Mental Practice: Applying Successful Strategies in Sports to the Practice of Emergency Medicine.

Emergency physicians are expected to learn and maintain a large and varied set of competencies for clinical practice. These include high acuity, low occurrence procedures that may not be encountered frequently in the clinical environment and are difficult to practice with high fidelity and frequency in a simulated environment. Mental practice is a form of a cognitive walk-through that has been shown to be an effective method for improving motor and cognitive skills, with literature in sports science and emerging evidence supporting its use in medicine. In this article, we review the literature on mental practice in sports and medicine as well as the underlying neuroscientific theories that support its use. We review best-known practices and provide a framework to design and use mental imagery scripts to augment learning and maintaining the competencies necessary for physicians at all levels of training and clinical environments in the practice of emergency medicine.

Cost-impact analysis of baroreflex activation therapy in chronic heart failure patients in the United States.

BACKGROUND: The study evaluated the cost of baroreflex activation therapy plus guideline directed therapy (BAT + GDT) compared to GDT alone for HF patients with reduced ejection fraction and New York Heart Association Class III or II (with a recent history of III). Baroreflex activation therapy (BAT) is delivered by an implantable device that stimulates the baroreceptors through an electrode attached to the outside of the carotid artery, which rebalances the autonomic nervous system to regain cardiovascular (CV) homeostasis. The BeAT-HF trial evaluated the safety and effectiveness of BAT. METHODS: A cost impact model was developed from a U.S. health care payer or integrated delivery network perspective over a 3-year period for BAT + GDT versus GDT alone. Expected costs were calculated by utilizing 6-month data from the BeAT-HF trial and existing literature. HF hospitalization rates were extrapolated based on improvement in NT-proBNP. RESULTS: At baseline the expected cost of BAT + GDT were $29,526 per patient more than GDT alone due to BAT device and implantation costs. After 3 years, the predicted cost per patient was $9521 less expensive for BAT + GDT versus GDT alone due to lower rates of significant HF hospitalizations, CV non-HF hospitalizations, and resource intensive late-stage procedures (LVADs and heart transplants) among the BAT + GDT group. CONCLUSIONS: BAT + GDT treatment becomes less costly than GDT alone beginning between years 1 and 2 and becomes less costly cumulatively between years 2 and 3, potentially providing significant savings over time. As additional BeAT-HF trial data become available, the model can be updated to show longer term effects.

Medical, therapeutic, and recreational use of cannabis among young men who have sex with men living with HIV.

Cannabis plays a role in symptoms management in HIV, especially the alleviation of pain and nausea and stimulation of appetite, and prevalence of cannabis use in HIV-positive populations exceeds that of the general U.S. population. Previous research has described an "overlap" between medical and recreational cannabis use among persons living with HIV. To understand better the motives associated cannabis use among young men who have sex with men living with HIV (HIV+ YMSM), we conducted semi-structured interviews with 30 HIV+YMSM in Denver and Chicago. Interviews were audio-recorded, transcribed, and coded by a diverse team of analysts. In addition to findings that mapped onto previously identified medical motives and recreational motives, we identified several themes that straddled medical and recreational use in a domain we describe as therapeutic. Themes identified in this therapeutic domain of cannabis use include (a) enhanced introspection among individuals that promotes psychological adjustment to an HIV diagnosis, improved medical management, and future orientation; (b) reflection processes that mitigate interpersonal conflict and improve interpersonal communication; and (c) a social-therapeutic phenomena of cannabis use among young persons with living HIV that is characterized by both enhanced introspection and improved interpersonal communication. Our findings suggest a spectrum of cannabis use among HIV+ YMSM that may be characterized not only by an overlap between medical and recreational use, but also by a distinct therapeutic domain that incorporates stress alleviation and cognitive expansion processes to improve focus on HIV management and self-care.

Clinical Practice Guideline: Nosebleed (Epistaxis).

OBJECTIVE: Nosebleed, also known as epistaxis, is a common problem that occurs at some point in at least 60% of people in the United States. While the majority of nosebleeds are limited in severity and duration, about 6% of people who experience nosebleeds will seek medical attention. For the purposes of this guideline, we define the target patient with a nosebleed as a patient with bleeding from the nostril, nasal cavity, or nasopharynx that is sufficient to warrant medical advice or care. This includes bleeding that is severe, persistent, and/or recurrent, as well as bleeding that impacts a patient's quality of life. Interventions for nosebleeds range from self-treatment and home remedies to more intensive procedural interventions in medical offices, emergency departments, hospitals, and operating rooms. Epistaxis has been estimated to account for 0.5% of all emergency department visits and up to one-third of all otolaryngology-related emergency department encounters. Inpatient hospitalization for aggressive treatment of severe nosebleeds has been reported in 0.2% of patients with nosebleeds. PURPOSE: The primary purpose of this multidisciplinary guideline is to identify quality improvement opportunities in the management of nosebleeds and to create clear and actionable recommendations to implement these opportunities in clinical practice. Specific goals of this guideline are to promote best practices, reduce unjustified variations in care of patients with nosebleeds, improve health outcomes, and minimize the potential harms of nosebleeds or interventions to treat nosebleeds. The target patient for the guideline is any individual aged ≥3 years with a nosebleed or history of nosebleed who needs medical treatment or seeks medical advice. The target audience of this guideline is clinicians who evaluate and treat patients with nosebleed. This includes primary care providers such as family medicine physicians, internists, pediatricians, physician assistants, and nurse practitioners. It also includes specialists such as emergency medicine providers, otolaryngologists, interventional radiologists/neuroradiologists and neurointerventionalists, hematologists, and cardiologists. The setting for this guideline includes any site of evaluation and treatment for a patient with nosebleed, including ambulatory medical sites, the emergency department, the inpatient hospital, and even remote outpatient encounters with phone calls and telemedicine. Outcomes to be considered for patients with nosebleed include control of acute bleeding, prevention of recurrent episodes of nasal bleeding, complications of treatment modalities, and accuracy of diagnostic measures. This guideline addresses the diagnosis, treatment, and prevention of nosebleed. It focuses on nosebleeds that commonly present to clinicians via phone calls, office visits, and emergency room encounters. This guideline discusses first-line treatments such as nasal compression, application of vasoconstrictors, nasal packing, and nasal cautery. It also addresses more complex epistaxis management, which includes the use of endoscopic arterial ligation and interventional radiology procedures. Management options for 2 special groups of patients-patients with hereditary hemorrhagic telangiectasia syndrome and patients taking medications that inhibit coagulation and/or platelet function-are included in this guideline. This guideline is intended to focus on evidence-based quality improvement opportunities judged most important by the guideline development group. It is not intended to be a comprehensive, general guide for managing patients with nosebleed. In this context, the purpose is to define useful actions for clinicians, generalists, and specialists from a variety of disciplines to improve quality of care. Conversely, the statements in this guideline are not intended to limit or restrict care provided by clinicians based on their experience and assessment of individual patients. ACTION STATEMENTS: The guideline development group made recommendations for the following key action statements: (1) At the time of initial contact, the clinician should distinguish the nosebleed patient who requires prompt management from the patient who does not. (2) The clinician should treat active bleeding for patients in need of prompt management with firm sustained compression to the lower third of the nose, with or without the assistance of the patient or caregiver, for 5 minutes or longer. (3a) For patients in whom bleeding precludes identification of a bleeding site despite nasal compression, the clinician should treat ongoing active bleeding with nasal packing. (3b) The clinician should use resorbable packing for patients with a suspected bleeding disorder or for patients who are using anticoagulation or antiplatelet medications. (4) The clinician should educate the patient who undergoes nasal packing about the type of packing placed, timing of and plan for removal of packing (if not resorbable), postprocedure care, and any signs or symptoms that would warrant prompt reassessment. (5) The clinician should document factors that increase the frequency or severity of bleeding for any patient with a nosebleed, including personal or family history of bleeding disorders, use of anticoagulant or antiplatelet medications, or intranasal drug use. (6) The clinician should perform anterior rhinoscopy to identify a source of bleeding after removal of any blood clot (if present) for patients with nosebleeds. (7a) The clinician should perform, or should refer to a clinician who can perform, nasal endoscopy to identify the site of bleeding and guide further management in patients with recurrent nasal bleeding, despite prior treatment with packing or cautery, or with recurrent unilateral nasal bleeding. (8) The clinician should treat patients with an identified site of bleeding with an appropriate intervention, which may include one or more of the following: topical vasoconstrictors, nasal cautery, and moisturizing or lubricating agents. (9) When nasal cautery is chosen for treatment, the clinician should anesthetize the bleeding site and restrict application of cautery only to the active or suspected site(s) of bleeding. (10) The clinician should evaluate, or refer to a clinician who can evaluate, candidacy for surgical arterial ligation or endovascular embolization for patients with persistent or recurrent bleeding not controlled by packing or nasal cauterization. (11) In the absence of life-threatening bleeding, the clinician should initiate first-line treatments prior to transfusion, reversal of anticoagulation, or withdrawal of anticoagulation/antiplatelet medications for patients using these medications. (12) The clinician should assess, or refer to a specialist who can assess, the presence of nasal telangiectasias and/or oral mucosal telangiectasias in patients who have a history of recurrent bilateral nosebleeds or a family history of recurrent nosebleeds to diagnose hereditary hemorrhagic telangiectasia syndrome. (13) The clinician should educate patients with nosebleeds and their caregivers about preventive measures for nosebleeds, home treatment for nosebleeds, and indications to seek additional medical care. (14) The clinician or designee should document the outcome of intervention within 30 days or document transition of care in patients who had a nosebleed treated with nonresorbable packing, surgery, or arterial ligation/embolization. The policy level for the following recommendation, about examination of the nasal cavity and nasopharynx using nasal endoscopy, was an option: (7b) The clinician may perform, or may refer to a clinician who can perform, nasal endoscopy to examine the nasal cavity and nasopharynx in patients with epistaxis that is difficult to control or when there is concern for unrecognized pathology contributing to epistaxis.

Clinical Practice Guideline: Nosebleed (Epistaxis) Executive Summary.

OBJECTIVE: Nosebleed, also known as epistaxis, is a common problem that occurs at some point in at least 60% of people in the United States. While the great majority of nosebleeds are limited in severity and duration, about 6% of people who experience nosebleeds will seek medical attention. For the purposes of this guideline, we define the target patient with a nosebleed as a patient with bleeding from the nostril, nasal cavity, or nasopharynx that is sufficient to warrant medical advice or care. This includes bleeding that is severe, persistent, and/or recurrent, as well as bleeding that impacts a patient's quality of life. Interventions for nosebleeds range from self-treatment and home remedies to more intensive procedural interventions in medical offices, emergency departments, hospitals, and operating rooms. Epistaxis has been estimated to account for 0.5% of all emergency department visits and up to one-third of all otolaryngology-related emergency department encounters. Inpatient hospitalization for aggressive treatment of severe nosebleeds has been reported in 0.2% of patients with nosebleeds. PURPOSE: The primary purpose of this multidisciplinary guideline is to identify quality improvement opportunities in the management of nosebleeds and to create clear and actionable recommendations to implement these opportunities in clinical practice. Specific goals of this guideline are to promote best practices, reduce unjustified variations in care of patients with nosebleeds, improve health outcomes, and minimize the potential harms of nosebleeds or interventions to treat nosebleeds. The target patient for the guideline is any individual aged ≥3 years with a nosebleed or history of nosebleed who needs medical treatment or seeks medical advice. The target audience of this guideline is clinicians who evaluate and treat patients with nosebleed. This includes primary care providers such as family medicine physicians, internists, pediatricians, physician assistants, and nurse practitioners. It also includes specialists such as emergency medicine providers, otolaryngologists, interventional radiologists/neuroradiologists and neurointerventionalists, hematologists, and cardiologists. The setting for this guideline includes any site of evaluation and treatment for a patient with nosebleed, including ambulatory medical sites, the emergency department, the inpatient hospital, and even remote outpatient encounters with phone calls and telemedicine. Outcomes to be considered for patients with nosebleed include control of acute bleeding, prevention of recurrent episodes of nasal bleeding, complications of treatment modalities, and accuracy of diagnostic measures. This guideline addresses the diagnosis, treatment, and prevention of nosebleed. It will focus on nosebleeds that commonly present to clinicians with phone calls, office visits, and emergency room encounters. This guideline discusses first-line treatments such as nasal compression, application of vasoconstrictors, nasal packing, and nasal cautery. It also addresses more complex epistaxis management, which includes the use of endoscopic arterial ligation and interventional radiology procedures. Management options for 2 special groups of patients, patients with hemorrhagic telangiectasia syndrome (HHT) and patients taking medications that inhibit coagulation and/or platelet function, are included in this guideline. This guideline is intended to focus on evidence-based quality improvement opportunities judged most important by the working group. It is not intended to be a comprehensive, general guide for managing patients with nosebleed. In this context, the purpose is to define useful actions for clinicians, generalists, and specialists from a variety of disciplines to improve quality of care. Conversely, the statements in this guideline are not intended to limit or restrict care provided by clinicians based upon their experience and assessment of individual patients. ACTION STATEMENTS: The guideline development group made recommendations for the following key action statements: (1) At the time of initial contact, the clinician should distinguish the nosebleed patient who requires prompt management from the patient who does not. (2) The clinician should treat active bleeding for patients in need of prompt management with firm sustained compression to the lower third of the nose, with or without the assistance of the patient or caregiver, for 5 minutes or longer. (3a) For patients in whom bleeding precludes identification of a bleeding site despite nasal compression, the clinician should treat ongoing active bleeding with nasal packing. (3b) The clinician should use resorbable packing for patients with a suspected bleeding disorder or for patients who are using anticoagulation or antiplatelet medications. (4) The clinician should educate the patient who undergoes nasal packing about the type of packing placed, timing of and plan for removal of packing (if not resorbable), postprocedure care, and any signs or symptoms that would warrant prompt reassessment. (5) The clinician should document factors that increase the frequency or severity of bleeding for any patient with a nosebleed, including personal or family history of bleeding disorders, use of anticoagulant or antiplatelet medications, or intranasal drug use. (6) The clinician should perform anterior rhinoscopy to identify a source of bleeding after removal of any blood clot (if present) for patients with nosebleeds. (7a) The clinician should perform, or should refer to a clinician who can perform, nasal endoscopy to identify the site of bleeding and guide further management in patients with recurrent nasal bleeding, despite prior treatment with packing or cautery, or with recurrent unilateral nasal bleeding. (8) The clinician should treat patients with an identified site of bleeding with an appropriate intervention, which may include 1 or more of the following: topical vasoconstrictors, nasal cautery, and moisturizing or lubricating agents. (9) When nasal cautery is chosen for treatment, the clinician should anesthetize the bleeding site and restrict application of cautery only to the active or suspected site(s) of bleeding. (10) The clinician should evaluate, or refer to a clinician who can evaluate, candidacy for surgical arterial ligation or endovascular embolization for patients with persistent or recurrent bleeding not controlled by packing or nasal cauterization. (11) In the absence of life-threatening bleeding, the clinician should initiate first-line treatments prior to transfusion, reversal of anticoagulation, or withdrawal of anticoagulation/antiplatelet medications for patients using these medications. (12) The clinician should assess, or refer to a specialist who can assess, the presence of nasal telangiectasias and/or oral mucosal telangiectasias in patients who have a history of recurrent bilateral nosebleeds or a family history of recurrent nosebleeds to diagnose hereditary hemorrhagic telangiectasia syndrome (HHT). (13) The clinician should educate patients with nosebleeds and their caregivers about preventive measures for nosebleeds, home treatment for nosebleeds, and indications to seek additional medical care. (14) The clinician or designee should document the outcome of intervention within 30 days or document transition of care in patients who had a nosebleed treated with nonresorbable packing, surgery, or arterial ligation/embolization. The policy level for the following recommendation about examination of the nasal cavity and nasopharynx using nasal endoscopy was an option: (7b) The clinician may perform, or may refer to a clinician who can perform, nasal endoscopy to examine the nasal cavity and nasopharynx in patients with epistaxis that is difficult to control or when there is concern for unrecognized pathology contributing to epistaxis.

Economic evaluation of passive monitoring technology for seniors.

BACKGROUND: Advances such as passive monitoring technology (PMT), which provides holistic supervision of chronically ill and elderly patients, enable and support improved monitoring and observation, thus empowering the growing population of older adults to live more independently while lowering health care expenses. AIMS: This study develops a conceptual model to estimate the potential savings associated with PMT. METHODS: We first develop a conceptual model to identify the main cost variables associated with independent living, focusing on three pathways: (1) PMT, (2) independent living supported by the current standard of care, and (3) facility-based care. We examined the impact on three outcomes [i.e., health care costs, institutional costs, and health-related quality of life (HRQoL)] along each of the three care pathways (i.e., PMT, independent living supported by the standard of care, and facility-based care) and developed a cost-benefit model to calculate the net costs and benefits associated with each care pathway. RESULTS: The cost-benefit model showed savings between approximately $425 per-member per-month (PMPM) for those using PMT compared to those on the standard of care pathway. Sensitivity analysis demonstrated that a 5% increase in nursing home utilization generates cost savings of more than 30% PMPM. DISCUSSION: The total projected cost savings for individuals on the PMT arm are projected to be more than $425 PMPM, with annual savings of $5069 per-person per-year, and over $5.1 million for a target population of 1000 individuals. CONCLUSIONS: The cost calculations in our cost-benefit simulation model clearly demonstrate the value of PMT and show the potential value to payers and integrated delivery systems in offering PMT to individuals who are likely to benefit the most from the services.

Home Biofeedback for the Treatment of Dyssynergic Defecation: Does It Improve Quality of Life and Is It Cost-Effective?

OBJECTIVES: Biofeedback therapy, whether administered at home or in office settings, is effective for dyssynergic defecation (DD). Whether home biofeedback improves quality of life (QOL) and is cost-effective when compared with office biofeedback is unknown. METHODS: QOL was assessed in 8 domains (SF-36) at baseline and after treatment (3 months), alongside economic evaluation during a randomized controlled trial (RCT) comparing home and office biofeedback in patients with DD (Rome III). Costs related to both biofeedback programs were estimated from the hospital financial records, study questionnaires, and electronic medical records. A conversion algorithm (Brazier) was used to calculate the patient's quality-adjusted life years (QALYs) from SF-36 responses. Cost-effectiveness was expressed as incremental costs per QALY between the treatment arms. RESULTS: One hundred patients (96 female patients, 50 in each treatment arm) with DD participated. Six of the 8 QOL domains improved (P < 0.05) in office biofeedback, whereas 4 of the 8 domains improved (P < 0.05) in home biofeedback; home biofeedback was noninferior to office biofeedback. The median cost per patient was significantly lower (P < 0.01) for home biofeedback ($1,112.39; interquartile range (IQR), $826-$1,430) than for office biofeedback ($1,943; IQR, $1,622-$2,369), resulting in a cost difference of $830.11 The median QALY gained during the trial was 0.03 for office biofeedback and 0.07 for home biofeedback (P = NS). The incremental cost-effectiveness ratio was $20,752.75 in favor of home biofeedback. DISCUSSION: Biofeedback therapy significantly improves QOL in patients with DD regardless of home or office setting. Home biofeedback is a cost-effective treatment option for DD compared with office biofeedback, and it offers the potential of treating many more patients in the community.

Implementation of a Socio-structural Demonstration Project to Improve HIV Outcomes Among Young Black Men in the Deep South.

BACKGROUND: We describe the background, rationale, intervention components, and formative results of a demonstration project aimed to ameliorate five socio-structural barriers to HIV services for young Black men aged 18-29 living with and at risk for HIV in Louisiana. METHODS: The interventions and activities consisted of (1) five person-centered approaches to enhance linkage to HIV services and improve socio-economic outcomes; (2) the implementation of systematic mystery shopping tests to document instances of housing discrimination; (3) the development and implementation of a multi-prong communications campaign to increase knowledge about the signs of housing discrimination and community resources among young Black men who have sex with men (YBMSM); (4) the integration of HIV/STI services and lesbian, gay, bisexual, and trans (LGBT)-inclusive events on Historically Black Colleges and Universities (HBCUs); and (5) the development of a safe space for YBMSM. A multi-method approach was used to evaluate the outcomes of the different interventions. RESULTS: The majority (62%) of participants living with HIV were linked to HIV care and 49% had achieved viral suppression. More than 40% of participants were employed during the project. Thirty-seven percent (37%) of the mystery shopping tests showed definite or possible signs of housing discrimination. The housing campaign's duration was limited with unknown long-term impact among YBMSM. Fifteen cases of syphilis were identified during two HBCU events. A safe space was specifically created for YBMSM at a community-based organization. CONCLUSION: Multi-component holistic health interventions are needed to improve HIV outcomes and curb the high HIV rates among young Black men, particularly YBMSM in the United States and the Deep South.

A Longitudinal Analysis of Antiretroviral Adherence Among Young Black Men Who Have Sex With Men.

PURPOSE: Young black men who have sex with men (YBMSM) experience poorer antiretroviral therapy (ART) medication adherence relative to their white counterparts. However, few studies have longitudinally examined factors that may correlate with various classifications of ART adherence among this population, which was the primary aim of this study. METHODS: Project nGage was a randomized controlled trial conducted across five Chicago clinics from 2012 to 2015. Survey and medical records data were collected at baseline and 3- and 12-month periods to assess whether psychological distress, HIV stigma, substance use, family acceptance, social support, and self-efficacy predicted ART medication adherence among 92 YBMSM ages 16-29 years. RESULTS: Major results controlling for the potential effects of age, education level, employment, and intervention condition indicated that participants with high versus low medication adherence were less likely to report daily/weekly alcohol or marijuana use, had higher family acceptance, and exhibited greater self-efficacy. CONCLUSIONS: These findings identity important factors that can be targeted in clinical and program interventions to help improve ART medication adherence for YBMSM.

Patterns of user disclosure of complementary and alternative medicine (CAM) use.

OBJECTIVE: To investigate patterns of complementary and alternative medicine (CAM) use disclosure across medical and sociobehavioral factors and to provide a model that takes into account factors in explaining those patterns. SUBJECTS: A total of 21,849 CAM use episodes from 7347 respondents in the 2007 US National Health Interview Survey which involves the latest survey on CAM use. RESEARCH DESIGN: Respondents were a representative sample of US national population. Logistic hierarchical linear models specify how characteristics of users and their CAM use episodes influence user disclosure behaviors. RESULTS: At the individual level, users were more likely to disclose CAM use to health care professionals when they had health problems and when they were insured. At the episode level, CAM use episodes were more likely to be disclosed when they were intended to treat a specific medical condition and recommended by a health professional. Disclosure rates were high among most susceptible users (ie, sick people intending to treat specific conditions with CAM) and among the biologically based CAM modalities (eg, herbal supplements) that are most likely to produce adverse interactions with conventional biomedical treatments. CONCLUSIONS: User disclosure was affected not only by users' demographic and socioeconomic characteristics but also by episode-specific factors. Efforts to improve provider-user communication of CAM use should consider the varying effects of these factors.

Honokiol produces anti-neoplastic effects on melanoma cells in vitro.

BACKGROUND: Melanoma continues to be a therapeutic challenge for the medical community owing to the scarcity of effective agents available to treat the disease. Honokiol, a traditional Chinese herb, has been proven to have anti-cancer effects in various cell types, therefore we hypothesized it may have similar cytotoxic capabilities against melanoma cells in vitro. METHODS: Two cell lines, SK-MEL2 and MeWo, were grown in culture and exposed to increasing doses of Honokiol. Cell proliferation, cytochrome c release into the cytosol, intra-cellular caspase activity, and mitochondrial depolarization were then evaluated after treatment with honokiol. RESULTS: Melanoma cells in culture underwent cell death, had increased cytosolic cytochrome c, showed greater caspase activity, and demonstrated increased mitochondrial depolarization after treatment when compared to controls. CONCLUSIONS: It appears that honokiol is an effective inhibitor of cultured human melanoma cells.

Self-pacing as a protective mechanism against the effects of heat stress.

OBJECTIVE: Self-pacing or avoidance of physiological strain by adjustment of work rate may be an important protective behaviour for manual workers in severe thermal conditions. Data were gathered at a number of industrial sites in the United Arab Emirates to assess whether self-pacing takes place in these workers. METHODS: Heart rate and aural temperature were monitored in 150 subjects for 12 h daily over 2 consecutive days. Environmental parameters were measured for quantification of heat stress by the thermal work limit. RESULTS: There was no evidence of an effect of variation in environmental thermal stress on either average working heart rate or aural temperature. CONCLUSION: These studies provide evidence that self-pacing is a protective response to working in heat which does not require a highly informed workforce; recognition of this should form part of a holistic approach to management of heat stress in hot climates.

Pterostilbene inhibits pancreatic cancer in vitro.

INTRODUCTION: Stilbenes are phenolic compounds present in grapes and blueberries. Resveratrol, a naturally occurring compound present in grapes, has been shown to have potent antioxidant properties as well as an ability to induce apoptosis. Resveratrol has also been reported to have significant inhibitory effects against a variety of primary tumors including breast, colon, and prostate. Pterostilbene, a naturally occurring analogue of resveratrol found in blueberries, also has antioxidant and antiproliferative properties. It is also substantially more bioavailable orally than resveratrol. These effects have not been studied in pancreatic cancer. We hypothesized that pterostilbene would inhibit pancreatic cancer cell growth in vitro. MATERIALS AND METHODS: Two pancreatic cancer cell lines (MIA PaCa and PANC-1) were cultured using standard techniques. Cells were treated with graduated doses of pterostilbene ranging from 10 to 100 microM. Cell viability was measured by MTT at 24, 48, and 72 h. RESULTS: Pterostilbene decreases cell viability in both cancer cell lines in a concentration- and time-dependent manner. Higher doses (75-100 microM) caused a significant reduction in cell viability at 24 and 48 h. However, by 72 h, all tested concentrations of pterostilbene (10 to 100 microM) resulted in significantly reduced cell viability in both pancreatic cancer cell lines in a dose-dependent fashion. Pterostilbene caused a dose-dependent 10-63% inhibition in MIA PaCa-2 cells and 10-75% inhibition in PANC-1 cells. DISCUSSION: Treatment of pancreatic cancer cells in vitro with Pterostilbene leads to inhibition of cell proliferation and/or cell death, cell cycle arrrest, mitochondrial membrane depolarization, and activation of effector caspases. This naturally occurring agent may have a role in treating pancreatic cancer. CONCLUSIONS: Pterostilbene inhibits the growth of pancreatic cancer in vitro. Further, in vitro mechanistic studies and in vivo experiments are warranted to determine its potential for the treatment of pancreatic cancer.

Pterostilbene inhibits lung cancer through induction of apoptosis.

BACKGROUND: Lung cancer remains the leading cause of cancer mortality in the United States. Resveratrol is a potent antioxidant found in grapes that inhibits several types of cancer, including lung cancer. Herein, we investigated the effects of pterostilbene, an analog of resveratrol found in blueberries, on lung cancer, in vitro. We hypothesized that pterostilbene would inhibit lung cancer cell growth in vitro by a pro-apoptotic mechanism. METHODS: Two lung cancer cell lines (NCI-H460 and SK-MES-1) were cultured using standard techniques. Cells were treated with increasing doses of pterostilbene (10-100 microM). Cell viability was measured at 24, 48, and 72h using a MTT assay. Apo-ONE Caspase-3/7 assay was used to evaluate caspase activity. T-test and two-way ANOVA were used for statistical analysis. RESULTS: Pterostilbene significantly decreased cell viability in lung cancer cells in a concentration- and time-dependent manner (P<0.001). Concentrations greater than 20 microM of pterostilbene produced significant growth inhibition by 72h (P<0.001). Apoptosis and caspase-3/7 activity were significantly increased by pterostilbene treatment (P<0.05). CONCLUSIONS: Pterostilbene inhibits growth via apoptosis induction in vitro. Further in vitro mechanistic studies and in vivo experiments are warranted to determine the potential role for pterostilbene in lung cancer treatment or prevention.

Pterostilbene inhibits breast cancer in vitro through mitochondrial depolarization and induction of caspase-dependent apoptosis.

BACKGROUND: Epidemiologic studies suggest that diets high in fruits and vegetables reduce cancer risk. Resveratrol, a compound present in grapes, has been shown to inhibit a variety of primary tumors. Pterostilbene, an analogue of resveratrol found in blueberries, has both antioxidant and antiproliferative properties. We hypothesized that pterostilbene would induce apoptosis and inhibit breast cancer cell growth in vitro. METHODS: Breast cancer cells were treated with graduated doses of pterostilbene. Cell viability was measured by MTT assay. Apoptosis was evaluated via DNA fragmentation assay and TUNEL assay. Apo-ONE caspase-3/7 assay was used to evaluate caspase activity. Flow cytometry was used to evaluate mitochondrial depolarization, superoxide formation, and cell cycle. Student's t-test and two-way ANOVA with Bonferroni posttests were utilized for statistical analysis. RESULTS: Pterostilbene decreased breast cancer cell viability in a concentration- and time-dependent manner. Pterostilbene treatment increased caspase-3/7 activity and apoptosis in both cell lines. Caspase-3/7 inhibitors completely reversed pterostilbene's effects on cell viability. Pterostilbene treatment triggered mitochondrial depolarization, increased superoxide anion, and caused alteration in cell cycle. CONCLUSIONS: Pterostilbene treatment inhibits the growth of breast cancer in vitro through caspase-dependent apoptosis. Mitochondrial membrane depolarization and increased superoxide anion may contribute to the activation downstream effector caspases. Caspase inhibition leads to complete reversal of pterostilbene's effect on cell viability. Further in vitro mechanistic studies and in vivo experiments are warranted to determine its potential for the treatment of breast cancer.

Effects of pterostilbene on melanoma alone and in synergy with inositol hexaphosphate.

BACKGROUND: Pterostilbene and inositol-6-phosphate (IP6) have been shown to inhibit melanoma growth in vitro. However, pterostilbene's mechanism of action has not been clearly demonstrated. We aimed to further investigate the mechanism of action for pterostilbene and to determine whether combination treatment with IP6 produced synergistic growth inhibition. METHODS: Melanoma cells were treated with increasing doses of pterostilbene, IP6, or combinations thereof. Cell viability was measured at 24 hours, 48 hours, and 72 hours using a MTT assay. Caspase activity and vascular endothelial growth factor (VEGF) production were measured using enzyme-linked immunosorbent assay (ELISA). Analysis of variance (ANOVA) and t tests were used for statistical analysis. RESULTS: Pterostilbene inhibits melanoma growth in vitro in association with increased effector caspase activity. Combination treatment with inositol hexaphosphate produces synergistic growth inhibition, greater than either treatment alone. CONCLUSIONS: Pterostilbene produces caspase-dependent apoptosis in melanoma cell lines. Combination treatment with IP6 produces synergistic growth inhibition. Both compounds have significant potential for a therapeutic role in the treatment of melanoma.