe the frontline experience of a severely affected hospital in close proximity to London. We highlight a protocol-driven approach, incorporating the use of CT in the rapid triage, assessment and cohorting of patients, in an environment where there was a lack of readily available, onsite RT-PCR testing facilities. Furthermore, the effects of the protocol on the effective streamlining of patient flow within the hospital are discussed, as are the resultant improvements in clinical management decisions within the acute care service. This model may help other healthcare systems in managing this pandemic whilst assessing their own needs and resources.

Protocol-driven Antibiotic Treatment of Pediatric Empyema After Fibrinolysis.

The duration of antibiotic treatment after resolution of empyema in children is variable. We evaluated the efficacy and safety of a protocol-driven antibiotic regimen aimed to decrease antibiotic duration following treatment with fibrinolysis. Our institutional protocol consisted of 7 further days of antibiotics upon removal of the thoracostomy tube, with the patient being afebrile, off supplemental oxygen, and having negative cultures. A prospective observational study was then performed between September 2014 and March 2019. Empyema recurrence and antibiotic-related complications were recorded. Results were compared with previously published data from the preprotocol era. A total of 37 patients were included. Mean total duration of antibiotics decreased from 26 ± 6.5 days in the preprotocol group to 22 ± 9.7 days in the postprotocol group (P = 0.004). This resulted in a significant decrease in hospital stay from the preprotocol cohort to the postprotocol cohort, respectively (9.3 ± 4.8 d versus 6.8 ± 3.1 d, P = 0.003). Sixty-two percentage of the patients were intended to treat according to the protocol, with a 50% adherence rate. Patients in which the protocol was followed had an average of 2.8 fewer days of antibiotics after discharge (P = 0.004), although overall duration was not statistically different. Significantly fewer antibiotic-related complications were noted after protocol initiation. There was no difference in empyema recurrence or readmissions. Institution of a protocol-driven approach to antibiotic duration following resolution of pleural space disease may reduce antibiotic duration and complications without reducing efficacy.

Pediatric asthma pathway in the emergency room

Asthma is one of the leading causes of hospital admission in the pediatric population. Standardization of asthma management guidelines for patients admitted to the emergency department has been suggested to improve care delivery and patient outcomes. Utilizing a multidisciplinary asthma task force at a single academic medical center, we sought to determine if a protocol-driven approach to implementation of care for patients with asthma could improve patient outcomes by reducing wait times for administration of steroids. A prospective cohort study examined the use of a standardized asthma pathway over a 2-year period compared to historical controls. Pathway use significantly decreased time to corticosteroid administration (45 vs. 29 min [year 1] and 20 min [year 2]; P < 0.0001). By implementing this standard of care at pediatric emergency departments, time to treatment can be decreased, therefore improving the morbidity and mortality of pediatric patients with asthma nationwide.

Assessment of Limitations to Optimization of Guideline-Directed Medical Therapy in Heart Failure From the GUIDE-IT Trial

Despite evidence that guideline-directed medical therapy (GDMT) improves outcomes in patients with heart failure (HF) and reduced ejection fraction, many patients are undertreated. The Guiding Evidence-Based Therapy Using Biomarker Intensified Treatment (GUIDE-IT) trial tested whether a strategy of using target concentrations of N-terminal pro-brain natriuretic peptide (NT-proBNP) to guide optimization of GDMT could improve outcomes. To examine medical therapy for HF in GUIDE-IT and potential reasons why the intervention did not produce improvements in medical therapy. GUIDE-IT, a randomized clinical trial performed at 45 sites in the United States and Canada, was conducted from January 16, 2013, to September 20, 2016. A total of 894 patients with HF and reduced ejection fraction (≤40%) were randomized to NT-proBNP-guided treatment with a goal to suppress NT-proBNP concentrations to less than 1000 pg/mL vs usual care. This secondary analysis examined the medical therapy titration and reasons why the intervention did not produce improvements in care and outcomes. Data were analyzed March 27 to June 28, 2019. For each encounter, medication titrations were captured. A reason was requested if a modification was not made. A Cox proportional hazards regression model was used to assess the independent association of drug class with outcomes. Among the 838 patients available for analysis (566 men [67.5%]; median age, 62.0 years), 6223 visits occurred during 24 months. Adjustments of HF medication were made during 2847 of 5218 qualified visits (54.6%) (all usual care visits and all guided care visits with NT-proBNP level ≥1000 pg/mL) in 862 patients (96.4%). Most adjustments occurred within the first 6 months, primarily within the first 6 weeks. The most common reasons for not adjusting were "clinically stable" and "already at maximally tolerated therapy." Only 130 patients (15.5%) achieved optimal GDMT (≥50% of the target dose of β-blockers or angiotensin-converting enzyme inhibitors/angiotensin receptor blockers or any dose of mineralocorticoid antagonists) at 6 months, an increase from the baseline (79 of 891 [8.9%]) but not different by treatment arm. Higher doses of β-blockers were associated with reduced risk of the composite outcome of HF hospitalization and cardiovascular death (hazard ratio [HR], 0.98; 95% CI, 0.97-1.00; P = .008) and of all-cause death (HR, 0.97; 95% CI, 0.95-0.99; P = .01). Higher doses of angiotensin-converting enzyme inhibitors (HR, 0.84; 95% CI, 0.75-0.93; P < .001) and angiotensin receptor blockers (HR, 0.84; 95% CI, 0.71-0.99; P = .04) were associated with reduced risk of all-cause death. Increasing doses of mineralocorticoid antagonists did not appear to be associated with improved outcomes. Despite a protocol-driven approach, many patients in GUIDE-IT did not receive medication adjustments and did not achieve optimal GDMT, including those with known elevated NT-proBNP concentrations. These results suggest that opportunities exist to titrate medications for maximal benefit in HF. GUIDE-IT may have failed to achieve treatment benefit because of therapeutic inertia in clinical practice, or current GDMT goals may be unrealistic. ClinicalTrials.gov Identifier: NCT01685840.

Lifestyle and Risk Factor Modification for Reduction of Atrial Fibrillation: A Scientific Statement From the American Heart Association.

Atrial fibrillation (AF), the most common sustained cardiac arrhythmia, is associated with substantial morbidity, mortality, and healthcare use. Great strides have been made in stroke prevention and rhythm control strategies, yet reducing the incidence of AF has been slowed by the increasing incidence and prevalence of AF risk factors, including obesity, physical inactivity, sleep apnea, diabetes mellitus, hypertension, and other modifiable lifestyle-related factors. Fortunately, many of these AF drivers are potentially reversible, and emerging evidence supports that addressing these modifiable risks may be effective for primary and secondary AF prevention. A structured, protocol-driven multidisciplinary approach to integrate lifestyle and risk factor management as an integral part of AF management may help in the prevention and treatment of AF. However, this aspect of AF management is currently underrecognized, underused, and understudied. The purpose of this American Heart Association scientific statement is to review the association of modifiable risk factors with AF and the effects of risk factor intervention. Implementation strategies, care pathways, and educational links for achieving impactful weight reduction, increased physical activity, and risk factor modification are included. Implications for clinical practice, gaps in knowledge, and future directions for the research community are highlighted.