Peninsula Regional Medical Center

Despite signs of infection-including taste loss, dry mouth and mucosal lesions such as ulcerations, enanthema and macules-the involvement of the oral cavity in coronavirus disease 2019 (COVID-19) is poorly understood. To address this, we generated and analyzed two single-cell RNA sequencing datasets of the human minor salivary glands and gingiva (9 samples, 13,824 cells), identifying 50 cell clusters. Using integrated cell normalization and annotation, we classified 34 unique cell subpopulations between glands and gingiva. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral entry factors such as ACE2 and TMPRSS members were broadly enriched in epithelial cells of the glands and oral mucosae. Using orthogonal RNA and protein expression assessments, we confirmed SARS-CoV-2 infection in the glands and mucosae. Saliva from SARS-CoV-2-infected individuals harbored epithelial cells exhibiting ACE2 and TMPRSS expression and sustained SARS-CoV-2 infection. Acellular and cellular salivary fractions from asymptomatic individuals were found to transmit SARS-CoV-2 ex vivo. Matched nasopharyngeal and saliva samples displayed distinct viral shedding dynamics, and salivary viral burden correlated with COVID-19 symptoms, including taste loss. Upon recovery, this asymptomatic cohort exhibited sustained salivary IgG antibodies against SARS-CoV-2. Collectively, these data show that the oral cavity is an important site for SARS-CoV-2 infection and implicate saliva as a potential route of SARS-CoV-2 transmission.

BACKGROUND: Conventional dual-chamber pacing maintains atrioventricular synchrony but results in high percentages of ventricular pacing, which causes ventricular desynchronization and has been linked to an increased risk of atrial fibrillation in patients with sinus-node disease. METHODS: We randomly assigned 1065 patients with sinus-node disease, intact atrioventricular conduction, and a normal QRS interval to receive conventional dual-chamber pacing (535 patients) or dual-chamber minimal ventricular pacing with the use of new pacemaker features designed to promote atrioventricular conduction, preserve ventricular conduction, and prevent ventricular desynchronization (530 patients). The primary end point was time to persistent atrial fibrillation. RESULTS: The mean (+/-SD) follow-up period was 1.7+/-1.0 years when the trial was stopped because it had met the primary end point. The median percentage of ventricular beats that were paced was lower in dual-chamber minimal ventricular pacing than in conventional dual-chamber pacing (9.1% vs. 99.0%, P<0.001), whereas the percentage of atrial beats that were paced was similar in the two groups (71.4% vs. 70.4%, P=0.96). Persistent atrial fibrillation developed in 110 patients, 68 (12.7%) in the group assigned to conventional dual-chamber pacing and 42 (7.9%) in the group assigned to dual-chamber minimal ventricular pacing. The hazard ratio for development of persistent atrial fibrillation in patients with dual-chamber minimal ventricular pacing as compared with those with conventional dual-chamber pacing was 0.60 (95% confidence interval, 0.41 to 0.88; P=0.009), indicating a 40% reduction in relative risk. The absolute reduction in risk was 4.8%. The mortality rate was similar in the two groups (4.9% in the group receiving dual-chamber minimal ventricular pacing vs. 5.4% in the group receiving conventional dual-chamber pacing, P=0.54). CONCLUSIONS: Dual-chamber minimal ventricular pacing, as compared with conventional dual-chamber pacing, prevents ventricular desynchronization and moderately reduces the risk of persistent atrial fibrillation in patients with sinus-node disease. (ClinicalTrials.gov number, NCT00284830 [ClinicalTrials.gov].).

PURPOSE: An estimated 10% of breast and ovarian cancers result from hereditary causes. Current testing guidelines for germ line susceptibility genes in patients with breast carcinoma were developed to identify carriers of BRCA1/ 2 variants and have evolved in the panel-testing era. We evaluated the capability of the National Comprehensive Cancer Network (NCCN) guidelines to identify patients with breast cancer with pathogenic variants in expanded panel testing. METHODS: An institutional review board-approved multicenter prospective registry was initiated with 20 community and academic sites experienced in cancer genetic testing and counseling. Eligibility criteria included patients with a previously or newly diagnosed breast cancer who had not undergone either single- or multigene testing. Consecutive patients 18 to 90 years of age were consented and underwent an 80-gene panel test. Health Insurance Portability and Accountability Act-compliant electronic case report forms collected information on patient demographics, diagnoses, phenotypes, and test results. RESULTS: More than 1,000 patients were enrolled, and data records for 959 patients were analyzed; 49.95% met NCCN criteria, and 50.05% did not. Overall, 8.65% of patients had a pathogenic/likely pathogenic (P/LP) variant. Of patients who met NCCN guidelines with test results, 9.39% had a P/LP variant. Of patients who did not meet guidelines, 7.9% had a P/LP variant. The difference in positive results between these groups was not statistically significant (Fisher's exact test P = .4241). CONCLUSION: Our results indicate that nearly half of patients with breast cancer with a P/LP variant with clinically actionable and/or management guidelines in development are missed by current testing guidelines. We recommend that all patients with a diagnosis of breast cancer undergo expanded panel testing.

NIH Conferences17 June 2008National Institutes of Health Consensus Development Conference Statement: Hydroxyurea Treatment for Sickle Cell DiseaseFREEOtis W. Brawley, MD, Llewellyn J. Cornelius, PhD, LCSW, Linda R. Edwards, MD, Vanessa Northington Gamble, MD, PhD, Bettye L. Green, RN, Charles Inturrisi, PhD, Andra H. James, MD, MPH, Danielle Laraque, MD, Magda Mendez, MD, Carolyn J. Montoya, RN, MSN, CPNP, Brad H. Pollock, MPH, PhD, Lawrence Robinson, MD, MPH, Aaron P. Scholnik, MD, and Melissa Schori, MD, MBA*Otis W. Brawley, MDFrom Emory University and the American Cancer Society, Atlanta, Georgia; University of Maryland School of Social Work, Baltimore, Maryland; College of Medicine, University of Florida, Jacksonville, Jacksonville, Florida; The George Washington University, Washington, DC; Saint Joseph Regional Medical Center and African-American Women in Touch, South Bend, Indiana; Weill Medical College of Cornell University and Mount Sinai School of Medicine, New York, and Lincoln Medical and Mental Health Center, Bronx, New York; Women's Hemostasis and Thrombosis Clinic and Duke University Medical Center, Durham, North Carolina; National Association of Pediatric Nurse Practitioners and College of Nursing, University of New Mexico, Albuquerque, New Mexico; School of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, Texas; Philadelphia Department of Public Health, Philadelphia, Pennsylvania; Upper Peninsula Hematology/Oncology Associates and Cancer Research Office, Marquette General Health System, Marquette, Michigan; and Princeton Healthcare System, Princeton, New Jersey.Search for more papers by this author, Llewellyn J. Cornelius, PhD, LCSWFrom Emory University and the American Cancer Society, Atlanta, Georgia; University of Maryland School of Social Work, Baltimore, Maryland; College of Medicine, University of Florida, Jacksonville, Jacksonville, Florida; The George Washington University, Washington, DC; Saint Joseph Regional Medical Center and African-American Women in Touch, South Bend, Indiana; Weill Medical College of Cornell University and Mount Sinai School of Medicine, New York, and Lincoln Medical and Mental Health Center, Bronx, New York; Women's Hemostasis and Thrombosis Clinic and Duke University Medical Center, Durham, North Carolina; National Association of Pediatric Nurse Practitioners and College of Nursing, University of New Mexico, Albuquerque, New Mexico; School of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, Texas; Philadelphia Department of Public Health, Philadelphia, Pennsylvania; Upper Peninsula Hematology/Oncology Associates and Cancer Research Office, Marquette General Health System, Marquette, Michigan; and Princeton Healthcare System, Princeton, New Jersey.Search for more papers by this author, Linda R. Edwards, MDFrom Emory University and the American Cancer Society, Atlanta, Georgia; University of Maryland School of Social Work, Baltimore, Maryland; College of Medicine, University of Florida, Jacksonville, Jacksonville, Florida; The George Washington University, Washington, DC; Saint Joseph Regional Medical Center and African-American Women in Touch, South Bend, Indiana; Weill Medical College of Cornell University and Mount Sinai School of Medicine, New York, and Lincoln Medical and Mental Health Center, Bronx, New York; Women's Hemostasis and Thrombosis Clinic and Duke University Medical Center, Durham, North Carolina; National Association of Pediatric Nurse Practitioners and College of Nursing, University of New Mexico, Albuquerque, New Mexico; School of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, Texas; Philadelphia Department of Public Health, Philadelphia, Pennsylvania; Upper Peninsula Hematology/Oncology Associates and Cancer Research Office, Marquette General Health System, Marquette, Michigan; and Princeton Healthcare System, Princeton, New Jersey.Search for more papers by this author, Vanessa Northington Gamble, MD, PhDFrom Emory University and the American Cancer Society, Atlanta, Georgia; University of Maryland School of Social Work, Baltimore, Maryland; College of Medicine, University of Florida, Jacksonville, Jacksonville, Florida; The George Washington University, Washington, DC; Saint Joseph Regional Medical Center and African-American Women in Touch, South Bend, Indiana; Weill Medical College of Cornell University and Mount Sinai School of Medicine, New York, and Lincoln Medical and Mental Health Center, Bronx, New York; Women's Hemostasis and Thrombosis Clinic and Duke University Medical Center, Durham, North Carolina; National Association of Pediatric Nurse Practitioners and College of Nursing, University of New Mexico, Albuquerque, New Mexico; School of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, Texas; Philadelphia Department of Public Health, Philadelphia, Pennsylvania; Upper Peninsula Hematology/Oncology Associates and Cancer Research Office, Marquette General Health System, Marquette, Michigan; and Princeton Healthcare System, Princeton, New Jersey.Search for more papers by this author, Bettye L. Green, RNFrom Emory University and the American Cancer Society, Atlanta, Georgia; University of Maryland School of Social Work, Baltimore, Maryland; College of Medicine, University of Florida, Jacksonville, Jacksonville, Florida; The George Washington University, Washington, DC; Saint Joseph Regional Medical Center and African-American Women in Touch, South Bend, Indiana; Weill Medical College of Cornell University and Mount Sinai School of Medicine, New York, and Lincoln Medical and Mental Health Center, Bronx, New York; Women's Hemostasis and Thrombosis Clinic and Duke University Medical Center, Durham, North Carolina; National Association of Pediatric Nurse Practitioners and College of Nursing, University of New Mexico, Albuquerque, New Mexico; School of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, Texas; Philadelphia Department of Public Health, Philadelphia, Pennsylvania; Upper Peninsula Hematology/Oncology Associates and Cancer Research Office, Marquette General Health System, Marquette, Michigan; and Princeton Healthcare System, Princeton, New Jersey.Search for more papers by this author, Charles Inturrisi, PhDFrom Emory University and the American Cancer Society, Atlanta, Georgia; University of Maryland School of Social Work, Baltimore, Maryland; College of Medicine, University of Florida, Jacksonville, Jacksonville, Florida; The George Washington University, Washington, DC; Saint Joseph Regional Medical Center and African-American Women in Touch, South Bend, Indiana; Weill Medical College of Cornell University and Mount Sinai School of Medicine, New York, and Lincoln Medical and Mental Health Center, Bronx, New York; Women's Hemostasis and Thrombosis Clinic and Duke University Medical Center, Durham, North Carolina; National Association of Pediatric Nurse Practitioners and College of Nursing, University of New Mexico, Albuquerque, New Mexico; School of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, Texas; Philadelphia Department of Public Health, Philadelphia, Pennsylvania; Upper Peninsula Hematology/Oncology Associates and Cancer Research Office, Marquette General Health System, Marquette, Michigan; and Princeton Healthcare System, Princeton, New Jersey.Search for more papers by this author, Andra H. James, MD, MPHFrom Emory University and the American Cancer Society, Atlanta, Georgia; University of Maryland School of Social Work, Baltimore, Maryland; College of Medicine, University of Florida, Jacksonville, Jacksonville, Florida; The George Washington University, Washington, DC; Saint Joseph Regional Medical Center and African-American Women in Touch, South Bend, Indiana; Weill Medical College of Cornell University and Mount Sinai School of Medicine, New York, and Lincoln Medical and Mental Health Center, Bronx, New York; Women's Hemostasis and Thrombosis Clinic and Duke University Medical Center, Durham, North Carolina; National Association of Pediatric Nurse Practitioners and College of Nursing, University of New Mexico, Albuquerque, New Mexico; School of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, Texas; Philadelphia Department of Public Health, Philadelphia, Pennsylvania; Upper Peninsula Hematology/Oncology Associates and Cancer Research Office, Marquette General Health System, Marquette, Michigan; and Princeton Healthcare System, Princeton, New Jersey.Search for more papers by this author, Danielle Laraque, MDFrom Emory University and the American Cancer Society, Atlanta, Georgia; University of Maryland School of Social Work, Baltimore, Maryland; College of Medicine, University of Florida, Jacksonville, Jacksonville, Florida; The George Washington University, Washington, DC; Saint Joseph Regional Medical Center and African-American Women in Touch, South Bend, Indiana; Weill Medical College of Cornell University and Mount Sinai School of Medicine, New York, and Lincoln Medical and Mental Health Center, Bronx, New York; Women's Hemostasis and Thrombosis Clinic and Duke University Medical Center, Durham, North Carolina; National Association of Pediatric Nurse Practitioners and College of Nursing, University of New Mexico, Albuquerque, New Mexico; School of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, Texas; Philadelphia Department of Public Health, Philadelphia, Pennsylvania; Upper Peninsula Hematology/Oncology Associates and Cancer Research Office, Marquette General Health System, Marquette, Michigan; and Princeton Healthcare System, Princeton, New Jersey.Search for more papers by this author, Magda Mendez, MDFrom Emory University and the American Cancer Society, Atlanta, Georgia; University of Maryland School of Social Work, Baltimore, Maryland; College of Medicine, University of Florida, Jacksonville, Jacksonville, Florida; The George Washington University, Washington, DC; Saint Joseph Regional Medical Center and African-American Women in Touch, South Bend, Indiana; Weill Medical College of Cornell University and Mount Sinai School of Medicine, New York, and Lincoln Medical and Mental Health Center, Bronx, New York; Women's Hemostasis and Thrombosis Clinic and Duke University Medical Center, Durham, North Carolina; National Association of Pediatric Nurse Practitioners and College of Nursing, University of New Mexico, Albuquerque, New Mexico; School of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, Texas; Philadelphia Department of Public Health, Philadelphia, Pennsylvania; Upper Peninsula Hematology/Oncology Associates and Cancer Research Office, Marquette General Health System, Marquette, Michigan; and Princeton Healthcare System, Princeton, New Jersey.Search for more papers by this author, Carolyn J. Montoya, RN, MSN, CPNPFrom Emory University and the American Cancer Society, Atlanta, Georgia; University of Maryland School of Social Work, Baltimore, Maryland; College of Medicine, University of Florida, Jacksonville, Jacksonville, Florida; The George Washington University, Washington, DC; Saint Joseph Regional Medical Center and African-American Women in Touch, South Bend, Indiana; Weill Medical College of Cornell University and Mount Sinai School of Medicine, New York, and Lincoln Medical and Mental Health Center, Bronx, New York; Women's Hemostasis and Thrombosis Clinic and Duke University Medical Center, Durham, North Carolina; National Association of Pediatric Nurse Practitioners and College of Nursing, University of New Mexico, Albuquerque, New Mexico; School of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, Texas; Philadelphia Department of Public Health, Philadelphia, Pennsylvania; Upper Peninsula Hematology/Oncology Associates and Cancer Research Office, Marquette General Health System, Marquette, Michigan; and Princeton Healthcare System, Princeton, New Jersey.Search for more papers by this author, Brad H. Pollock, MPH, PhDFrom Emory University and the American Cancer Society, Atlanta, Georgia; University of Maryland School of Social Work, Baltimore, Maryland; College of Medicine, University of Florida, Jacksonville, Jacksonville, Florida; The George Washington University, Washington, DC; Saint Joseph Regional Medical Center and African-American Women in Touch, South Bend, Indiana; Weill Medical College of Cornell University and Mount Sinai School of Medicine, New York, and Lincoln Medical and Mental Health Center, Bronx, New York; Women's Hemostasis and Thrombosis Clinic and Duke University Medical Center, Durham, North Carolina; National Association of Pediatric Nurse Practitioners and College of Nursing, University of New Mexico, Albuquerque, New Mexico; School of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, Texas; Philadelphia Department of Public Health, Philadelphia, Pennsylvania; Upper Peninsula Hematology/Oncology Associates and Cancer Research Office, Marquette General Health System, Marquette, Michigan; and Princeton Healthcare System, Princeton, New Jersey.Search for more papers by this author, Lawrence Robinson, MD, MPHFrom Emory University and the American Cancer Society, Atlanta, Georgia; University of Maryland School of Social Work, Baltimore, Maryland; College of Medicine, University of Florida, Jacksonville, Jacksonville, Florida; The George Washington University, Washington, DC; Saint Joseph Regional Medical Center and African-American Women in Touch, South Bend, Indiana; Weill Medical College of Cornell University and Mount Sinai School of Medicine, New York, and Lincoln Medical and Mental Health Center, Bronx, New York; Women's Hemostasis and Thrombosis Clinic and Duke University Medical Center, Durham, North Carolina; National Association of Pediatric Nurse Practitioners and College of Nursing, University of New Mexico, Albuquerque, New Mexico; School of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, Texas; Philadelphia Department of Public Health, Philadelphia, Pennsylvania; Upper Peninsula Hematology/Oncology Associates and Cancer Research Office, Marquette General Health System, Marquette, Michigan; and Princeton Healthcare System, Princeton, New Jersey.Search for more papers by this author, Aaron P. Scholnik, MDFrom Emory University and the American Cancer Society, Atlanta, Georgia; University of Maryland School of Social Work, Baltimore, Maryland; College of Medicine, University of Florida, Jacksonville, Jacksonville, Florida; The George Washington University, Washington, DC; Saint Joseph Regional Medical Center and African-American Women in Touch, South Bend, Indiana; Weill Medical College of Cornell University and Mount Sinai School of Medicine, New York, and Lincoln Medical and Mental Health Center, Bronx, New York; Women's Hemostasis and Thrombosis Clinic and Duke University Medical Center, Durham, North Carolina; National Association of Pediatric Nurse Practitioners and College of Nursing, University of New Mexico, Albuquerque, New Mexico; School of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, Texas; Philadelphia Department of Public Health, Philadelphia, Pennsylvania; Upper Peninsula Hematology/Oncology Associates and Cancer Research Office, Marquette General Health System, Marquette, Michigan; and Princeton Healthcare System, Princeton, New Jersey.Search for more papers by this author, and Melissa Schori, MD, MBA*From Emory University and the American Cancer Society, Atlanta, Georgia; University of Maryland School of Social Work, Baltimore, Maryland; College of Medicine, University of Florida, Jacksonville, Jacksonville, Florida; The George Washington University, Washington, DC; Saint Joseph Regional Medical Center and African-American Women in Touch, South Bend, Indiana; Weill Medical College of Cornell University and Mount Sinai School of Medicine, New York, and Lincoln Medical and Mental Health Center, Bronx, New York; Women's Hemostasis and Thrombosis Clinic and Duke University Medical Center, Durham, North Carolina; National Association of Pediatric Nurse Practitioners and College of Nursing, University of New Mexico, Albuquerque, New Mexico; School of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, Texas; Philadelphia Department of Public Health, Philadelphia, Pennsylvania; Upper Peninsula Hematology/Oncology Associates and Cancer Research Office, Marquette General Health System, Marquette, Michigan; and Princeton Healthcare System, Princeton, New Jersey.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-148-12-200806170-00220 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail National Institutes of Health consensus and state-of-the- science statements are prepared by independent panels of health professionals and public representatives on the basis of 1) the results of a systematic literature review prepared under contract with the Agency for Healthcare Research and Quality (AHRQ), 2) presentations by investigators working in areas relevant to the conference questions during a 2-day public session, 3) questions and statements from conference attendees during open discussion periods that are part of the public session, and 4) closed deliberations by the panel during the remainder of the second day and morning of the third. This statement is an independent report of the panel and is not a policy statement of the National Institutes of Health or the U.S. government. The statement reflects the panel's assessment of medical knowledge available at the time the statement was written. Thus, it provides a “snapshot in time” of the state of knowledge on the conference topic. When reading the statement, keep in mind that new knowledge is inevitably accumulating through medical research.Sickle cell disease is an inherited blood disorder that affects 50 000 to 100 000 people in the United States. It is estimated that 2000 babies are born with sickle cell disease in the United States each year. Sickle cell disease was the first disease for which a specific molecular defect in a gene was identified, and it is the most common genetic disease identified as part of the Newborn Screening Program in the United States. The condition is chronic and lifelong, and it is associated with a decreased lifespan. Sickle cell disease is most common in people whose families come from Africa, South or Central America, Caribbean islands, Mediterranean countries (such as Turkey, Greece, and Italy), India, and Saudi Arabia.Sickle cell disease occurs when an infant inherits the gene for sickle hemoglobin from both parents (Hb SS, or sickle cell anemia) or the gene for sickle hemoglobin from 1 parent and another abnormal hemoglobin gene from the other parent. In addition, approximately 2 million Americans have the sickle cell trait (in which an infant inherits the gene for sickle hemoglobin from 1 parent and a normal hemoglobin gene from the other parent). Several additional sickle syndromes result from genotypes that include, but are not limited to, SCD-Sβ0, SCD-SC, SCD-SD, SCD-Sβ+, and SCD-SOarab.Erythrocytes (red blood cells) in people with sickle cell disease become deoxygenated (depleted of oxygen), dehydrated, and crescent-shaped or “sickled.” The cells aggregate, or clump together, and stick to blood vessel walls. Aggregation blocks blood flow within limbs and organs. This can cause painful episodes and permanent damage to the eyes, brain, heart, lungs, kidneys, liver, bones, and spleen. Infections and lung disease are the leading causes of death in people with sickle cell disease.Patients with sickle cell disease are frequently seen in emergency departments and hospitalized for pain crises. Standard treatments for acute pain crises include painkilling medications, hydration, and oxygen.Hydroxyurea was initially synthesized in Germany in 1869. Nearly 50 years ago, it was developed as an anticancer drug and has been used to treat myeloproliferative syndromes, some types of leukemia, melanoma, and ovarian cancer. It has also been used to treat psoriasis. Hydroxyurea was first tested in sickle cell disease in 1984. Initial studies show that it acts to increase the production of fetal hemoglobin–containing erythrocytes and dilute the number of sickled cells in circulation.In the mid-1990s, investigators of a major study randomly assigned nearly 300 adults with sickle cell disease who had more than 3 severe painful crises or episodes per year to hydroxyurea or placebo. (In the past, the term pain crises has been used; currently, the term severe pain episodes is preferred.) This study was stopped early because it clearly showed that hydroxyurea reduced the number and severity of pain episodes in patients with sickle cell disease compared with placebo. Follow-up with the trial participants, including patients who were originally given placebo and were later prescribed hydroxyurea after the drug was determined to be beneficial, has shown that hydroxyurea reduces the damaging effects of sickle cell disease and improves some aspects of quality of life. The drug also may extend survival. In 1998, the U.S. Food and Drug Administration approved hydroxyurea for prevention of pain crises in adults with sickle cell anemia. Although the efficacy of hydroxyurea has been established in adults, the evidence of its efficacy in children is not as strong; however, the emerging data are supportive.Although hydroxyurea is beneficial to some patients with sickle cell disease, several issues about use of the drug are unresolved. These include patient and health practitioner concerns about the overall safety and effectiveness of hydroxyurea, as well as a lack of providers expert in the treatment of patients with sickle cell disease.To more closely examine this important topic, the National Heart, Lung, and Blood Institute and the Office of Medical Applications of Research of the National Institutes of Health convened a Consensus Development Conference from 25 to 27 February 2008 to assess the available scientific evidence related to the following questions: 1) What is the efficacy (results from clinical studies) of hydroxyurea treatment for patients who have sickle cell disease in 3 groups: infants, preadolescents, and adolescents and adults? 2) What is the effectiveness (in everyday practice) of hydroxyurea treatment for patients who have sickle cell disease? 3) What are the short- and long-term harms of hydroxyurea treatment? 4) What are the barriers to hydroxyurea treatment for patients who have sickle cell disease, and what are the potential solutions? 5) What are the future research needs?At the conference, invited speakers presented information pertinent to these questions, and a systematic literature review prepared under contract with the AHRQ (www.ahrq.gov/clinic/tp/hydscdtp.htm) was summarized. Conference attendees provided both oral and written statements in response to the key questions. The panel members weighed all of this evidence as they addressed the conference questions.This consensus statement is intended to provide researchers, health care providers, patients, and other interested members of the general public with an objective assessment of what is known about hydroxyurea as a treatment for sickle cell disease, and what questions remain.1. What Is the Efficacy (Results from Clinical Studies) of Hydroxyurea Treatment for Patients Who Have Sickle Cell Disease in 3 Groups: Infants, Preadolescents, and Adolescents and Adults?Efficacy is the therapeutic effect of an intervention in a controlled setting, in contrast to effectiveness, which is the therapeutic effect of an intervention in real-world situations. The spectrum of sickle cell disease includes the SCD-SS, SCD-Sβ0, SCD-SC, SCD-SD, SCD-Sβ+, and SCD-SOarab genotypes. Efficacy studies have varied in their inclusion of specific genotypes, but almost all include SCD-SS. In addition, the geographic origin of sickle cell disease is associated with different haplotypes and varying degrees of clinical severity. The 3 most common and phenotypically distinct haplotypes are Senegalese, Benin, and Bantu. Other geographic areas of origin associated with sickle cell disease include Saudi Arabia and the Indian subcontinent. The Benin and Bantu haplotypes are more common among people residing in the Western Hemisphere and are associated with worse clinical outcomes. Response to hydroxyurea therapy may vary by haplotype or genotype. However, few studies of efficacy have appropriately accounted for the heterogeneity of study populations that differed by genotype and phenotype as well as by demographic factors (such as sex and age).Although clinical experience on the use of hydroxyurea for treating sickle cell disease has been amassed over nearly 25 years, the strength of evidence supporting the efficacious use of hydroxyurea is not equivalent across age groups. Hydroxyurea is currently U.S. Food and Drug Administration–approved for use in adults and is the only treatment for sickle cell disease that modifies the disease process. Evidence is strong in adults but more limited in children because the sole randomized clinical trial in the latter population had a weak study design, small sample, and short follow-up. Nonetheless, the evidence in children does not contradict the findings in adults that hydroxyurea improves hematologic variables and decreases hospitalization rates. Published evidence based on weaker, observational study designs, such as cohort studies, before-and-after studies, case series, and case reports, suggests that hydroxyurea is efficacious. Adding to the difficulty in reaching a consensus on the use of hydroxyurea is that published efficacy studies are difficult to interpret because diverse outcome measures have been used, including hematologic end points; reduced incidence of severe pain episodes, the acute chest syndrome, hospitalizations, strokes, and kidney and spleen damage; and need for transfusion therapy. Studies currently under way should provide more information regarding the benefit of hydroxyurea in preventing organ damage and additional sickle cell disease outcomes. Elucidating the mechanism of action of hydroxyurea should prove useful in developing new agents.Adolescents and AdultsStrong evidence supports the efficacy of hydroxyurea use in adults. The published clinical trials included adolescents; however, they were not analyzed or reported as a separate group. Outcomes were diverse and included blood markers as measures of treatment effect (for example, hemoglobin level, hemoglobin F cell count, percentage of hemoglobin F, mean corpuscular volume, leukocyte count, and platelet count). Studies used a variety of clinical outcome measures (severe pain episodes, hospitalizations, the acute chest syndrome, blood transfusion therapy, mortality, priapism [unwanted, prolonged, painful erection], strokes, and leg ulcers) and examined the effects of hydroxyurea on the spleen, kidneys, and blood flow to the brain (Table 1).Table 1. Study Outcomes for Adults Receiving Hydroxyurea for Sickle Cell DiseaseAlthough a reduction in mortality with hydroxyurea therapy has been reported, the published trial was not specifically designed to assess this end point. It is therefore difficult to draw definitive conclusions about the effect of hydroxyurea on mortality.PreadolescentsThe evidence varies on whether the use of hydroxyurea improves short-term end points, especially hematologic measures, in preadolescent populations beyond infancy (Table 2).Table 2. Study Outcomes for Preadolescent Children beyond Infancy Receiving Hydroxyurea for Sickle Cell DiseaseEvidence is strong for an improvement in blood markers and reduced hospitalizations and moderate for a reduction in the incidence of pain crises. Ongoing investigations in this age group will determine the efficacy of hydroxyurea treatment for children with SCD-SS, a history of stroke, and too much iron (iron overload).InfantsNo published, well-designed clinical trials have evaluated the efficacy of hydroxyurea treatment for infants. Ongoing prospective trials and observational studies are attempting to address this gap. The end points of these studies include prevention of damage to the kidney and spleen and improvements in blood markers that predict long-term clinical outcomes.In summary, the efficacy of hydroxyurea treatment for adults with SCD-SS is established. Although the evidence for efficacy of hydroxyurea treatment for children is not as strong, the emerging data are supportive. Future directions include evaluation of efficacy in preadolescent children and infants and further development of other therapeutic techniques, including stem-cell transplantation and gene therapy. Stem-cell transplantation can cure sickle cell anemia.2. What Is the Effectiveness (in Everyday Practice) of Hydroxyurea Treatment for Patients Who Have Sickle Cell Disease?Effectiveness is the therapeutic effect of an intervention as demonstrated or observed in patients in their usual care setting. The efficacy of hydroxyurea in treating adults with sickle ce

CONTEXT: Hypercalcemia of malignancy (HCM) in patients with advanced cancer is often caused by excessive osteoclast-mediated bone resorption. Patients may not respond to or may relapse after iv bisphosphonate therapy. OBJECTIVE: We investigated whether denosumab, a potent inhibitor of osteoclast-mediated bone resorption, reduces serum calcium in patients with bisphosphonate-refractory HCM. DESIGN, SETTING, AND PARTICIPANTS: In this single-arm international study, participants had serum calcium levels corrected for albumin (CSC) >12.5 mg/dL (3.1 mmol/L) despite bisphosphonates given >7 and ≤30 days before screening. INTERVENTION: Patients received 120 mg sc denosumab on days 1, 8, 15, and 29 and then every 4 weeks. MAIN OUTCOME MEASURES: The primary endpoint was the proportion of patients with CSC ≤11.5 mg/dL (2.9 mmol/L) (response) by day 10. Secondary endpoints included response by visit, duration of response, and the proportion of patients with a complete response (CSC ≤10.8 mg/dL [2.7 mmol/L]) by day 10 and during the study. RESULTS: Patients (N = 33) had solid tumors or hematologic malignancies. By day 10, 21 patients (64%) reached CSC ≤11.5 mg/dL, and 12 patients (33%) reached CSC ≤10.8 mg/dL. During the study, 23 patients (70%) reached CSC ≤11.5 mg/dL, and 21 patients (64%) reached CSC ≤10.8 mg/dL. Estimated median response duration was 104 days. The most common serious adverse events were hypercalcemia worsening (5 patients, 15%) and dyspnea (3 patients, 9%). CONCLUSIONS: In patients with HCM despite recent iv bisphosphonate treatment, denosumab lowered serum calcium in 64% of patients within 10 days, inducing durable responses. Denosumab may offer a new treatment option for HCM.

Aerobic and resistance exercise training is a cornerstone of early outpatient cardiac rehabilitation (CR) and provides impressive benefits for patients. The components of the exercise prescription for patients with cardiovascular diseases are provided in guideline documents from several professional organizations and include frequency (how many sessions per week); intensity (how hard to exercise); time (duration of the exercise training session); type (modalities of exercise training); volume (the total amount or dose of exercise); and progression (the rate of increasing the dose of exercise). The least discussed, least appreciated, and most challenging component of the exercise prescription for CR health care professionals is the rate of progression of the dose of exercise. One reason for this observation is the heterogeneity of patients who participate in CR. All components of the exercise prescription should be developed specifically for each individual patient. This statement provides an overview of the principles of exercise prescription for patients in CR with special emphasis on the rate of progression. General recommendations for progression are given and patient case examples are provided to illustrate the principles of progression in exercise training.

Human Parvovirus B19 (PV B19) is one of the several recently described 'emerging viruses' and has been identified as the etiological agent of 'fifth disease' in childhood. Human PV B19, which is the etiological agent of transient erythroblastopenia in hemolytic anemia, is also a recognized rare cause of red cell aplasia in immunocompromised patients, including transplant recipients. To date, 26 cases of PV B19-induced red cell aplasia have been reported in solid organ transplant recipients. Twelve patients had cyclosporine-based immunosuppression and 14 had tacrolimus-based immunosuppression. Sixteen of these patients required treatment with commercial intravenous immunoglobulin alone, 1 required treatment with intravenous immunoglobulin and plasmapheresis, 4 required intravenous immunoglobulin and erythropoietin, 1 required treatment with intravenous immunoglobulin and conversion of tacrolimus to cyclosporine, 1 had improvement in hematocrit with erythropoietin alone and in 3 patients the disease was self-limiting. Herein, we report a case of pure red cell aplasia caused by acute PV B19 infection in a renal transplant recipient in whom the immunosuppressive regimen included prednisone, mycophenolate mofetil and tacrolimus and the red cell aplasia resolved with discontinuation of mycophenolate mofetil.

BACKGROUND: Propofol is a commonly used anesthetic induction agent in pediatric anesthesia that, until recently, was used with caution as an intravenous infusion agent for sedation in pediatric intensive care. Few data have described propofol kinetics in critically ill children. METHODS: Twenty-one critically ill ventilated children aged 1 week to 12 yr were sedated with 4-6 mg. kg(-1).h(-1) of 2% propofol for up to 28 h, combined with a constant morphine infusion. Whole blood concentration of propofol was measured at steady state and for 24 h after infusion using high-performance liquid chromatography. RESULTS: A propofol infusion rate of 4 mg. kg(-1).h(-1) achieved adequate sedation scores in 17 of 20 patients. In 2 patients the dose was reduced because of hypotension, and 1 patient was withdrawn from the study because of a increasing metabolic acidosis. Mixed-effects population models were fitted to the blood propofol concentration data. The pharmacokinetics were best described by a three-compartment model. Weight was a significant covariate for all structural model parameters; Cl, Q2, Q3, V1, and V2 were proportional to weight. Estimates for these parameters were 30.2, 16.0, and 13.3 ml. kg(-1).min(-1) and 0.584 and 1.36 l/kg, respectively. The volume of the remaining peripheral compartment, V3, had a constant component (103 l) plus an additional weight-related component (5.67 l/kg). Values for Cl were reduced (typically by 26%) in children who had undergone cardiac surgery. CONCLUSIONS: Propofol kinetics are altered in very small babies and in children recovering from cardiac surgery. Increased peripheral distribution volume and reduced metabolic clearance following surgery causes prolonged elimination.

Belantamab mafodotin (belamaf), an antibody-drug conjugate approved for the treatment of relapsed and refractory multiple myeloma (RRMM), is an anti B-cell maturation antigen (BCMA) agent. DREAMM-1, a first in-human trial of belamaf, reported several ocular toxicities requiring dose adjustments, dose delays and treatment discontinuations. In DREAMM-1, 53% of patients in part-1 and 63% of patients in part-2 had ocular toxicity. Similarly, 73% of patients in DREAMM-2 had keratopathy (71% in 2.5 mg/kg versus 75% in 3.4 mg/kg) with the most common symptoms being blurred vision and dry eyes. Ocular toxicity of belamaf is attributed to microtubule-disrupting monomethylauristatin-F (MMAF), a cytotoxic payload of the drug that causes an off-target damage to the corneal epithelial cells. Ocular adverse events (AEs) of belamaf are more frequent at higher doses compared with lower doses. Higher belamaf dose, history of dry eyes and soluble BCMA are associated with increased risk of corneal toxicity. Absence of ocular symptoms does not exclude the possibility of belamaf-induced ocular toxicity, so patients need slit lamp and Snellen visual acuity testing to detect microcytic-like epithelial changes and visual decline. Corticosteroid eyes drops for 4-7 days prior to belamaf dose do not prevent ocular AEs and may cause steroid-related AEs instead. Keratopathy and Visual Acuity scale ( KVA ) is recommended to document the severity of belamaf-induced ocular toxicity and make treatment adjustments. Management of toxicity includes dosage modifications, treatment interruption or discontinuations and preservative-free artificial tears along with close ophthalmology and hematology-oncology follow-ups.

Articular cartilage lesions in the athletic population are observed with increasing frequency and, due to limited intrinsic healing capacity, can lead to progressive pain and functional limitation over time. If left untreated, isolated cartilage lesions can lead to progressive chondropenia or global cartilage loss over time. A chondropenia curve is described to help predict the outcome of cartilage injury based on different lesion and patient characteristics. Nutriceuticals and chondroprotective agents are being investigated as tools to slow the development of chondropenia. Several operative techniques have been described for articular cartilage repair or replacement and, more recently, cartilage regeneration. Rehabilitation guidelines are being developed to meet the needs of these new techniques. Next-generation techniques are currently evaluated to optimize articular cartilage repair biology and to provide a repair cartilage tissue that can withstand the high mechanical loads experienced by the athlete with consistent long-term durability.

Multiple myeloma is a treatable, but currently incurable, hematological malignancy of plasma cells characterized by diverse and complex tumor genetics for which precision medicine approaches to treatment are lacking. The Multiple Myeloma Research Foundation’s Relating Clinical Outcomes in Multiple Myeloma to Personal Assessment of Genetic Profile study ( NCT01454297 ) is a longitudinal, observational clinical study of newly diagnosed patients with multiple myeloma (n = 1,143) where tumor samples are characterized using whole-genome sequencing, whole-exome sequencing and RNA sequencing at diagnosis and progression, and clinical data are collected every 3 months. Analyses of the baseline cohort identified genes that are the target of recurrent gain-of-function and loss-of-function events. Consensus clustering identified 8 and 12 unique copy number and expression subtypes of myeloma, respectively, identifying high-risk genetic subtypes and elucidating many of the molecular underpinnings of these unique biological groups. Analysis of serial samples showed that 25.5% of patients transition to a high-risk expression subtype at progression. We observed robust expression of immunotherapy targets in this subtype, suggesting a potential therapeutic option. Longitudinal genomic and transcriptomic profiling of 1,143 patients with multiple myeloma by the Relating Clinical Outcomes in Multiple Myeloma to Personal Assessment of Genetic Profile study yields an improved copy number and gene expression subtype scheme, most notably a high-risk proliferative subtype associated with complete loss of RB1 or MAX.

STUDY DESIGN: To report on the preliminary results of preparing and reconstructing the pars interarticularis with a cable-screw construct. The success of previous techniques to repair the pars defect has been variable. OBJECTIVES: To assess the results of a new technique for stabilizing the pars interarticularis, using the strongest materials, pedicle screws, and cables in the strongest bony elements--the pedicle and lamina. SUMMARY OF BACKGROUND DATA: Previous techniques have been inadequate structurally to stabilize the pars interarticularis effectively, or the techniques were difficult to perform. Placing a screw across the defect was technically difficult and took away from the surface area of the fusion. The Scott technique used wiring between the transverse process and spinous process; and in the Morscher Technique, a hook screw was used to repair the pars defect--a technically difficult procedure, using bulky hardware. METHODS: Patients with pars interarticularis defects were carefully selected for this technique if they had primarily low back pain that did not respond to conservative treatment. The eligible patient had Grade I or less spondylolisthesis, little or no desiccation detectable on magnetic resonance imaging, and pain reproduced with injection of the pars defect. Surgical technique involved placing a special pedicle cable-screw into the pedicle of the involved vertebra. A double cable was passed underneath the lamina, threaded through the hole of the pedicle screw, and wrapped around the spinous process. The cables were simultaneously tensioned and crimped. A tricortical bone graft was compressed between the pedicle and lamina. RESULTS: Seven patients had this technique with a follow-up of 25.5 months (range, 19-37 months). The mean age was 20.5 years (range, 12-32 years), and the mean duration of symptoms was 31 months. All patients had severe pain before surgery that prevented participation in sports and normal daily activities. After surgery, results in five were rated as excellent and in two as good, according to the Prolo score. There were no failures of the cable-screw constructs, and all of the defects appear to have united solidly. CONCLUSION: The cable-screw construct uses the strongest anchors (the pedicle and the lamina) and uses compression obtained with cables to stabilize the pars interarticularis. Early results indicate that this is a safe and effective technique for this difficult problem.

AIM: To describe the findings from a qualitative study exploring acute care nurses' experiences with patient falls. BACKGROUND: Patient falls continue to be a problem in acute care settings for nurses at the point of care. Despite the growing body of knowledge related to risk factors and interventions for fall prevention, minimal attention has been given to nurses' perspectives of patient falls. DESIGN: A qualitative descriptive design was used. METHOD: Focus group discussions were conducted with nurses working on a cross-section of inpatient acute care settings. Audio-taped sessions were transcribed and analysed thematically. RESULTS: Nurses described their experience of falls as 'knowing the patient as safe', an ongoing affirmation that the patient was free from harm. In this focused, narrowly defined and highly specific knowing, nurses employed the key strategies of assessment, monitoring and communicating. Variable conditions influenced whether these strategies were effective in giving nurses the knowledge they needed to keep the patient safe. When strategies failed to provide nurses with knowledge of their patients as safe and patients fell, this created considerable stress for nurses and prompted them to use a range of coping strategies. CONCLUSION: Knowing the patient as safe has the potential to resolve the tension between patient safety and independence. The critical, often taken for granted, activities used by nurses in this knowing must be expanded to include the meaning falls have for patients and attend to factors beyond nurses control such as environmental redesign and staffing. RELEVANCE TO CLINICAL PRACTICE: Nurses play an important role in fall prevention through knowing the patient as safe but must be supported through the use of a multi-faceted approach extending from the individual nurse to the institutional level.

The changes in people's life rhythm and improvement in material levels that happened in recent years increased the number of people suffering from high blood pressure in the world. Therefore, as a cardiac complication of hypertension, the prevalence of hypertensive heart disease has increased annually, it has seriously endangered the safety of human life, and the effective prediction of hypertensive heart disease has become a worldwide problem. This paper uses the newly proposed XGBSVM hybrid model to predict whether hypertensive patients will develop hypertensive heart disease within three years. The final experiment proves that through this model, hypertensive patients can learn their risk of hypertensive heart disease within 3 years and then undergo targeted preventive treatment, thereby reducing the psychological, physiological and economic burden. This paper confirms that the machine learning can be successfully applied in the biomedical field, with strong real-world significance and research value.

Hypercalcemia of malignancy (HCM), caused primarily by tumor-induced bone resorption, may lead to renal failure, coma, and death. Although HCM can be treated with intravenous bisphosphonates, patients may not respond or may relapse on therapy. Denosumab binds the bone resorption mediator RANKL. In this single-arm, open-label, proof-of-concept study, HCM patients with albumin-corrected serum calcium (CSC) levels greater than 12.5mg/dL (Common Terminology Criteria for Adverse Events grade ≥3) despite recent intravenous bisphosphonate treatment received subcutaneous denosumab on days 1, 8, 15, and 29, and then every 4 weeks. The primary endpoint was the proportion of patients with CSC 11.5mg/dL or less (grade ≤1) within 10 days of denosumab initiation. In a prespecified interim analysis, 15 patients received denosumab (median CSC = 13.6mg/dL). Time to response and response duration were analyzed with Kaplan–Meier methods. All statistical tests were two-sided. By day 10, 12 patients (80%; 95% exact confidence interval [CI] = 52% to 96%) responded (CSC ≤11.5mg/dL); median response duration was 26 days. Ten patients (67%; 95% exact CI = 38% to 88%) had complete responses (CSC ≤10.8mg/dL) by day 10. Denosumab may offer a new treatment option for HCM. Clinicaltrials.gov identifier: NCT00896454.

Background: The Sherlock 3CG™ Tip Confirmation System (TCS) provides real-time peripherally inserted central catheter (PICC) tip insertion information using passive magnetic navigation and patient cardiac electrical activity. It is an alternative tip confirmation method to fluoroscopy or chest X-ray for PICC tip insertion confirmation in adults. The purpose of this study was to evaluate time and cost of the Sherlock 3CG TCS and blind insertion with chest X-ray tip confirmation (BI/CXR) for PICC insertions. Methods: A cross-sectional, observational Time and Motion study was conducted. Data were collected at four hospitals in the US. Two hospitals used Sherlock 3CG TCS and two hospitals used BI/CXR to place/confirm successful PICC tip location. Researchers observed PICC insertions, collecting data from the beginning (ie, PICC kit opening) to catheter tip confirmation (ie, released for intravenous [IV] therapy). An economic model was developed to project outcomes for a larger population. Results: A total of 120 subjects were enrolled, with 60 subjects enrolled in each arm and 30 enrolled at each of the four US hospitals. The mean time from initiation of the PICC procedure to the time to release for IV therapy was 33.93 minutes in the Sherlock 3CG arm and 176.32 minutes in the BI/CXR arm ( p < 0.001). No malpositions were observed for PICC insertions using the Sherlock 3CG TCS, while 20% of subjects in the BI/CXR arm had a malposition. BI/CXR subjects had significantly more total malpositions (mean 0.23 vs. 0, p < 0.001). For a hypothetical population of 1,000 annual patients, adoption of Sherlock 3CG TCS was predicted to be cost saving compared with BI/CXR in all three analysis years. Conclusion: The results from this study demonstrate that Sherlock 3CG TCS, when compared with BI/CXR, is a superior alternative with regard to time to release subject to therapy, malposition rates, and minimization of X-ray exposure. Keywords: vascular access devices, catheters, catheterization, peripheral, X-ray therapy, cost analysis, Time and Motion studies

3,3'-Diindolylmethane (DIM) is a stable condensation product of indole-3-carbanol, a potential breast cancer chemoprevention agent. Human breast cancer cell lines were studied to better understand its mechanisms. In vitro experiments were done in MCF-7, T47D, BT-20 and BT-474 cells using MTT, ELISA, immunoblotting assays, reverse transcription-PCR, protein half-life, confocal microscopy, cell fractionation, and immunoprecipitation assays. We found that DIM inhibited the growth of all four breast cancer cell lines (IC(50)s, 25-56 micromol/L). Because BT-20 and BT-474 overexpressed Her-2 and activated Akt, and BT-20 lacks estrogen receptor, these were studied further. In both cell lines, DIM appeared to induce expression of p27(kip) protein before the loss of cell viability and apoptosis. In BT-20 cells, DIM also inhibited expression of activated Akt, but this appeared after p27(kip) induction. In both cell lines, DIM induced p27(kip) transcript expression within 6 h. DIM prolonged the p27(kip) protein half-life in BT-20 but not BT-474 cells. We also showed, for the first time, that DIM induced nuclear localization of p27(kip) in both cell lines. Moreover, in BT-20 cells, DIM induced a decrease in p27(kip) phosphorylation at Thr(187), and its association with the 14-3-3 protein, which helped to explain the protein half-life increase and nuclear localization, respectively. DIM modulates p27(kip) through transcription, prolongation of protein half-life, and nuclear localization. These effects appear to be independent of Her-2, Akt, or estrogen receptor status and should support further study for its chemoprevention potential in breast cancer.

OBJECTIVE: To identify a new angiographic parameter associated with poor short- and long-term outcomes with nitinol stenting in the larger infrainguinal arteries. BACKGROUND: Nitinol stents have proven to be useful and safe, but imperfect, tools for treating claudication and limb-threatening ischemia. Primary and secondary patency in superficial femoral artery (SFA) occlusions treated with nitinol stents are up to 80% at 1 year, but restenosis is between 40-50% at 2 years. The causes of SFA and popliteal restenosis remain unclear. Stent fracture has been implicated in some cases of restenosis, but this is clearly the minority. Chronic mechanical trauma to the arteries caused by native vessel-stent interaction, intensified by limb motion over time, appears to be a more plausible explanation. METHODS: Presented here are 2 cases of restenosis apparently caused by acute and chronic trauma to the native vessel from interaction of the artery with the ends of relatively rigid nitinol stent systems. RESULTS: The source of some future restenotic and occlusive events are not apparent using routine angiography techniques. CONCLUSION: The additional step of an on-table leg bend test at 80-90 degrees will allow the interventionalist to visualize many cases of negative interaction between the native artery and the stents that will occur during routine movement. This allows the operator to potentially avoid stent-induced arterial trauma.

The high cost of capital equipment, demands of the world markets, and continuity requirements of many technological processes have forced industry to operate three-shift, 24-hour days. Workers on fixed schedules experience no particular problems from shift work, but those who are shifted periodically can undergo physiological and emotional disturbances. These disturbances occur because most human systems function according to circadian rhythms that can be easily disoriented. The primary cause is the periodic shifting of the light-dark, wake-sleep cycles. Extensive literature exists on the cause and symptoms of disturbances in the human physiological rhythms. The information contained in this literature can be applied to protecting the health and well-being of the worker.

The US Food and Drug Administration (FDA) consider menthol an effective substance, which help in common cold symptoms and labeled to have low toxicity profile. Direct exposure to high menthol amount has been reported in animal; but no studies have been done to show the effect of menthol on long-term use in humans. Up to our knowledge we are reporting a rare case of chronic exposure to significant amount of menthol associated with cutaneous, gastrointestinal and neurological manifestations.