Cardiology Commons^™

The Utility Of Has-Bled Score In Predicting The Bleeding Risk Of Atrial Fibrillation Patients Undergoing Percutaneous Coronary Intervention Receiving Anticoagulation And Dual Anti-Platelet Therapy: A Single Center Retrospective Cohort Study, Luk Yin Cheung Adrian, Chan Chi Lin Jaclyn

Journal of the Hong Kong College of Cardiology

Background The Hypertension, Abnormal renal/liver function, Stroke, Bleeding history or predisposition, Labile international normalized ratio, Elderly and Drugs/alcohol (HAS-BLED) score is a validated bleeding risk prediction tool in patients with atrial fibrillation taking oral anticoagulation. Its predictive value in patients with atrial fibrillation undergoing percutaneous coronary intervention receiving combination of anticoagulation and antiplatelet therapy is unknown. This retrospective cohort study sought to validate the accuracy of HAS-BLED score in predicting the bleeding risk in patients with atrial fibrillation who underwent percutaneous coronary intervention receiving both anticoagulation and dual antiplatelet therapy. Method We calculated HAS-BLED score in 186 patients with AF …

Prognostic Nutritional Index As A Predictor Of Prognosis In Patients With Chronic Limb Threatening Ischemia Who Underwent Endovascular Revascularization Therapy, Wai Kin Chi, Gm Tan, Bryan Py Yan

Journal of the Hong Kong College of Cardiology

BACKGROUND/INTRODUCTION: Patients with chronic limb-threatening ischemia (CLTI) have poor prognosis. Prognostic nutritional index (PNI) is an established independent predictor of adverse outcome in various chronic illnesses. The use of PNI in patients with CLTI has not been studied.

PURPOSE: To evaluate the impact of PNI on 12-month adverse cardiovascular and limb outcomes in CLTI patients after endovascular revascularization therapy (ERT).

METHODS: 270 consecutive patients with CLTI (mean age 73.7±11.9 years; 53% male) who underwent ERT at a single tertiary referral hospital between January 2009 and October 2016 were prospectively enrolled and analyzed. Patients were grouped by tertiles of PNI (lowest …

Usefulness Of Computed Tomography Parameters In Predicting The Clinical Outcomes Of Acute Aortic Dissection, Eleanor Wei Sze Lee, Kwok Hin Yiu, Willis Chun Wai Lam, Cyrus Yiu Kwan Ko, Sung Yee Wong, Kin Wing Chan

Journal of the Hong Kong College of Cardiology

Background

Acute aortic dissection is a potentially life-threatening condition among patients presenting with chest pain to emergency department. Without a prompt diagnosis and treatment, it carries high mortality and morbidity. Computed tomography (CT) of thorax and abdomen is one of the commonly used non-invasive investigation modalities for diagnosis of acute aortic dissection. Apart from making a diagnosis, there are a number of parameters in the CT images that may be helpful in providing prognostic information. In this study, prognostic values of these parameters in predicting both short term and intermediate term clinical outcomes of acute aortic dissection will be evaluated. …

Effect Of Low Body Mass Index In Outcome Of Micra Leadless Pacemaker Implantation, Mark Tsz Kin Tam, Anna Kin Yin Chan, Alex Chi Kin Au, Lily Cheung, Gary Chin Pang Chan, Joseph Yat Sun Chan

Journal of the Hong Kong College of Cardiology

Background

Implantation of Micra transcatheter pacing system (TPS) requires introduction of a large caliber delivery catheter into patient’s venous system and right heart. While the investigational device exemption study population had a mean body mass index (BMI) of 27.6kg/m2, implantation outcome in patients with small body size requires further investigation. This study sort to evaluate the effect of low BMI in outcome of Micra TPS implantation Method

Consecutive patients undergoing Micra TPS implantation between 19 September 2015 and 24 May 2018 in a single tertiary referral center were studied. Procedure efficacy outcome was defined as successful implantation with threshold being …

The Risk Is Small: Implant Complications Of Leadless Pacemakers Are Related To Body Size, Chu-Pak Lau

Journal of the Hong Kong College of Cardiology

No abstract provided.

Cardiac Metastasis After Curative Treatment Of Hepatocellular Carcinoma: Risk Factors, Treatment Options, And Prognosis, Gaurav Jain, Mathew Otto, Mubeen Khan Mohammed Abdul, Manpreet Chadha, Ajay Sahajpal

Journal of Patient-Centered Research and Reviews

Hepatocellular carcinoma (HCC) is primary hepatic malignancy with a high incidence of recurrence. The risk of recurrence directly correlates to patient’s overall prognosis. Management of advanced HCC involves a combination of surgical resection, locoregional therapy, and systemic treatment. Distant metastases are rare, and intraventricular cardiac metastases are even more infrequent. This brief review details an illustrative case of cardiac metastasis after curative treatment of primary HCC and then summarizes the literature on risk factors, treatment options, and patient prognosis in the setting of distant metastases from HCC. Prognosis of metastasis to the heart is generally poor, and available evidence emphasizes …

Is Home Blood Pressure Monitoring Effective At Controlling Hypertension In African American Patients? A Clin-Iq, Rebecca Nye, Wilhelm Lehmann, Deborah Simpson

Journal of Patient-Centered Research and Reviews

African Americans are disproportionately affected by hypertension, a modifiable contributor to multiple chronic diseases and premature death. Primary care physicians play an important role in hypertension control. Home blood pressure monitoring (HBPM) is an evidence-based method for confirming diagnosis and monitoring hypertension over time. Some studies have found that HBPM may lead to clinically relevant reductions in blood pressure when combined with additional interventions, but few studies have focused specifically on African American populations. Evidence of effectiveness could increase clinical recommendation of HBPM. This clinical inquiry examined whether HBPM improves blood pressure control in African Americans with uncontrolled hypertension. Reviewed …

Editorial: Physiologic Signals In Neonatal Intensive Care, Eric W Reynolds

Faculty, Staff and Student Publications

No abstract provided.

Utility Of Av Nodal Characteristics In Identification Of Atrioventricular Nodal Reentrant Tachycardia And Risk Of Recurrence, Kimberly M. Decarr

Longitudinal Scholar's Project

Background: Catheter ablation of the slow atrioventricular (AV) nodal pathway is a safe and effective treatment for atrioventricular nodal reentrant tachycardia (AVNRT). While AVNRT occurs frequently in both children and adults, pediatric patients experience higher rates of AVNRT recurrence.

Objective: The purpose of this study was to characterize changes in AV nodal conduction properties following catheter ablation and correlate these properties with AVNRT recurrence in pediatric patients.

Methods: This was a retrospective review of patients aged(AVRT) at a single tertiary care center between January 01, 2010 and September 01, 2021. Demographics, pre- and post-ablation ECG intervals, and AV nodal conduction …

Global Think Tank On The Clinical Considerations And Management Of Lipoprotein(A): The Top Questions And Answers Regarding What Clinicians Need To Know, Salim S. Virani, Marlys L. Koschinsky, Lisa Maher, Anurag Mehta, Carl E. Orringer, Raul D. Santos, Michael D. Shapiro, Joseph J. Saseen

Office of the Provost

Evidence from Mendelian randomization studies suggest that lipoprotein(a) (Lp(a)) has a causal role in the development of atherosclerotic cardiovascular disease risk. However, guidelines and consensus statement recommendations vary regarding how clinicians should incorporate Lp(a) into patient care. To provide practical answers to key questions pertaining to Lp(a) that clinicians will find useful when assessing and treating patients, a global think tank was convened. Representatives from seven national and international stakeholder organizations answered questions that were focused on: Lp(a) measurement; ethnic, gender, and age considerations; factoring Lp(a) into risk assessment; and current and emerging treatment options for elevated Lp(a). This manuscript …

Heart Transplant Recipient 1-Year Outcomes During The Covid-19 Pandemic, Gabriel Esmailian, Nikhil Patel, Jignesh K Patel, Lawrence Czer, Matthew Rafiei, Dominick Megna, Dominic Emerson, Danny Ramzy, Alfredo Trento, Joanna Chikwe, Fardad Esmailian, Jon A Kobashigawa

Faculty, Staff and Student Publications

The COVID-19 pandemic initially brought forth considerable challenges to the field of heart transplantation. To prevent the spread of the virus and protect immunocompromised recipients, our center made the following modifications to post-transplant outpatient management: eliminating early coronary angiograms, video visits for postoperative months 7, 9, and 11, and home blood draws for immunosuppression adjustments. To assess if these changes have impacted patient outcomes, the current study examines 1-year outcomes for patients transplanted during the pandemic. Between March and September 2020, we assessed 50 heart transplant patients transplanted during the pandemic. These patients were compared to patients who were transplanted …

Myocardial Scintigraphy In Diagnosing Cardiac Transthyretin Amyloidosis, Marija Petrovic, Persio D Lopez, Calvin Eng, Mahjabeen Rashid

The Texas Heart Institute Journal

Myocardial scintigraphy with technetium-99m pyrophosphate is a minimally invasive technique that can distinguish between transthyretin amyloidosis (ATTR) and light-chain amyloidosis. We present a case in which it helped determine the amyloidosis type in a 74-year-old man with cardiac amyloidosis and multiple previous admissions for acute decompensated heart failure. The patient presented with increasing abdominal girth and bilateral lower extremity edema. His medical history also included atrial fibrillation, liver cirrhosis, hypertension, stage 3 chronic kidney disease, and peripheral vascular disease. We prescribed guideline-directed medical therapy for his acute decompensated heart failure with cardiorenal syndrome and his decompensated cirrhosis. Two years previously, …

Papillary Fibroelastoma Incidentally Found On Left Atrial Wall During Minimally Invasive Aortic Valve Replacement, Qasim Al Abri, Lamees I El Nihum, M Mujeeb Zubair, Roberto Barrios, Michael J Reardon, Mahesh Ramchandani

The Texas Heart Institute Journal

A 60-year-old man was about to undergo minimally invasive aortic valve replacement when transesophageal echocardiography revealed an intracardiac mass on the left atrial free wall. Multimodal images from 5 months earlier had shown no mass. We converted the procedure to open surgery. The excised mass resembled a cardiac myxoma but was determined to be a papillary fibroelastoma. This case illustrates that papillary fibroelastomas can form and grow rapidly, warranting alertness for their unexpected discovery before and during cardiac surgical procedures.

Comparison Of Different Metrics Of Cerebral Autoregulation In Association With Major Morbidity And Mortality After Cardiac Surgery, Xiuyun Liu, Joseph Donnelly, Ken M Brady, Kei Akiyoshi, Brian Bush, Raymond C Koehler, Jennifer K Lee, Charles W Hogue, Marek Czosnyka, Peter Smielewski, Charles H Brown

Faculty, Staff and Student Publications

BACKGROUND: Cardiac surgery studies have established the clinical relevance of personalised arterial blood pressure management based on cerebral autoregulation. However, variabilities exist in autoregulation evaluation. We compared the association of several cerebral autoregulation metrics, calculated using different methods, with outcomes after cardiac surgery.

METHODS: Autoregulation was measured during cardiac surgery in 240 patients. Mean flow index and cerebral oximetry index were calculated as Pearson's correlations between mean arterial pressure (MAP) and transcranial Doppler blood flow velocity or near-infrared spectroscopy signals. The lower limit of autoregulation and optimal mean arterial pressure were identified using mean flow index and cerebral oximetry index. …

Obscurin Regulates Ankyrin Macromolecular Complex Formation, Janani Subramaniam, Gokay Yamankurt, Shane R Cunha

Faculty, Staff and Student Publications

Obscurin is a large scaffolding protein in striated muscle that maintains sarcolemmal integrity and aligns the sarcoplasmic reticulum with the underlying contractile machinery. Ankyrins are a family of adaptor proteins with some isoforms that interact with obscurin. Previous studies have examined obscurin interacting with individual ankyrins. In this study, we demonstrate that two different ankyrins interact with obscurin's carboxyl terminus via independent ankyrin-binding domains (ABDs). Using in-vitro binding assays, co-precipitation assays, and FLIM-FRET analysis, we show that obscurin interacts with small ankyrin 1.5 (sAnk1.5) and the muscle-specific ankyrin-G isoform (AnkG107). While there is no direct interaction between sAnk1.5 and AnkG107, …

Prolonged Cardiac Nr4a2 Aactivation Causes Dilated Cardiomyopathy In Mice, Sadia Ashraf, Heinrich Taegtmeyer, Romain Harmancey

Faculty, Staff and Student Publications

Transcription factors play a fundamental role in cardiovascular adaptation to stress. Nuclear receptor subfamily 4 group A member 2 (NR4A2; NURR1) is an immediate-early gene and transcription factor with a versatile role throughout many organs. In the adult mammalian heart, and particularly in cardiac myocytes, NR4A2 is strongly up-regulated in response to beta-adrenergic stimulation. The physiologic implications of this increase remain unknown. In this study, we aimed to interrogate the consequences of cardiac NR4A2 up-regulation under normal conditions and in response to pressure overload. In mice, tamoxifen-dependent, cardiomyocyte-restricted overexpression of NR4A2 led to cardiomyocyte hypertrophy, left ventricular dilation, heart failure, …

Cardiovascular Disease Awareness Program On Risk Factors For Cardiovascular Disease Among Adolescents In Selected Schools, In New Delhi, Komal Kumari

Manipal Journal of Nursing and Health Sciences

Introduction: Cardiovascular disease (CVD) is the main cause of mortality worldwide. The main risk factors include tobacco chewing/smoking, higher blood cholesterol, high blood pressure, physical inactivity, obesity, excessive alcohol use, age, sex, and heredity. Although CVDs commonly develop in middle age or later, risk factors are highly impacted by childhood practices that are continued into maturity. Knowledge gaps on CVD and its risk factors are major obstacles to effective prevention and treatment. Hence, a CVD awareness program was organized in order to educate adolescents about CVD and its risk factors. Objective: The objectives of the study were to identify students’ …

Thrombotic Left Main Coronary Artery Occlusion Treated With Bioresorbable Scaffold, Santiago Jesús Camacho Freire, Antonio Enrique Gómez Menchero, Jessica Roa Garrido, Marcos López Rojas, Rosa Cardenal Piris, José Francisco Díaz Fernández

The Texas Heart Institute Journal

No abstract provided.

Decongestion Models And Metrics In Acute Heart Failure: Escape Data In The Age Of The Implantable Cardiac Pressure Monitor, David Paniagua, Glenn N Levine, Lorraine D Cornwell, Ernesto Jimenez, Biswajit Kar, Hani Jneid, Ali E Denktas, Tony S Ma

The Texas Heart Institute Journal

The United States Food and Drug Administration restricts the use of implantable cardiac pressure monitors to patients with New York Heart Association (NYHA) class III heart failure (HF). We investigated whether single-pressure monitoring could predict survival in HF patients as part of a model constructed using data from the ESCAPE (Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness) trial.

We validated survival models in 204 patients, using all-cause 180-day mortality. Two levels of model complexity were tested: 1) a simplified 1-pressure model based on pulmonary artery mean pressure ([PAM]1P) (information obtainable from an implanted intracardiac monitor alone), …

Mitral Regurgitation And Serum N-Terminal Pro-Brain Natriuretic Peptide Levels In Children: A Modification Of Adult Criteria, Elif Erolu, Figen Akalin

The Texas Heart Institute Journal

Mitral regurgitation can result from congenital heart disease, rheumatic valve disease, or other congenital malformations of the mitral valve. Faulty valves require surgical repair or replacement. However, echocardiographic and biochemical parameters that inform surgical decision-making for adults may not be appropriate for children. To investigate whether adult parameters can be used in children, we correlated echocardiographic parameters with serum N-terminal pro-brain natriuretic peptide (NT-proBNP) levels in children with chronic mitral regurgitation.

Our sample comprised 45 patients and 38 healthy children. M-mode measurements, left atrial and left ventricular volumes, and Doppler and tissue Doppler echocardiograms were collected. We graded mitral regurgitation …

Does Individualized Guided Selection Of Antiplatelet Therapy Improve Outcomes After Percutaneous Coronary Intervention? A Systematic Review And Meta-Analysis, Naser Yamani, Samuel Unzek, Muhammad Hasnain Mankani, Talal Almas, Adeena Musheer, Humera Qamar, Shausha Farooq, Waqas Shahnawaz, Kaneez Fatima, Vincent Figueredo

Department of Medicine

Background: The potential benefits of individualized guided selection of antiplatelet therapy over standard antiplatelet therapy in improving outcomes in patients undergoing percutaneous coronary intervention (PCI) have not been established. Therefore, we pooled evidence from available clinical trials to assess the effectiveness by comparing the two regimens in patients undergoing PCI.
Methods: We queried two electronic databases, MEDLINE and Cochrane CENTRAL, from their inception to April 20, 2021 for published randomized controlled trials in any language that compared guided antiplatelet therapy, using either genetic testing or platelet function testing, versus standard antiplatelet therapy in patients undergoing PCI. The results from trials …

Potential Impact Of 2017 American College Of Cardiology/American Heart Association Hypertension Guideline On Contemporary Practice: A Cross-Sectional Analysis From Ncdr Pinnacle Registry, Aliza Hussain, Salim S. Virani, Luke Zheng, Ty J. Gluckman, William B. Borden, Frederick A. Masoudi, Thomas M. Maddox

Office of the Provost

Background Clinical implications of change in the 2017 American College of Cardiology (ACC)/American Heart Association (AHA) guideline on the diagnosis and management of hypertension, compared with recommendations by 2014 expert panel and Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC7), are not known. Methods and Results Using data from the NCDR (National Cardiovascular Data Registry) PINNACLE (Practice Innovation and Clinical Excellence) Registry (January 2013-Decemver 2016), we compared the proportion and clinical characteristics of patients seen in cardiology practices diagnosed with hypertension, recommended antihypertensive treatment, and achieving blood pressure (BP) goals …

Rural-Urban Trends In Congenital Heart Disease-Related Mortality In The United States, 1999 To 2019, Abdul Mannan Khan Minhas, Rachel A. Wyand, Robert W. Ariss, Salik Nazir, Vardhmaan Jain, Sadeer G. Al-Kindi, Michael D. Shapiro, William Campbell, Laurence Sperling, Salim S. Virani

Office of the Provost

No abstract provided.

Prescriptions For Potentially Inappropriate Medications From The Beers Criteria Among Older Adults Hospitalized For Heart Failure, Diana Jaber, Fabian Vargas, Linh Nguyen, Joanna Ringel, Kate Zarzuela, Mahad Musse, Min Ji Kwak, Emily B Levitan, Mathew S Maurer, Mark S Lachs, Monika M Safford, Parag Goyal

Faculty, Staff and Student Publications

BACKGROUND: We sought to better understand patterns of potentially inappropriate medications (PIMs) from the Beers criteria among older adults hospitalized with heart failure (HF). This observational study of hospitalizations was derived from the geographically diverse REasons for Geographic and Racial Differences in Stroke cohort.

METHODS AND RESULTS: We examined participants aged 65 years and older with an expert-adjudicated hospitalization for HF. The Beers criteria medications were abstracted from medical records. The prevalence of PIMs was 61.1% at admission and 64.0% at discharge. Participants were taking a median of 1 PIM (interquartile range [IQR] 0-1 PIM) at hospital admission and a …

Impact Of Post-Arrest Care Variation On Hospital Performance After Out-Of-Hospital Cardiac Arrest, Ryan Huebinger, Jordan Thomas, Benjamin S Abella, John Waller-Delarosa, Rabab Al-Araji, Richard Witkov, Normandy Villa, Peter Nikonowicz, Taylor Renbarger, Micah Panczyk, Bentley Bobrow

Faculty, Staff and Student Publications

BACKGROUND: Large variation exists for out-of-hospital-cardiac-arrest (OHCA) prehospital care, but less is known about variations in post-arrest care. We sought to evaluate variation in post-arrest care in Texas as well as factors associated with higher performing hospitals.

METHODS: We analyzed data in Texas Cardiac Arrest Registry to Enhance Survival (TX-CARES), including all adult, non-traumatic OHCAs from 1/1/2014 through 12/31/ 2020 that survived to hospital admission. We first evaluated variability in provisions of post-arrest care and outcomes. We then stratified hospitals into quartiles based on their rate of survival and evaluated the association between improving quartiles and care. Lastly, we evaluated …

Influence Of The Human Lipidome On Epicardial Fat Volume In Mexican American Individuals, Ana C. Leandro, Laura F. Michael, Marcio Almeida, Mikko Kuokkanen, Kevin Huynh, Corey Giles, Thy Duong, Vincent P. Diego, Ravindranath Duggirala, Geoffrey D. Clarke, John Blangero, Joanne E. Curran

School of Medicine Publications

Introduction: Cardiovascular disease (CVD) is the leading cause of mortality worldwide and is the leading cause of death in the US. Lipid dysregulation is a well-known precursor to metabolic diseases, including CVD. There is a growing body of literature that suggests MRI-derived epicardial fat volume, or epicardial adipose tissue (EAT) volume, is linked to the development of coronary artery disease. Interestingly, epicardial fat is also actively involved in lipid and energy homeostasis, with epicardial adipose tissue having a greater capacity for release and uptake of free fatty acids. However, there is a scarcity of knowledge on the influence of plasma …

Cardiovascular Outcomes In Aortopathy: Gentac Registry Of Genetically Triggered Aortic Aneurysms And Related Conditions, Kathryn W Holmes, Sheila Markwardt, Kim A Eagle, Richard B Devereux, Jonathan W Weinsaft, Federico M Asch, Scott A Lemaire, Cheryl L Maslen, Howard K Song, Dianna M Milewicz, Siddharth K Prakash, Dongchuan Guo, Shaine A Morris, Reed E Pyeritz, Rita C Milewski, William J Ravekes, H C Dietz, Ralph V Shohet, Michael Silberbach, Mary J Roman

Faculty, Staff and Student Publications

BACKGROUND: The GenTAC (Genetically Triggered Thoracic Aortic Aneurysm and Cardiovascular Conditions) Registry enrolled patients with genetic aortopathies between 2007 and 2016.

OBJECTIVES: The purpose of this study was to compare age distribution and probability of elective surgery for proximal aortic aneurysm, any dissection surgery, and cardiovascular mortality among aortopathy etiologies.

METHODS: The GenTAC study had a retrospective/prospective design. Participants with bicuspid aortic valve (BAV) with aneurysm (n = 879), Marfan syndrome (MFS) (n = 861), nonsyndromic heritable thoracic aortic disease (nsHTAD) (n = 378), Turner syndrome (TS) (n = 298), vascular Ehlers-Danlos syndrome (vEDS) (n = 149), and Loeys-Dietz syndrome …

Sex Differences In The Association Between Cardiovascular Diseases And Dementia Subtypes: A Prospective Analysis Of 464,616 Uk Biobank Participants, Caiyun Dong, Chunmiao Zhou, Chunying Fu, Wenting Hao, Akihiko Ozaki, Nipun Shrestha, Salim S. Virani, Shiva Raj Mishra, Dongshan Zhu

Office of the Provost

Background: Whether the association of cardiovascular diseases (CVDs) with dementia differs by sex remains unclear, and the role of socioeconomic, lifestyle, genetic, and medical factors in their association is unknown.
Methods: We used data from the UK Biobank, a population-based cohort study of 502,649 individuals. We used Cox proportional hazards models to estimate sex-specific hazard ratios (HRs) and 95% confidence intervals (CI), and women-to-men ratio of HRs (RHR) for the association between CVD (coronary heart diseases (CHD), stroke, and heart failure) and incident dementia (all-cause dementia, Alzheimer's Disease (AD), and vascular dementia (VD)). The moderator roles of socioeconomic (education, income), …

A Fatal Case Of Covid-19 Pneumonia In A Fully Vaccinated Heart Transplant Recipient, Agastya D. Belur, Diana Otero, Christina Dunbar Matos

The University of Louisville Journal of Respiratory Infections

The development and administration of mRNA vaccines against SARS-CoV-2 are seeing lower numbers of COVID-19 cases and fatalities among fully vaccinated, immunocompetent adults. We present a case of fatal COVID-19 pneumonia in a heart transplant recipient who had received two doses of mRNA COVID-19 vaccine before the Centers for Disease Control and Prevention had recommended additional doses.

Case Report And Review: Spontaneous Coronary Artery Dissection (Scad), Michael Morris, Wayne Tamaska, James Espinosa, Alan Lucerna, Trent Malcolm

Rowan-Virtua Research Day

Spontaneous coronary artery dissection (SCAD) is a rare cause of acute coronary syndrome or sudden death. SCAD has a high incidence in a younger, female population with an association with peripartum or postpartum status. Connective tissue disorders and vasculitides are also associated with SCAD. The purpose of this poster will be to examine the presentation and risk factors associated with SCAD and to discuss optimal treatment strategies.