Author Interviews, End of Life Care, JAMA, Race/Ethnic Diversity, UCSF / 02.11.2016
Minorities Much Less Likely To Have Advance Care Health Planning
MedicalResearch.com Interview with:
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Dr. Krista Lyn Harrison[/caption]
Krista Lyn Harrison, PhD
Division of Geriatrics School of Medicine
University of California
San Francisco VA Medical Center
San Francisco, CA 94121
MedicalResearch.com: What is the background for this study?
Response: Advance care planning (ACP) is the process of discussing plans and preferences for end-of-life care. It may include completion of advanced directives or a living will and designation of a surrogate decision-maker in a durable power of attorney for health care. There is a growing awareness of the benefits of such discussions for both elders and their families. In absence of these discussions, loved ones are left to guess what the affected individual wanted or may even get mired in unexpected legal issues. But until recently, it was unknown if all races/ethnicities, education levels, and incomes have benefited from efforts to improve engagement in advance care planning, and if these discussions are greater among those in worse health and with a poorer prognosis.
Dr. Krista Lyn Harrison[/caption]
Krista Lyn Harrison, PhD
Division of Geriatrics School of Medicine
University of California
San Francisco VA Medical Center
San Francisco, CA 94121
MedicalResearch.com: What is the background for this study?
Response: Advance care planning (ACP) is the process of discussing plans and preferences for end-of-life care. It may include completion of advanced directives or a living will and designation of a surrogate decision-maker in a durable power of attorney for health care. There is a growing awareness of the benefits of such discussions for both elders and their families. In absence of these discussions, loved ones are left to guess what the affected individual wanted or may even get mired in unexpected legal issues. But until recently, it was unknown if all races/ethnicities, education levels, and incomes have benefited from efforts to improve engagement in advance care planning, and if these discussions are greater among those in worse health and with a poorer prognosis.
Dr. Phillip Coffin[/caption]
Phillip O. Coffin, MD, MIA
Director of Substance Use Research
San Francisco Department of Public Health
Assistant Professor, Division of HIV, ID & Global Health
University of California, San Francisco
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: San Francisco has a longstanding naloxone distribution program that primarily works out of syringe exchange programs and is temporally associated with a substantial decline in opioid overdose death due to heroin or involving injection drug use. Over 90% of opioid overdose deaths from 2010-2012 were due to prescription opioids in the absence of heroin, and most of those decedents were prescribed opioids in primary care settings. Based on these data, as well as anecdotal reports from sites such as U.S. Army Fort Bragg in North Carolina - where providing naloxone to pain patients appeared to be associated with a radical decline in opioid overdose admissions to the emergency department - we implemented a naloxone prescribing program in the safety net primary care clinics.
We recommended that providers offer naloxone to all patients who used opioids on a regular basis, or were otherwise at risk for experiencing or witnessing an opioid overdose, although we only measured outcomes related to patients who were prescribed opioids for chronic pain. We also recommended that providers avoid the term "overdose" as that term does not properly reflect the epidemiology of opioid poisoning and is interpreted by many to mean intentionally consuming a large amount of opioids; instead we recommended saying things like: "Opioids can cause bad reactions where you stop breathing or can't be woken up." Providers prescribed mostly the jerry-rigged nasal device, with the atomizer and a brochure dispensed at clinic and the naloxone picked up at the patients' usual pharmacies, to approximate real-world medical practice.
Dr. Gregory Marcus[/caption]
Gregory M Marcus, MD, MAS, FACC, FAHA, FHRS
Director of Clinical Research
Division of Cardiology
Endowed Professor of Atrial Fibrillation Research
University of California, San Francisco
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: We and others have previously demonstrated that, despite the observation that African Americans on average exhibit more risk factors for atrial fibrillation, they demonstrate a substantially reduced risk of the disease. This suggests that, if we could understand the mechanism underlying this apparent paradox, we might learn something fundamentally important to atrial fibrillation that would be relevant to treating or preventing the disease regardless of race.
Building on our previous work demonstrating that, among African Americans, more European ancestry (determined by genomic testing) was a statistically significant predictor of atrial fibrillation, we sought to identify the gene(s) that might underlie this observation. The analysis took two forms.
First, we examined if any differences among several well-established single nucleotide polymorphisms (SNP) associated with atrial fibrillation might mediate the race-atrial fibrillation relationship. One such SNP statistically mediated (rs10824026) up to about a third of the race-atrial fibrillation relationship. It’s important to mention that a causal relationship cannot be proven here.
Perhaps more remarkable was the observation that the disease-associated alleles of the SNPs most closely associated with atrial fibrillation in multiple studies were actually significantly more common among African Americans, pointing to the complex nature of both the race-atrial fibrillation relationship as well as the genetics of atrial fibrillation.
Finally, leveraging the ancestral relationships, we performed a genome wide admixture mapping study with the hope of reducing the penalty for multiple hypothesis testing incurred in conventional genome wide association studies. While several loci revealed associations with atrial fibrillation with small p values, none met our criteria for genome wide significance.
Dr. Peter Ganz[/caption]
Peter Ganz, MD
Chief, Division of Cardiology
Director, Center of Excellence in Vascular Research
Zuckerberg San Francisco General Hospital
Maurice Eliaser Distinguished Professor of Medicine
University of California, San Francisco
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Ganz: The research described in the JAMA paper involved measuring 1,130 different proteins in nearly 2000 individuals with apparently stable coronary heart disease, who were followed up to 11 years. Initially, two hundred different proteins were identified whose blood levels could be related to the risk of heart attacks, strokes, heart failure and death, and ultimately a combination of nine proteins was selected for a risk prediction model, based on their combined accuracy and sensitivity.
Application of these findings to samples of patients with stable coronary heart disease demonstrated that some of those who were deemed clinically stable instead had a high risk of adverse cardiovascular outcomes, while other patients with the same clinical diagnosis had a very low risk. Thus, individuals who all carried the same clinical diagnosis of stable coronary heart disease had a risk of an adverse cardiovascular event that varied by as much as 10-fold, as revealed by analysis of the levels of the nine proteins in their blood. Given such large differences in risk and outcomes, patients could reasonably opt to be treated differently, depending on their level of risk. We hope that in the future, management of patients with stable angina will at least in part rely on risk assessment based on levels of blood proteins.
Dr. Jack Resneck[/caption]
Jack Resneck, Jr, MD
Professor and Vice-Chair of Dermatology
Core Faculty, Philip R. Lee Institute for Health Policy Studies
UCSF School of Medicine
MedicalResearch.com: What is the background for this study?
What are the main findings?
Dr. Resneck: Telemedicine, when done right, can improve access and offer convenience to patients. We have seen proven high-quality care in telemedicine services where patients are using digital platforms to communicate with their existing doctors who know them, and where doctors are getting teleconsultations from other specialists about their patients. But our study shows major quality problems with the rapidly growing corporate direct-to-consumer services where patients send consults via the web or phone apps to clinicians they don’t know.
Most of these sites aren’t giving patients a choice of the clinician who will care for them or disclosing the credentials of those clinicians – patients should know whether their rash is being cared for by a board-certified dermatologist, a pain management specialist, or a nurse practitioner who usually works in an emergency department. Some of these sites are even using doctors who aren’t licensed in the US. We also found that these sites were regularly missing important diagnoses, and prescribing medications without discussing risks and side-effects, putting patients at risk. We observed that if you upload photos of a highly contagious syphilis rash but state that you think you have psoriasis, most clinicians working for these direct-to-consumer sites will just agree with your self-diagnosis and prescribe psoriasis medications, leaving you with a contagious STD.
Perhaps the biggest problem with many of these sites is the lack of coordinating care for patients – most of them didn’t offer to send records to a patient’s existing local doctors. And when patients end up needing in-person care if their condition worsens, or they have a medication side-effect, those distant clinicians often don’t have local contacts, and are unable to facilitate needed appointments.
Dr. Jennifer Graves[/caption]
Jennifer Graves, MD, PhD, MAS
Adult and Pediatric Multiple Sclerosis Centers
UCSF
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Graves: Cessation of medications with effects on immune trafficking may be more likely to cause rebound inflammatory activity in autoimmune diseases such as multiple sclerosis. We observed 5 strikingly severe relapses consistent with rebound events following cessation of fingolimod treatment and identified several similar cases in the literature. At our center the rebound events occurred with an approximate 10% frequency.
MedicalResearch.com: What should clinicians and patients take away from your report?
Dr. Graves: Fingolimod cessation may be complicated by rebound phenomena in some patients, similar to what has been observed with natalizumab. Both of these medications have effects on immune cell trafficking, likely explaining the association with rebound events. Careful consideration must be taken in stopping these medications.
Dr. Rachael Callcut[/caption]
MedicalResearch.com Interview with:
Dr. Rachael Callcut M.D., M.S.P.H
Dr. Shinkai[/caption]
MedicalResearch.com Interview with:
Kanade Shinkai, MD PhD
Associate Professor of Clinical Dermatology
Director, Residency Program
Endowed Chair in Dermatology Medical Student Education
UCSF Department of Dermatology
San Francisco, CA 94115
Medical Research: What is the background for this study? What are the main findings?
Dr. Shinkai: Polycystic Ovary Syndrome (PCOS) is a common endocrine disorder in the United States that has important skin manifestations including acne, hair loss, hirsutism, and acanthosis nigricans. We performed a retrospective cross-sectional study of women referred to a multidisciplinary PCOS clinic at UCSF to determine whether skin findings and systemic associations differ between women who meet diagnostic criteria for PCOS versus those suspected of having PCOS but do not meet diagnostic criteria. We found that women with PCOS commonly have skin findings, however, present across a broad spectrum of cutaneous manifestations.
Comparing the skin findings in women who meet diagnostic criteria for PCOS with women who are suspected of having PCOS suggests that it can be very difficult to distinguish a patient with PCOS based on skin findings alone. Hirsutism and acanthosis nigricans are the most helpful findings to suggest 
Dr. Chao[/caption]
MedicalResearch.com Interview with:
Maria T. Chao, DrPH, MPA
Assistant Professor of Medicine
Osher Center for Integrative Medicine
& Division of General Internal Medicine - SFGH
UCSF
San Francisco, CA 94143-1726
Medical Research: What is the background for this study? What are the main findings?
Dr. Chao: Many Americans use complementary and integrative health (CIH) approaches to help them manage the symptoms of chronic diseases. To date, most of these treatments are only available in outpatient clinics. In this study, we asked oncology inpatients which of 12 different CIH approaches they currently use or have tried in the past, and also which approaches they would like to be available in the hospital. We found that 95% of patients had tried at least one complementary and integrative health approach in the past, and that a similarly high number were interested in accessing these services as an inpatient. More than three quarters of our sample expressed interest in receiving nutritional counseling and massage during their hospital stay, and approximately half were interested in acupuncture, biofeedback, and 
Dr. Gersing[/caption]
MedicalResearch.com Interview with:
Alexandra S. Gersing, MD
Department of Radiology and Biomedical Imaging
University of California, San Francisco
Medical Research: What is the background for this study? What are the main findings?
Dr. Gersing: This study is part of a larger NIH-funded project focusing on the effects of weight change in individuals at risk for and with osteoarthritis. Our group has previously shown that weight gain causes substantial worsening of knee joint degeneration in patients with risk factors for osteoarthritis and now we aimed to show that weight loss could protect the knee joint from degeneration and osteoarthritis. Osteoarthritis is one of the major causes of pain and disability worldwide; and cartilage plays a central role in the development of joint degeneration. Since cartilage loss is irreversible, we wanted to assess whether lifestyle interventions, such as weight loss, could make a difference at a very early, potentially reversible stage of cartilage degradation and whether a certain amount of weight loss is more beneficial to prevent cartilage deterioration. To measure these early changes we used a novel Magnetic Resonance Imaging (MRI) technique, called T2 mapping, which allows us to evaluate biochemical cartilage degradation in the patient on a molecular level. The most relevant finding of this study is that patients with more that 10% of 
Dr. Elsa Suberbielle[/caption]
MedicalResearch.com Interview with:
Elsa Suberbielle, DVM, PhD
Research Scientist
Gladstone Institute of Neurological Diseases
San Francisco, CA 94158
Medical Research: What is the background for this study?
Dr. Suberbielle: BRCA1 is a key protein involved in DNA repair, and mutations that impair its function increase the risk for breast and ovarian cancer. Research into DNA repair mechanisms in dividing cells recently was recently rewarded by the Nobel Prize in Chemistry. In such cells, BRCA1 helps repair a type of DNA damage known as double-strand breaks that can occur when cells are injured. In neurons, though, such breaks can occur even under normal circumstances, for example, after increased brain activity, as shown by the team of Gladstone scientists in an 
Dr. Ratanawongsa[/caption]
MedicalResearch.com Interview with:
Neda Ratanawongsa, MD, MPH
CMIO for CareLinkSF
Associate Professor, Division of General Internal Medicine
UCSF Center for Vulnerable Populations
Physician, Richard H. Fine People's Clinic (RHPC)
San Francisco, CA 94110
Medical Research: What is the background for this study?
Dr. Ratanawongsa: Many people are concerned about the growing intrusion of computers into the patient-provider relationship. Touted as systems that will make care safer and more cost-effective, electronic health records (EHRs) have proliferated rapidly across the country, fueled by HITECH funding. However, some health care professionals feel like computers keep them from connecting with their patients. Also prior research has shown that computer use can change communication in the exam room and shift agenda from patients' concerns toward medical talk.
Safety net patients already face communication barriers in routine care, particularly language and literacy barriers. Although EHRs could help improve care and communication with these vulnerable patients by helping clinicians fill in the gaps (e.g., what happened in the ED, what medication were you given by that specialist), EHRs could also worsen communication by drawing clinicians' focus away from patients during visits.
Dr. Bastian[/caption]
MedicalResearch.com Interview with:
Boris C. Bastian, MD, PhD
Professor of Dermatology and Pathology
Gerson and Barbara Bass Bakar Distinguished Professor in Cancer Research
University of California, San Francisco
Medical Research: What is the background for this study? What are the main findings?
Dr. Bastian: The cost of DNA sequencing has dropped substantially since the initial sequencing of the human genome in 2001. As a result, the most common cancer subtypes have now been sequenced, revealing the pathogenic mutations that drive them. A typical cancer is driven by 5-10 mutations, but we still do not understand the order in which these mutations occur for most cancers.
Determining the order in which mutations occur is challenging for cancers that are detected at a late stage. Melanomas, however, lend themselves to this type of analysis because they are pigmented and found on the surface of the skin, allowing them to be identified early. Sometimes, melanomas are even found adjacent to their remnant precursor neoplasms, such as benign nevi (also known as common moles). We performed detailed genetic analyses of 37 cases of melanomas that were adjacent to their intact precursor neoplasms. We microdissected and sequenced the surrounding uninvolved normal tissue, the precursor neoplasm, and the descendent neoplasm. By comparing the genetic abnormalities in each of the microdissected areas, we were able to decipher the order of genetic alterations for each case.
Our work reveals the stereotypic pattern of mutations as they occur in melanoma. Mutations in the MAPK pathway, usually affecting BRAF or NRAS, occur earliest, followed by TERT promoter mutations, then CDKN2Aalterations, and finally TP53 and PTEN alterations. Benign nevi typically harbor a single pathogenic alteration, whereas fully evolved melanomas harbor three or more pathogenic alterations. We also identified an intermediate stage of neoplasia with some but not all of the pathogenic mutations required for fully evolved melanoma. There has been a longstanding debate whether morphologically intermediate lesions, such as dysplastic nevi, truly constitute biological intermediates or whether they simply represent a gray zone of histopathological assessment. Our data indicates that these neoplasms are genuine biological entities. Finally, we observe evidence of UV-radiation-induced DNA damage at all stages of pathogenesis, implicating UV radiation in both the initiation and progression of melanoma.
