Hypertension update, JNC8 and beyond.

Hypertension is the most preventable major risk factor for cardiovascular morbidity and mortality. The etiology of elevated blood pressure is a complex process involving the interaction of genetics, demographics, comorbid disorders, and environmental influences. Effective hypertensive therapy has been shown to reduce cardiovascular morbidity and mortality. JNC reports have served as a valuable source of guidelines, and JNC 8 is the most recently updated guideline for the prevention, diagnosis, and treatment of hypertension. It includes modification of JNC 7 regarding the threshold for therapy, therapeutic goals, and medications or combinations of medications that differ in benefits for certain patient populations. However, JNC 8 generated a significant degree of controversy. This review will evaluate JNC 7 versus JNC 8 guidelines and discuss the most controversial aspects of JNC 8 through a therapeutic perspective. This review will also discuss the most recently available evidence that has an impact on the JNC 8 recommendations. Despite the nuance of clinical guidelines, blood pressure control rates remains suboptimal. We will explore potential reasons and solutions for this dilemma including pharmacogenomics, novel risk-stratification strategies, lifestyle interventions, and integrative care.

Radiation-induced breast cancer: the question of early breast cancer screening in Hodgkin's lymphoma survivors.

Chest irradiation is associated with numerous early and late complications that arise from ionizing radiation-induced damage to cellular structures within the field of therapy. In patients exposed to chest irradiation at an early age as part of the treatment of childhood cancer, specifically Hodgkin's lymphoma, the increased risk of breast cancer in the long run should be considered. A case of a 35-year-old woman who exposed to chest irradiation as part of the treatment of Hodgkin's lymphoma at the age of 20 years is presented here and serves as a reminder of this somewhat overlooked complication. The article presents the evidence available for and against breast cancer screening in this particular patient population.

Teaching Medical Students to Help Patients Quit Smoking: Outcomes of a 10-School Randomized Controlled Trial.

BACKGROUND: Early in medical education, physicians must develop competencies needed for tobacco dependence treatment. OBJECTIVE: To assess the effect of a multi-modal tobacco dependence treatment curriculum on medical students' counseling skills. DESIGN: A group-randomized controlled trial (2010-2014) included ten U.S. medical schools that were randomized to receive either multi-modal tobacco treatment education (MME) or traditional tobacco treatment education (TE). SETTING/PARTICIPANTS: Students from the classes of 2012 and 2014 at ten medical schools participated. Students from the class of 2012 (N = 1345) completed objective structured clinical examinations (OSCEs), and 50 % (N = 660) were randomly selected for pre-intervention evaluation. A total of 72.9 % of eligible students (N = 1096) from the class of 2014 completed an OSCE and 69.7 % (N = 1047) completed pre and post surveys. INTERVENTIONS: The MME included a Web-based course, a role-play classroom demonstration, and a clerkship booster session. Clerkship preceptors in MME schools participated in an academic detailing module and were encouraged to be role models for third-year students. MEASUREMENTS: The primary outcome was student tobacco treatment skills using the 5As measured by an objective structured clinical examination (OSCE) scored on a 33-item behavior checklist. Secondary outcomes were student self-reported skills for performing 5As and pharmacotherapy counseling. RESULTS: Although the difference was not statistically significant, MME students completed more tobacco counseling behaviors on the OSCE checklist (mean 8.7 [SE 0.6] vs. mean 8.0 [SE 0.6], p = 0.52) than TE students. Several of the individual Assist and Arrange items were significantly more likely to have been completed by MME students, including suggesting behavioral strategies (11.8 % vs. 4.5 %, p < 0.001) and providing information regarding quitline (21.0 % vs. 3.8 %, p < 0.001). MME students reported higher self-efficacy for Assist, Arrange, and Pharmacotherapy counseling items (ps ≤0.05). LIMITATIONS: Inclusion of only ten schools limits generalizability. CONCLUSIONS: Subsequent interventions should incorporate lessons learned from this first randomized controlled trial of a multi-modal longitudinal tobacco treatment curriculum in multiple U.S. medical schools. NIH Trial Registry Number: NCT01905618.

Risking Life and Limb: A Case of Spontaneous Diabetic Muscle Infarction (Diabetic Myonecrosis).

Diabetic muscle infarction, also known as diabetic myonecrosis, is a microvascular complication of poorly controlled diabetes mellitus characterized by unilateral limb pain and swelling. Because these symptoms closely mimic cellulitis and thromboembolism, diagnosis is often delayed or missed altogether, leading to increased morbidity and inappropriate treatment. We describe a case of unilateral limb pain and swelling due to diabetic muscle infarction in a 36-year-old patient with poorly controlled diabetes mellitus. We also review the literature on the diagnosis, prognosis, and management of this under-recognized condition.

The relative influence of apatite crystal orientations and intracortical porosity on the elastic anisotropy of human cortical bone.

Elastic anisotropy exhibits spatial inhomogeneity in human cortical bone, but the structural origins of anatomic variation are not well understood. In this study, the elastic anisotropy of human cortical bone was predicted using a specimen-specific multiscale model that investigated the relative influence of apatite crystal orientations and intracortical porosity. The elastic anisotropy of cortical bone specimens from the diaphysis of human femora was measured by ultrasonic wave propagation as the ratio of elastic constants in the longitudinal/radial (L/R) and longitudinal/circumferential (L/C) anatomic specimen axes. Experimental measurements of elastic constants exhibited orthotropy, with greater anisotropy in the L/R plane compared to the L/C plane. Model predictions included (1) a micromechanical model accounting for the effects of apatite crystal orientations, (2) a voxel-based finite element model accounting for the effects of intracortical porosity, and (3) a combined model accounting for both effects. The combined model provided the most accurate predictions of elastic anisotropy in both the L/R and L/C plane, with less than 10% mean error. The micromechanical model alone was able to accurately predict elastic anisotropy in the L/C plane, but predicted transverse isotropy. The finite element model alone grossly underestimated elastic anisotropy in both the L/R and L/C planes, but was able to predict orthotropy. Therefore, the results of this study suggest that the dominant and less variable transverse isotropy of human cortical bone, reflected by L/C, is governed primarily by apatite crystal orientations, while the more subtle and variable orthotropy, reflected by the difference between L/R and L/C, is governed primarily by intracortical porosity. Moreover, the combined model may be useful to investigate other structure-function relationships or in place of current numerical models, for example, in the study of bone adaptation and metabolic bone disease.

Anatomic variation in the elastic inhomogeneity and anisotropy of human femoral cortical bone tissue is consistent across multiple donors.

Numerical models commonly account for elastic inhomogeneity in cortical bone using power-law scaling relationships with various measures of tissue density, but limited experimental data exists for anatomic variation in elastic anisotropy. A recent study revealed anatomic variation in the magnitude and anisotropy of elastic constants along the entire femoral diaphysis of a single human femur (Espinoza Orías et al., 2009). The objective of this study was to confirm these trends across multiple donors while also considering possible confounding effects of the anatomic quadrant, apparent tissue density, donor age, and gender. Cortical bone specimens were sampled from the whole femora of 9 human donors at 20%, 50%, and 80% of the total femur length. Elastic constants from the main diagonal of the reduced fourth-order tensor were measured on hydrated specimens using ultrasonic wave propagation. The tissue exhibited orthotropy overall and at each location along the length of the diaphysis (p < 0.0001). Elastic anisotropy increased from the mid-diaphysis toward the epiphyses (p < 0.05). The increased elastic anisotropy was primarily caused by a decreased radial elastic constant (C(11)) from the mid-diaphysis toward the epiphyses (p < 0.05), since differences in the circumferential (C(22)) and longitudinal (C(33)) elastic constants were not statistically significant (p > 0.29). Anatomic variation in intracortical porosity may account for these trends, but requires further investigation. The apparent tissue density was positively correlated with the magnitude of each elastic constant (p < 0.0001, R(2) > 0.46), as expected, but was only weakly correlated with C(33)/C(11) (p < 0.05, R(2) = 0.04) and not significantly correlated with C(33)/C(22) and C(11)/C(22).

Improved accuracy of cortical bone mineralization measured by polychromatic microcomputed tomography using a novel high mineral density composite calibration phantom.

PURPOSE: Microcomputed tomography (micro-CT) is increasingly used as a nondestructive alternative to ashing for measuring bone mineral content. Phantoms are utilized to calibrate the measured x-ray attenuation to discrete levels of mineral density, typically including levels up to 1000 mg HA/cm3, which encompasses levels of bone mineral density (BMD) observed in trabecular bone. However, levels of BMD observed in cortical bone and levels of tissue mineral density (TMD) in both cortical and trabecular bone typically exceed 1000 mg HA/cm3, requiring extrapolation of the calibration regression, which may result in error. Therefore, the objectives of this study were to investigate (1) the relationship between x-ray attenuation and an expanded range of hydroxyapatite (HA) density in a less attenuating polymer matrix and (2) the effects of the calibration on the accuracy of subsequent measurements of mineralization in human cortical bone specimens. METHODS: A novel HA-polymer composite phantom was prepared comprising a less attenuating polymer phase (polyethylene) and an expanded range of HA density (0-1860 mg HA/cm3) inclusive of characteristic levels of BMD in cortical bone or TMD in cortical and trabecular bone. The BMD and TMD of cortical bone specimens measured using the new HA-polymer calibration phantom were compared to measurements using a conventional HA-polymer phantom comprising 0-800 mg HA/cm3 and the corresponding ash density measurements on the same specimens. RESULTS: The HA-polymer composite phantom exhibited a nonlinear relationship between x-ray attenuation and HA density, rather than the linear relationship typically employed a priori, and obviated the need for extrapolation, when calibrating the measured x-ray attenuation to high levels of mineral density. The BMD and TMD of cortical bone specimens measured using the conventional phantom was significantly lower than the measured ash density by 19% (p < 0.001, ANCOVA) and 33% (p < 0.05, Tukey's HSD), on average, respectively. The BMD and TMD of cortical bone specimens measured using the HA-polymer phantom with an expanded range of HA density was significantly lower than the measured ash density by 8% (p < 0.001, ANCOVA) and 10% (p < 0.05, Tukey's HSD), on average, respectively. CONCLUSIONS: The new HA-polymer calibration phantom with a less attenuating polymer and an expanded range of HA density resulted in a more accurate measurement of micro-CT equivalent BMD and TMD in human cortical bone specimens compared to a conventional phantom, as verified by ash density measurements on the same specimens.

Student involvement on teaching rounds.

BACKGROUND: Inpatient internal medicine education occurs in a fragile learning environment. The authors hypothesized that when medical students are involved in teaching rounds, residents may perceive a decrease in value of attending teaching. METHOD: During two summer periods, trained research assistants shadowed teaching rounds, tracking patient census and team call status, recording basic content of rounds, and delivering a survey instrument to the learners, asking them to rate the quality of the attending's teaching that day. RESULTS: One hundred sixty-six rounds were analyzed. Attending teaching ratings peaked when students were highly involved. In fact, high student involvement was an independent predictor of higher resident evaluation of teaching rounds (P < .0001). CONCLUSIONS: The best teaching occurred when involvement of medical students was greatest and their involvement was not necessarily a zero-sum game. The authors conclude that attending investment in medical student education during teaching rounds benefits all members of the inpatient team.

Lessons from industry: one school's transformation toward "lean" curricular governance.

As medical education grapples with organizational calls for centralized curricular oversight, programs may be compelled to respond by establishing highly vertical, stacked governance structures. Although these models offer discrete advantages over the horizontal, compartmentalized structures they are designed to replace, they pose new challenges to ensuring curricular quality and the educational innovations that drive the curricula. The authors describe a hybrid quality-assurance (QA) governance structure introduced in 2003 at the University of Kentucky College of Medicine (UKCOM) that ensures centralized curricular oversight of the educational product while allowing individualized creative control over the educational process. Based on a Lean production model, this approach draws on industry experiences that strategically separate institutional accountability (management) for a quality curriculum from the decision-making processes required to ensure it (production). In so doing, the authors acknowledge general similarities and key differences between overseeing the manufacture of a complex product versus the education of a physician-emphasizing the structured, sequential, and measurable nature of each process. Further, the authors briefly trace the emergence of quality approaches in manufacturing and discuss the philosophical changes that accompany transition to an institutional governance system that relies on vigorous, robust performance measures to offer continuous feedback on curricular quality.

The Kentucky medical curriculum: continuing innovations in educating physicians.

The University of Kentucky College of Medicine (UKCOM) retains a long history of educational commitment, quality, and innovation. Since undergoing a major curricular revision in the early 1990s, the evolving UKCOM curriculum has continued to incorporate advances in biomedical knowledge and pedagogy while meeting changing societal needs and expectations for physicians in practice. Building upon its established record of excellence in medical education, a curricular quality assurance (QA) program has been initiated to more efficiently guide improvement and innovation by providing faculty with key resources to identify and disseminate local best practices in teaching, learning, and evaluation. Through such efforts, the University of Kentucky College of Medicine is committed to providing a rich educational experience that will meet the needs of students, physicians, and patients well into the 21st century.

Double-masked, placebo-controlled, randomized trial of lutein and antioxidant supplementation in the intervention of atrophic age-related macular degeneration: the Veterans LAST study (Lutein Antioxidant Supplementation Trial).

BACKGROUND: Age-related macular degeneration (ARMD) is the leading cause of vision loss in aging Westem societies. The objective of the lutein antioxidant supplementation trial (LAST) is to determine whether nutritional supplementation with lutein or lutein together with antioxidants, vitamins, and minerals, improves visual function and symptoms in atrophic ARMD. METHODS: The study was a prospective, 12-month, randomized, double-masked, placebo-controlled trial conducted at an urban midwestern Veterans Administration Hospital from August 1999 to May 2001. Ninety patients with atrophic ARMD were referred by ophthalmologists at two Chicago-area veterans medical facilities. Patients in Group 1 received lutein 10 mg (L); in Group 2, a lutein 10 mg/antioxidants/vitamins and minerals broad spectrum supplementation formula (L/A); and in Group 3, a maltodextrin placebo (P) over 12 months. RESULTS: In Groups 1 L and 2 L/A, mean eye macular pigment optical density increased approximately 0.09 log units from baseline, Snellen equivalent visual acuity improved 5.4 letters for Group 1 L and 3.5 letters for Group 2 L/A, and contrast sensitivity improved. There was a net subjective improvement in Amsler grid in Group 1 L. VFO-14 questionnaires conceming subjective glare recovery were nearly significant at 4 months for Group 2 L/A. Patients who received the placebo (Group 3) had no significant changes in any of the measured findings. CONCLUSION: In this study, visual function is improved with lutein alone or lutein together with other nutrients. Further studies are needed with more patients, of both genders, and for longer periods of time to assess long-term effects of lutein or lutein together with a broad spectrum of antioxidants, vitamins, and minerals in the treatment of atrophic age-related macular degeneration.

Urticaria, exanthems, and other benign dermatologic reactions to smallpox vaccination in adults.

A phase 1 smallpox vaccine trial involving 350 adult volunteers was conducted. Of these subjects, 250 were naive to vaccinia virus vaccine (i.e., "vaccinia naive"). Volunteers received a new cell-cultured smallpox vaccine or a live vaccinia virus vaccine. Nine self-limiting rashes (3.6%) were observed in the vaccinia-naive group. None of the vaccinia-experienced patients had a rash. Rashes appeared 6-19 days after vaccination and had 5 different clinical presentations. Five volunteers had urticarial rashes that resolved within 4-15 days, 1 had an exanthem that lasted 20 days, and 1 each presented with folliculitis, contact dermatitis, and erythematous papules found only on the hands and fingers. Volunteers reported pruritus, tingling, and occasional headaches. Relief was obtained with antihistamine and acetaminophen therapy. No volunteer experienced fever or significant discomfort.

Serum iron, transferrin saturation, ferritin, and dietary data in age-related macular degeneration.

Iron (Fe) is a tightly metabolically controlled mineral and growth factor for all living cells. Iron not bound in erythrocyte hemoglobin is transported by the plasma iron transport protein transferrin (Tf) and bound within cells by ferritin. Apo-Tf and apo-hemopexin are also known to be made locally in the retina. Free Fe is cytotoxic, promotes oxidation/lipid peroxidation, has been implicated as a risk factor in cardiac disease, and is itself associated with age-related macular degeneration (ARMD), the leading cause of blindness in aging western societies. The authors evaluated Fe overload serum markers and dietary intake in patients with atrophic ARMD. After obtaining informed consent, an Fe panel consisting of serum Fe, total Fe binding capacity (TIBC), and ferritin was performed on 75 veterans (70 men, five women) with an average age of 75 years with a diagnosis of atrophic ARMD by combined criteria of International Retinal Classification and psychophysical/symptom abnormalities. Tf saturation was calculated by dividing serum Fe concentration by TIBC. Dietary iron with and without supplementation and vitamin C intake were determined for 86 patients using the Harvard School of Public Health/Department of Nutrition Food Frequency Questionnaire. Statistically significant correlations (P <0.1) were found between serum and dietary Fe (r = -.26), between serum Fe and serum ferritin (r =.34), and between dietary Fe and dietary vitamin C (r =.30). The data on mostly male geriatric veterans with atrophic ARMD indicate that single time-point assessment of systemic Fe status and dietary Fe is not useful. However, serial multiple-year data, correlating Fe markers with disease, may still be important. Also, because Fe transport proteins do not cross the blood-retina barrier, the local cellular toxic effects of Fe must also be considered.

Renin Status in Association with Responsiveness to Behavioral Therapy in Hypertension.

This double-blind experiment tested the hypothesis that renin is a mediator of neurogenic hypertension. Forty-three of 46 hypertensive (mean BP 142/94) were typed for renin index and treated by combinations of group therapy (n = 32) or placebo (n = 11). A treatment effect in the therapy group resided virtually in the high/normal renin subset (21 subjects, mean drop 6/6 mm Hg, p <.05/ <.02), and was not present in the low renin subset (11 subjects, mean change minus sign3/1 mm Hg). The renin index fell in the high/normal therapy subset of the whole therapy group (from mean 217 to 159) while that of the low renin subset rose (mean 35 to 85) p, < 0.01. Results show that renin-driven essential hypertension is a form of neurogenic hypertension and is susceptible to behavioral therapeutic approaches. In this regard, it warrents further study for clinical recognition for early application of angiotensin inhibiters and beta-adrenergic blockade.