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2.  Renal Sympathetic Denervation in the Treatment of Resistant Hypertension 
Arterial hypertension (HTN) is a major health problem worldwide. Treatment-resistant hypertension (trHTN) is defined as the failure to achieve target blood pressure despite the concomitant use of maximally tolerated doses of three different antihypertensive medications, including a diuretic. trHTN is associated with considerable morbidity and mortality. Renal sympathetic denervation (RDn) is available and implemented abroad as a strategy for the treatment of trHTN and is currently under clinical investigation in the United States. Selective renal sympathectomy via an endovascular approach effectively decreases renal sympathetic nerve hyperactivity leading to a decrease in blood pressure. The Symplicity catheter, currently under investigation in the United States, is a 6-French compatible system advanced under fluoroscopic guidance via percutaneous access of the common femoral artery to the distal lumen of each of the main renal arteries. Radiofrequency (RF) energy is then applied to the endoluminal surface of the renal arteries via an electrode located at the tip of the catheter. Two clinical trials (Symplicity HTN 1 and Symplicity HTN 2) have shown the efficacy of RDn with a post-procedure decline of 27/17mmHg at 12 months and 32/12 mmHg at 6 months, respectively, with few minor adverse events. Symplicity HTN-3 study is a, multi-center, prospective, single-blind, randomized, controlled study currently under way and will provide further insights about the safety and efficacy of renal denervation in patients with trHTN.
PMCID: PMC4257026  PMID: 25506285
uncontrolled hypertension; treatment resistant hypertension; renal denervation; hypertension; vascular diseases; cardiovascular diseases
3.  ‘Poisonous, Filthy, Loathsome, Damnable Stuff’: The Rhetorical Ecology of Vaccination Concern 
In this article, we analyze newspaper articles and advertisements mentioning vaccination from 1915 to 1922 and refer to historical studies of vaccination practices and attitudes in the early 20th century in order to assess historical continuities and discontinuities in vaccination concern. In the Progressive Era period, there were a number of themes or features that resonated with contemporary issues and circumstances: 1) fears of vaccine contamination; 2) distrust of medical professionals; 3) resistance to compulsory vaccination; and 4) the local nature of vaccination concern. Such observations help scholars and practitioners understand vaccine skepticism as longstanding, locally situated, and linked to the sociocultural contexts in which vaccination occurs and is mandated for particular segments of the population. A rhetorical approach offers a way to understand how discourses are engaged and mobilized for particular purposes in historical contexts. Historically situating vaccine hesitancy and addressing its articulation with a particular rhetorical ecology offers scholars and practitioners a robust understanding of vaccination concerns that can, and should, influence current approaches to vaccination skepticism.
PMCID: PMC4257028  PMID: 25506275
vaccination; vaccine; immunization; smallpox; rhetorical ecology
4.  Understanding Vaccines: A Public Imperative 
Though once a discovery greatly celebrated by the nation, the vaccine has come under fire in recent decades from skeptics, critics, and a movement set into motion by fraudulent scientists and fueled by frustrated parents looking for answers to the autism conundrum. There is enough denialist resistance to vaccination to bring upon renewed fear of young children and infants becoming infected with diseases, the threats of which had been functionally eradicated from the United States. In more recent years, the surge in independent online journalism and blogging has invited many to rapidly share their opinions with millions of readers and, importantly, has appeared to open the door for opinion to be portrayed as fact. As a result, many parents are inundated with horror stories of vaccine dangers, all designed to eat away at them emotionally while the medical and scientific communities have mounted their characteristic response by sharing the facts, the data, and all of the reliable peer-reviewed and well-cited research to show that vaccines are safe and effective. It has become clear to me that facts are no match for emotion, but perhaps an understanding behind vaccine methodology will help parents overcome these fears of vaccinating. By helping those who doubt vaccines better understand what vaccines really are and how they work in such an incredibly engineered fashion, we may have a stronger weapon than we realize in battling the emotional arsenal that comes from the fear and skepticism of vaccinating.
PMCID: PMC4257029  PMID: 25506276
vaccines; anti-vaccination; public understanding
5.  Healthy Bodies, Toxic Medicines: College Students and the Rhetorics of Flu Vaccination 
This article examines flu vaccination beliefs and practices produced during a survey of undergraduate students in Spring 2012 (IRB#10-732). This research uses the methods of rhetorical analysis — or the study of persuasive features and arguments used in language — to examine statements respondents made regarding flu and flu vaccine. In these responses, students generated unique categories of arguments about the perceived dangers of flu vaccination, including the assertion that vaccines cause disease (including illnesses and conditions other than flu), that vaccines are toxic medicines, and that vaccines carry unknown, population-wide risks that are inadequately acknowledged. This study provides insight into vaccination beliefs and rationales among a population at risk of flu (college students) and suggests that further study of this population may yield important keys to addressing flu vaccine concerns as expressed by college students. Rhetorical analysis also offers a useful set of methods to understanding vaccination beliefs and practices, adding to existing methods of study and analysis of vaccination practices and beliefs in medicine and public health.
PMCID: PMC4257030  PMID: 25506277
influenza; flu vaccine; vaccination; rhetoric
6.  Improving Influenza Vaccination Coverage in the Pediatric Asthma Population: The Case for Combined Methodologies 
The Advisory Committee on Immunization Practices recommends annual influenza vaccine for pediatric asthma patients. Despite considerable risk for influenza complications in pediatric asthma patients, including hospitalization and death, influenza vaccination among children with asthma remains low, especially among low-income pediatric asthma patients. Multiple interventions have been attempted to increase immunization in the pediatric asthma population, including recall and reminders, parent/patient education, and physician education. More recently, information technology methods have been employed, including electronic alerts and computerized physician order entry/clinical decision support interventions. Each of these interventions, as well as a recent legislative intervention, has evidence of effectiveness, but none achieved the Healthy People 2020 vaccination goals of 80 percent for this population. This goal may be achievable with a combination of these methodologies and strategies that increase access to care for underserved patients.
PMCID: PMC4257031  PMID: 25506278
pediatric asthma patients; influenza vaccination; underserved patients; low-income pediatric patients; immunization rates; randomized controlled trials; computerized physician order entry; clinical decision support; legislation; recall and reminders; pediatric asthma hospitalizations for influenza; influenza prevention
7.  Pediatric Infectious Disease Epidemiology: Prevention Trumps Treatment 
PMCID: PMC4257032  PMID: 25506279
vaccines; influenza; pneumococcal vaccine; varicella; pediatric infectious disease; epidemiology
8.  Multilevel Factors Influencing Hepatitis B Screening and Vaccination among Vietnamese Americans in Atlanta, Georgia 
Chronic hepatitis B virus (HBV) infection may lead to liver cirrhosis, chronic liver disease, and liver cancer. Immunization rates are suboptimal among Asian Americans/Pacific Islanders (AAPIs), who remain disproportionately affected by these illnesses. We investigated socioecological factors affecting HBV prevention among 316 Vietnamese Americans in Atlanta, Georgia. Social and community support of HBV vaccination was associated with screening (OR=1.69, 95% CI [1.21,2.38]), vaccination (OR=1.89, [1.27,2.81]), and intent to vaccinate (OR=1.77, [1.13,2.78]). Misconceptions decreased screening likelihood (OR=0.67, [0.46,0.99]) and vaccination (OR=0.55, [0.35,0.86]). Those able to pay for medical treatment (OR=1.23, [1.01,1.50]) were also more likely immunized, and greater transportation access (OR=1.42, [1.07,1.87]) was associated with greater intention to vaccinate. Multi-level factors facilitated HBV vaccination in this population. Tailored, culturally appropriate communication strategies will positively influence immunization uptake.
PMCID: PMC4257033  PMID: 25506280
hepatitis B; vaccine acceptability; vaccine refusal; health disparities; community attitudes; community intervention; Asian Americans; Vietnamese American
9.  Reducing Outbreaks: Using International Governmental Risk Pools to Fund Research and Development of Infectious Disease Medicines and Vaccines 
The deadliest Ebola outbreak the world has ever seen is currently ravaging West Africa, despite the concerted efforts of the World Health Organization and many national governments. The current picture is troubling, but not altogether unexpected. Ebola was initially identified in 1976, and since that time, few drugs have been developed to combat it. The same is true for myriad other dangerous infectious diseases to which the world is currently susceptible. One proposal that might prevent outbreaks of this scale and magnitude from recurring would be to have the World Health Organization (WHO) and its technical partners assess which of its member states are at high risk for a disease, either directly or indirectly, and facilitate the creation of international governmental risk pools of those member states. Risk pools would offer open-indexed grant contracts to fund vaccine and drug development for a particular disease, and pharmaceutical companies could browse the index to apply for these grants. If the risk-pool states and a particular company sign a contract, a mutually agreed upon amount of the vaccine or drug would be produced at a below-market purchase price for those states. In return, the company would keep any patents or intellectual property rights for the developed vaccines or drugs. Risk-pool countries that did not use their vaccine or drug could resell that supply on secondary markets to other countries outside of the risk pool. This arrangement will increase the supply of tested drug and vaccine candidates available for combatting unexpected outbreaks of any previously discovered major infectious disease in the future.
PMCID: PMC4257034  PMID: 25506281
vaccine; drug; development; risk sharing; risk pools; economic; international
10.  Anti-Cancer Vaccines — A One-Hit Wonder? 
Immunization against common bacterial and viral diseases has helped prevent millions of deaths worldwide. More recently, the concept of vaccination has been developed into a potentially novel strategy to treat and prevent cancer formation, progression, and spread. Over the past few years, a handful of anti-cancer vaccines have been licensed and approved for use in clinical practice, thus providing a breakthrough in the field. However, the path has not always been easy, with many hurdles that have had to be overcome in order to reach this point. Nevertheless, with more anti-cancer vaccines currently in development, there is still hope that they can eventually become routine tools used in the treatment and prevention of cancer in the future. This review will discuss in detail both types of anti-cancer vaccine presently used in clinical practice — therapeutic and preventive — before considering some of the more promising anti-cancer vaccines that are currently in development. Finally, the issue of side effects and the debate surrounding the overall cost-effectiveness of anti-cancer vaccines will be examined.
PMCID: PMC4257035  PMID: 25506282
cancer immunotherapy; anti-cancer vaccines; therapeutic vaccines; preventive vaccines; personalized therapy
11.  Optimizing Dendritic Cell-Based Approaches for Cancer Immunotherapy 
Dendritic cells (DC) are professional antigen-presenting cells uniquely suited for cancer immunotherapy. They induce primary immune responses, potentiate the effector functions of previously primed T-lymphocytes, and orchestrate communication between innate and adaptive immunity. The remarkable diversity of cytokine activation regimens, DC maturation states, and antigen-loading strategies employed in current DC-based vaccine design reflect an evolving, but incomplete, understanding of optimal DC immunobiology. In the clinical realm, existing DC-based cancer immunotherapy efforts have yielded encouraging but inconsistent results. Despite recent U.S. Federal and Drug Administration (FDA) approval of DC-based sipuleucel-T for metastatic castration-resistant prostate cancer, clinically effective DC immunotherapy as monotherapy for a majority of tumors remains a distant goal. Recent work has identified strategies that may allow for more potent “next-generation” DC vaccines. Additionally, multimodality approaches incorporating DC-based immunotherapy may improve clinical outcomes.
PMCID: PMC4257036  PMID: 25506283
dendritic cell; immunotherapy; cancer; vaccine; combination therapy; chemotherapy
12.  Vaccine Development: How Scientific Collaboration and Communication Help Prevent the Spread of Disease 
PMCID: PMC4257037  PMID: 25506284
vaccines; Lyme disease; tick; OspA; immunity; infectious disease; vector-borne disease
13.  Anorectal Human Papillomavirus: Current Concepts 
Increased anorectal human papillomavirus (HPV) infection is related to the recent trends in sexual behavior in both homosexual and heterosexual groups and prevalence of infection with human immunodeficiency virus (HIV). Clinical presentation and natural history depend on the serotype involved. HPV 6 and 11 are found in the benign wart. Local control can be achieved with a wide selection of surgical and topical techniques. HPV 16, 18, and 31 are found in dysplastic lesions and have the potential to progress to invasive anal squamous cell carcinoma. Recognition and early management of dysplastic lesions is crucial to prevent the morbidity and mortality associated with anal cancer. While low-grade lesions can be closely observed, high-grade lesions should be eradicated. Different strategies can be used to eradicate the disease while preserving anorectal function. Studies on the efficacy of vaccination on anorectal HPV showed promising results in select population groups and led to the recent expansion of current vaccination recommendations.
PMCID: PMC4257038  PMID: 25506286
sexually transmitted diseases; human papillomavirus; anorectal infections; anal intraepithelial neoplasia; anal squamous cell carcinoma; sexual behavior; perianal disease; human papillomavirus vaccine; anal cytology
14.  The Controversy Surrounding Bone Morphogenetic Proteins in the Spine: A Review of Current Research 
Bone morphogenetic proteins have been in use in spinal surgery since 2002. These proteins are members of the TGF-beta superfamily and guide mesenchymal stem cells to differentiate into osteoblasts to form bone in targeted tissues. Since the first commercial BMP became available in 2002, a host of research has supported BMPs and they have been rapidly incorporated in spinal surgeries in the United States. However, recent controversy has arisen surrounding the ethical conduct of the research supporting the use of BMPs. Yale University Open Data Access (YODA) recently teamed up with Medtronic to offer a meta-analysis of the effectiveness of BMPs in spinal surgery. This review focuses on the history of BMPs and examines the YODA research to guide spine surgeons in their use of BMP in spinal surgery.
PMCID: PMC4257039  PMID: 25506287
spinal fusion; spine; postoperative complications; bone morphogenetic proteins
15.  Heart Block and Acute Kidney Injury Due to Hyperparathyroidism-Induced Hypercalcemic Crisis 
We describe a patient who presented with multi-system organ failure due to extreme hypercalcemia (serum calcium 19.8 mg/dL), resulting from primary hyperparathyroidism. He was found to have a 4.8 cm solitary atypical parathyroid adenoma. His course was complicated by complete heart block, acute kidney injury, and significant neurocognitive disturbances. Relevant literature was reviewed and discussed. Hyperparathyroidism-induced hypercalcemic crisis (HIHC) is a rare presentation of primary hyperparathyroidism and only a small minority of these patients develop significant cardiac and renal complications. In cases of HIHC, a multidisciplinary effort can facilitate rapid treatment of life-threatening hypercalcemia and definitive treatment by surgical resection. As such, temporary transvenous cardiac pacing and renal replacement therapy can provide a life-saving bridge to definitive parathyroidectomy in cases of HIHC.
PMCID: PMC4257040  PMID: 25506288
hyperparathyroidism; hypercalcemic crisis; heart block; acute kidney injury
16.  Lateralizing Sensorimotor Deficits in a Case of Pseudopheochromocytoma 
Pseudopheochromocytoma is a poorly understood, rare cause of severe paroxysmal hypertension that mimics the symptomatology of pheochromocytoma in the absence of biochemical evidence of this tumor. Symptoms such as headache, nausea, sweating, and palpitations during hypertensive episodes have been described. In this paper, we describe previously unreported findings of lateralizing sensorimotor deficits in a patient with pseudopheochromocytoma. These changes presented during a hypertensive episode and were concerning for stroke but were not accompanied by acute radiologic abnormalities. The deficits improved over 1.5 weeks as blood pressure stabilized with beta-blockade. We also review relevant literature on the clinical features, pathophysiology, and management of pseudopheochromocytoma.
PMCID: PMC4257041  PMID: 25506289
paroxysmal hypertension; pseudopheochromocytoma; labile blood pressure; stroke; case report
17.  A Comprehensive, Simulation-Based Approach to Teaching Clinical Skills: The Medical Students’ Perspective 
The purpose of this study was to determine if third-year medical students participating in a mandatory 12-week simulation course perceived improvement in decision-making, communication, and teamwork skills. Students participated in or observed 24 acute emergency scenarios. At 4-week intervals, students completed 0-10 point Likert scale questionnaires evaluating the curriculum and role of team leader. Linear contrasts were used to examine changes in outcomes. P-values were Bonferroni-corrected for multiple pairwise comparisons. Student evaluations (n = 96) demonstrated increases from week 4 to 12 in educational value (p = 0.006), decision-making (p < 0.001), communication (p = 0.02), teamwork (p = 0.01), confidence in management (p < 0.001), and translation to clinical experience (p < 0.001). Regarding the team leader role, students reported a decrease in stress (p = 0.001) and increase in ability to facilitate team function (p < 0.001) and awareness of team building (p = <0.001). Ratings demonstrate a positive impact of simulation on both clinical management skills and team leadership skills. A simulation curriculum can enhance the ability to manage acute clinical problems and translates well to the clinical experience. These positive perceptions increase as the exposure to simulation increases.
PMCID: PMC4257042  PMID: 25506290
medical education; simulation; communication skills
18.  On Medicaid and the Affordable Care Act in Connecticut 
Background: Medicaid is the federal program, administered by states, for health care for the poor. The Affordable Care Act (ACA) has added a large number of new recipients to this program.
Hypothesis: Medicaid programs in some, if not many, states do not provide patients uniform access to subspecialty care guaranteed by the federal statutes. Insofar as the ACA does not address this pre-existing “sub-specialty gap” and more patients are now covered by Medicaid under the ACA, the gap is likely to increase and may contribute to disparities of health care access and outcomes.
Methods: A brief description of previous studies demonstrating or suggesting a subspecialty gap in Medicaid services is accompanied by perspectives of the authors, using published literature — most notably the Denver, Colorado health care system — to propose various solutions that may be deployed to address gaps in subspecialty coverage.
Results: All published studies describing the Medicaid subspecialty gap are qualitative, survey designs. There are no authoritative objective data regarding the exact prevalence of gaps for each subspecialty in each state. However, surveys of caregivers suggest that gaps were prevalent in the United States prior to initiation of the ACA. Even fewer papers have addressed solutions (in light of the paucity of data describing the magnitude of the problem), and proposed solutions remain speculative and not grounded in objective data.
Conclusions: There is reason to believe that a substantial proportion of U.S. citizens — those who are guaranteed a full complement of health services through Medicaid — have difficult or no access to some subspecialty services, many of which other citizens take for granted. This problem deserves greater attention to verify its existence, quantify its magnitude, and develop solutions.
PMCID: PMC4257043  PMID: 25506291
Medicaid; health care; insurance; subspecialty care; justice
19.  The Future is Now: Frontiers on Display at Yale-NAVBO Cardiovascular Inflammation and Remodeling Symposium 2014 
Earlier this year, 200 researchers from across the globe gathered at the Omni New Haven Hotel at Yale University in New Haven, Connecticut, for 3 days of talks from 30 of the leading pioneers in modern cardiovascular medicine. From May 8 to 10, 2014, scientists discussed and dissected topics ranging from the clinical treatment of atherosclerosis to the molecular biology of leukocyte-endothelial cell interactions. With other sessions exploring vascular malformation and aneurysm, hypertension, the endothelial-mesenchymal transition (endo-MT), and the role of metabolism in cardiovascular disease, conference participants gained striking insights into rapid advances and ongoing challenges in the field of cardiovascular inflammation and remodeling.
PMCID: PMC4257044  PMID: 25506292
aneurysm; angiogenesis; atherosclerosis; Calabresi; cardiology; cardiomyopathy; cardiovascular; disease; endo-MT; endothelial; hypertension; inflammation; leukocyte; Loeys-Dietz; malformation; Marfan; mesenchymal; metabolism; NAVBO; PGC; PPCM; pulmonary; remodeling; symposium; transition; vascular; Yale
20.  Letter to the Editor 
PMCID: PMC4257045  PMID: 25506293
23.  Introduction 
PMCID: PMC4257027  PMID: 25647837
24.  Clinical Management of Patients Presenting with Non-Adjustable Gastric Band (NAGB) Complications 
Background: A number of bariatric surgical procedures have been developed to manage morbid obesity and related co-morbidities. The non-adjustable gastric band (NAGB) was one such procedure that created restriction to food intake by gastric segmentation. Benefits of the procedure included a low risk of perioperative complications and substantial early weight loss. Unfortunately, the long term results of NAGB include a high incidence of complications and failure to maintain weight loss. The purpose of this study was to examine the presentation, workup, and treatment of patients presenting with complications following NAGB placement.
Methods: A retrospective review of the diagnosis and management of 11 patients who presented with complications related to NAGB placement.
Results: All patients presented with some degree of proximal gastric outlet obstruction. The majority of patients (8/11) presented with vomiting as the main complaint. Other complaints included intolerance to solids, liquids, and reflux. Only 2/11 patients presented with weight loss since undergoing NAGB placement, while the remainder had weight regain to their pre-NAGB level and above. Depending on clinical presentation, desire for additional weight loss and co-morbid conditions, patients underwent a variety of treatments. This included NAGB removal (endoscopic, laparo-endoscopic, and laparoscopic) as well as conversion to another bariatric procedure (sleeve gastrectomy, Roux-en-Y gastric bypass).
Conclusion: Patients with NAGB complications present with symptoms related to a proximal gastric outlet obstruction, related to constriction imposed by the band. This may result in severe food and liquid intolerance and subsequent weight loss, but more likely results in maladaptive eating and subsequent weight gain. Optimal therapy involves removal of the NAGB. Laparoscopic conversion to another bariatric procedure, optimally a Roux-en-Y gastric bypass, is warranted to treat morbid obesity and associated co-morbidities.
PMCID: PMC4031789  PMID: 24910561
bariatric; complications; revision; laparoscopic; non-adjustable gastric band
25.  The Pathogenesis of Obesity from a Genomic and Systems Biology Perspective 
The recent obesity epidemic has imposed significant health, economical, and societal concerns. However, effective preventive and therapeutic strategies are currently lacking, primarily due to a lack of comprehensive understanding of the underlying molecular mechanisms. Recent genome-wide scans of genetic variants, transcriptome, and epigenome have uncovered >50 genetic loci that predispose individuals to obesity and revealed hundreds of genes with altered transcriptional activity and/or epigenetic variations in obesity-related tissues upon various environmental challenges such as high caloric diets, lack of physical activity, and environmental chemicals. These discoveries highlight the importance of genes involved in the control of energy homeostasis and food intake by the central nervous system, as well as genes contributing to lipid metabolism, adipogenesis, fat cell differentiation, and immune response in peripheral tissues, in obesity development. Future studies that are directed to obtain a more comprehensive, systems-level understanding of disease mechanisms and that test novel therapeutic strategies aiming at systems-level normalization of the obesity-related molecular alterations are warranted.
PMCID: PMC4031785  PMID: 24910557
obesity; genomics; genetic risks; environmental risks; high caloric diets; exercise; obesogen; transcriptome; epigenome; integrative genomics; systems biology

Results 1-25 (7383)