Ari Hoffman

Tissue distribution of surfactant proteins A and D in the mouse.

Surfactant proteins A and D, collagen-like lectins (collectins), were first isolated from the lung. In the lung, SP-A and SP-D have roles in surfactant homeostasis and innate immunity. In this study we show that SP-A and SP-D mRNA can be detected in a significant number of non-pulmonary tissues but the proteins have a more limited distribution. SP-D protein was detected in lung, uterus, ovary, and lacrimal gland, whereas SP-A protein was detected only in the lung. The results suggest that SP-D participates in mucosal immunity throughout the body.

Cellular and molecular mechanism regulating blood flow recovery in acute versus gradual femoral artery occlusion are distinct in the mouse

BACKGROUND Most current animal models of hindlimb ischemia use acute arterial occlusion that does not accurately reflect the pathogenesis of gradual arterial occlusion in humans. We, therefore, developed the first mouse model of gradual arterial occlusion and tested the hypothesis that the mechanisms regulating blood flow recovery are critically dependent on the rate of arterial occlusion. METHODS Gradual arterial occlusion was induced by placing ameroid constrictors on the proximal and distal left femoral artery, and ligating the femoral arterial branches (n = 36). Acute arterial occlusion was accomplished by excising the left femoral artery (n = 36). The blood flow recovery was studied by laser Doppler imaging. Differential gene expression between these two models was assessed by quantitative real-time polymerase chain reactions (PCR). Inflammatory and progenitor cells recruitment were determined by immunohistochemistry. RESULTS We found that hypoxia-related genes increased significantly in the calf, but not in the thigh, after gradual and acute femoral arterial occlusion (P < .05). Shear-stress dependent genes and inflammatory genes were upregulated immediately in the thigh only after acute femoral arterial occlusion (P < .05). These differences in gene expression were consistent with increased SDF-1alpha expression, recruitment of macrophages and hemangiocytes, and higher blood flow recovery after acute arterial occlusion than after gradual arterial occlusion (P < .05). CONCLUSION This is the first study to show the mechanisms that regulate blood flow recovery are critically dependent on the rate of arterial occlusion. This novel model of gradual arterial occlusion may more closely resemble the human diseases, and may provide more accurate mechanistic insights for creating novel molecular therapies.

Improving medical student communication skills through improvisational theatre

Context and setting Developing strong communication skills is integral to becoming an effective health provider. In recent years good doctor–patient communication has been linked to improved patient satisfaction, better patient care and a decrease in malpractice lawsuits. Having recognised its importance, medical schools have strived to teach students not only the science of medicine, but also the art of communication. Unfortunately, creating methods for teaching communication skills that are effective and enjoyed by most students is challenging. Why the idea was necessary Our medical school teaches experiential communication skills to Year 1 and 2 students in the setting of patient interviews and standardised patient experiences with on-the-spot feedback. These methods, however, are imperfect. Real patient interviews can end up too focused on clinical matters. Standardised patient interviews are costly, often artificial, and typically performed under high-stress testing situations. The feedback given in these circumstances runs the risk of being overly specific to the observed interaction and peer feedback is often limited by the amount of student investment in the exercise. We sought to teach communication skills in an interactive environment with effective feedback driven by a concrete framework for discussing personal interactions. What was done Two students taught a quarter-long elective for Year 1 medical students with three themes: portraying ourselves; perception of others, and interpersonal interactions. The elective focused on exercises derived from improvisational theatre (improv). Practising improv teaches quick thinking, a valuable skill in the practice of medicine. Students actively participated in weekly improv exercises that coached specific skill sets: portraying varied social status; improving and directing attention; telling stories, and working as a team. The exercises themselves were not related to clinical scenarios. Instead, the tenets and vocabulary drawn from improv provided a structure for applying lessons learned in the communication exercises to the doctor–patient relationship. Each session included ample time for students to comment on what they saw and experienced in their performances , as well as how they could utilise their new skills in the clinical realm. A subset of sessions were led by improv experts as well as doctors who provided personal experience and clinical scenarios in which the students engaged in more traditional role play. Evaluation of results and impact End-of-course evaluations (n = 18) using a 5-point scale produced the following positive responses: that the course improved communication skills (mean 4.12); that it increased confidence in patient interactions (mean 4.01), and that it was worth repeating (mean 4.55). All participants responded that the course was enjoyable (mean 4.69). One student commented that improv storytelling helped with active listening and appreciating other people s train of thought . In a debriefing session, groups of students worked together to summarise the lessons of the course through improv exercises, stating that the course taught them to listen and be more human . By providing participants with a practical and fun approach to communication – as well as the vocabulary to discuss their interactions – the course created a more effective environment than traditional approaches to delving into the nuances of the doctor–patient interaction.

Reengineering US Health Care

Despite substantial improvement in imaging techniques over the past decade, clinicians have become increasingly reluctant to search for renal artery stenosis in patients with hypertension. A reason for refraining from a diagnostic trajectory is doubt as to whether treatment of atherosclerotic renal artery stenosis with angioplasty, with or without stent placement, confers any benefit to the patient. A meta-analysis of 3 small randomized trials showed only a modest effect of balloon angioplasty on blood pressure among patients with atherosclerotic renal artery stenosis and 50% or more luminal reduction.1 Although not designed for that purpose, the trials did not show any benefit of angioplasty for preservation of renal function. This observation was reinforced by a large randomized trial2 demonstrating that rates of renal events, major cardiovascular events, and death were similar in the group assigned to undergo revascularization in addition to optimal medical treatment compared with the control group that received medical treatment only. In addition, no significant between-group differences in systolic blood pressure were apparent, and revascularization was associated with 31 serious complications in 23 patients. According to many investigators, therefore, this trial indicates that curing renovascular hypertension is not currently possible.

Endothelial nitric oxide synthase affects both early and late collateral arterial adaptation and blood flow recovery after induction of hind limb ischemia in mice

OBJECTIVE The goals of this study were to determine if endothelial nitric oxide synthase (eNOS) affects both early and late collateral arterial adaptation and blood flow recovery after severe limb ischemia in a mouse model and to determine if eNOS-derived NO is necessary for recruitment of chemokine (C-X-C motif) receptor 4 (CXCR4)(+) vascular endothelial growth factor receptor-1 (VEGFR1)(+) hemangiocytes to the site of ischemia. METHODS Two studies were completed. In the first, hind limb ischemia was induced by unilateral femoral artery excision in three groups: C57Bl6 (wild-type), eNOS(-/-), and C57Bl/6 mice treated with N(G)-nitro-L-arginine methyl ester (L-NAME) from 1 day before excision through day 3 after excision (early L-NAME group). These groups were studied on day 3 after induction of ischemia. In the second study, hind limb ischemia was induced in C57Bl/6 mice (wild-type) and C57Bl/6 mice treated with L-NAME from days 3 through 28 after induction of ischemia. These groups were studied day 28 after ischemia induction. Dependent variables included hind limb perfusion, collateral artery diameter, and the number and location of hemangiocytes within the ischemic hind limb. RESULTS In the first study, toe gangrene developed in the eNOS(-/-) and early L-NAME treatment groups by day 2. These groups demonstrated less blood flow recovery and smaller collateral artery diameter than the wild-type group. Hemangiocytes were present within the adventitia of collateral arteries in the wild-type group but were only sparsely present, in a random pattern, in the eNOS(-/-) and early L-NAME treatment groups. In the second study, the late L-NAME group showed less blood flow recovery and smaller collateral artery diameter on day 28 of ischemia than the wild-type group. Hemangiocytes were present in a pericapillary distribution in the wild-type group, but were present only sparsely in the late L-NAME treatment group. CONCLUSION Early (day 3) and late (day 28) adaptive responses to hind limb ischemia both require eNOS-derived NO. NO is necessary for normal hemangiocyte recruitment to the ischemic tissue.

Disaster mobile health technology: lessons from Haiti.

INTRODUCTION Mobile health (mHealth) technology can play a critical role in improving disaster victim tracking, triage, patient care, facility management, and theater-wide decision-making. PROBLEM To date, no disaster mHealth application provides responders with adequate capabilities to function in an austere environment. METHODS The Operational Medicine Institute (OMI) conducted a qualitative trial of a modified version of the off-the-shelf application iChart at the Fond Parisien Disaster Rescue Camp during the large-scale response to the January 12, 2010 earthquake in Haiti. RESULTS The iChart mHealth system created a patient log of 617 unique entries used by on-the-ground medical providers and field hospital administrators to facilitate provider triage, improve provider handoffs, and track vulnerable populations such as unaccompanied minors, pregnant women, traumatic orthopedic injuries and specified infectious diseases. CONCLUSION The trial demonstrated that even a non-disaster specific application with significant programmatic limitations was an improvement over existing patient tracking and facility management systems. A unified electronic medical record and patient tracking system would add significant value to first responder capabilities in the disaster response setting.

Oral Tetrahydrobiopterin Improves the Beneficial Effect of Adenoviral-mediated eNOS Gene Transfer After Induction of Hindlimb Ischemia

We tested the hypothesis that oral supplementation with the endothelial nitric oxide synthase (eNOS) cofactor tetrahydrobiopterin (BH(4)) improved the therapeutic efficacy of eNOS gene transfer in the ischemic rat hindlimb. BH(4) or vehicle were begun 1 week before induction of hindlimb ischemia, whereas recombinant adenovirus containing bovine eNOS cDNA (AdeNOS) or vehicle [phosphate-buffered saline (PBS)] was infused intra-arterially into the ischemic hindlimb 10 days after induction of ischemia. Rats receiving co-treatment with dietary BH(4) and eNOS gene transfer (the [eNOS, +BH(4)] group) had greater eNOS expression, phospho-eNOS expression (Ser(1177)), Ca(2+)-dependent NOS activity, and nitrite + nitrate concentrations in the ischemic gastrocnemius than did rats receiving AdeNOS alone. The [eNOS, +BH(4)] group demonstrated less nitrotyrosine and a higher ratio of reduced:oxidized glutathione (GSH:GSSG) in the ischemic gastrocnemius muscle than did rats receiving AdeNOS alone. The [eNOS, +BH(4)] group had greater flow recovery and a higher capillary:myocyte ratio in the ischemic hindlimb than did rats receiving AdeNOS alone. Finally, the [eNOS,+BH(4)] group had less necrosis of hindlimb muscles than rats given AdeNOS alone. We conclude that adjunctive dietary therapy with BH(4) increases the beneficial effects of eNOS gene transfer within the ischemic gastrocnemius muscle, as evidenced by increased nitric oxide (NO) production, diminished oxidative stress, enhanced flow recovery, and reduced necrosis.

Varying Charges and Questionable Costs

Varying Charges and Questionable Costs Ari B. Hoffman, MD 1 and Andrew B. Bindman, MD 2,3 Department of Medicine, UCSF Medical Center, University of California San Francisco, San Francisco, CA, USA; 2 Departments of Medicine and Epidemiology & Biostatistics, San Francisco General Hospital, University of California San Francisco, San Francisco, CA, USA; 3 Philip R. Lee Institute for Health Policy Studies, University of California San Francisco, San Francisco, CA, USA. J Gen Intern Med 30(11):1579–80 DOI: 10.1007/s11606-015-3454-8

Capsule Commentary on O’Malley et al., Providers’ Experiences with Chronic Care Management (CCM) Services and Fees: A Qualitative Research Study

T his qualitative study by O’Malley et al. explores the current state of chronic care management (CCM) in a variety of practice settings. The investigators conducted semi-structured interviews of providers who bill the Centers for Medicare and Medicaid Services (CMS) for CCM, those who do not, and professional society representatives in order to elucidate the perceived facilitating factors, barriers, successes, and failures of the federal payment policy for the important disease management work done outside of office visits. Their findings reveal critical limitations in the CCM payment policy, even after the 2017 amendments. For context, we know that CCM, done right, can decrease hospitalization and ED visits over time, with an estimated

How Best To Engage Patients, Doctors, And Other Stakeholders In Designing Comparative Effectiveness Studies

101-per-participant reduction in Medicare spending. We also know that proper implementation of CCM, like anything else, takes time andmoney. Reimbursement for CCM by CMS is a step in the right direction, but uptake in the early years of the policy is incredibly low, with fewer than 5% of all eligible providers billing CCM. This study sheds light on why. The study findings are limited by the small number of nonbilling providers interviewed, but the results highlight the limitations of the CCM policy itself. Documentation burdens and active billing (as opposed to per-member/per-month payments used in patient-centered medical home models) create barriers to entry for providers. Worse, patient eligibility restrictions and coinsurance payments are barriers for patients. We know from the 40-year old RAND health insurance experiment that patient cost sharing leads to decreased utilization of even highly effective services, and cost sharing was indeed highlighted as a barrier for those without supplemental coverage. One in seven Medicare beneficiaries have no supplemental coverage, and they are disproportionately black, poor, and disabled. Not only is the coinsurance ineffective at achieving the goal, but it contributes to health inequity. Taken together, these findings suggest that further improvements in the CCM payment policy that reduce barriers to uptake and ensure best practices have the potential to reduce costly utilization, improve outcomes, and save money, the holy grail of healthcare value.