Screening for Latent Tuberculosis Infection in Adults: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance: Latent tuberculosis infection (LTBI) can progress to active tuberculosis disease, causing morbidity and mortality. Objective: To review the evidence on benefits and harms of screening for and treatment of LTBI in adults to inform the US Preventive Services Task Force (USPSTF). Data Sources: PubMed/MEDLINE, Cochrane Library, and trial registries through December 3, 2021; references; experts; literature surveillance through January 20, 2023. Study Selection: English-language studies of LTBI screening, LTBI treatment, or accuracy of the tuberculin skin test (TST) or interferon-gamma release assays (IGRAs). Studies of LTBI screening and treatment for public health surveillance or disease management were excluded. Data Extraction and Synthesis: Dual review of abstracts, full-text articles, and study quality; qualitative synthesis of findings; meta-analyses conducted when a sufficient number of similar studies were available. Main Outcomes and Measures: Screening test accuracy; development of active tuberculosis disease, transmission, quality of life, mortality, and harms. Results: A total of 113 publications were included (112 studies; N = 69 009). No studies directly evaluated the benefits and harms of screening. Pooled estimates for sensitivity of the TST were 0.80 (95% CI, 0.74-0.87) at the 5-mm induration threshold, 0.81 (95% CI, 0.76-0.87) at the 10-mm threshold, and 0.60 (95% CI, 0.46-0.74) at the 15-mm threshold. Pooled estimates for sensitivity of IGRA tests ranged from 0.81 (95% CI, 0.79-0.84) to 0.90 (95% CI, 0.87-0.92). Pooled estimates for specificity of screening tests ranged from 0.95 to 0.99. For treatment of LTBI, a large (n = 27 830), good-quality randomized clinical trial found a relative risk (RR) for progression to active tuberculosis at 5 years of 0.35 (95% CI, 0.24-0.52) for 24 weeks of isoniazid compared with placebo (number needed to treat, 112) and an increase in hepatotoxicity (RR, 4.59 [95% CI, 2.03-10.39]; number needed to harm, 279). A previously published meta-analysis reported that multiple regimens were efficacious compared with placebo or no treatment. Meta-analysis found greater risk for hepatotoxicity with isoniazid than with rifampin (pooled RR, 4.22 [95% CI, 2.21-8.06]; n = 7339). Conclusions and Relevance: No studies directly evaluated the benefits and harms of screening for LTBI compared with no screening. TST and IGRAs were moderately sensitive and highly specific. Treatment of LTBI with recommended regimens reduced the risk of progression to active tuberculosis. Isoniazid was associated with higher rates of hepatotoxicity than placebo or rifampin.

Screening for Atrial Fibrillation: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance: Atrial fibrillation (AF), the most common arrhythmia, increases the risk of stroke. Objective: To review the evidence on screening for AF in adults without prior stroke to inform the US Preventive Services Task Force. Data Sources: PubMed, Cochrane Library, and trial registries through October 5, 2020; references, experts, and literature surveillance through October 31, 2021. Study Selection: Randomized clinical trials (RCTs) of screening among asymptomatic persons without known AF or prior stroke; test accuracy studies; RCTs of anticoagulation among persons with AF; systematic reviews; and observational studies reporting harms. Data Extraction and Synthesis: Two reviewers assessed titles/abstracts, full-text articles, and study quality and extracted data; when at least 3 similar studies were available, meta-analyses were conducted. Main Outcomes and Measures: Detection of undiagnosed AF, test accuracy, mortality, stroke, stroke-related morbidity, and harms. Results: Twenty-six studies (N = 113 784) were included. In 1 RCT (n = 28 768) of twice-daily electrocardiography (ECG) screening for 2 weeks, the likelihood of a composite end point (ischemic stroke, hemorrhagic stroke, systemic embolism, all-cause mortality, and hospitalization for bleeding) was lower in the screened group over 6.9 years (hazard ratio, 0.96 [95% CI, 0.92-1.00]; P = .045), but that study had numerous limitations. In 4 RCTs (n = 32 491), significantly more AF was detected with intermittent and continuous ECG screening compared with no screening (risk difference range, 1.0%-4.8%). Treatment with warfarin over a mean of 1.5 years in populations with clinical, mostly persistent AF was associated with fewer ischemic strokes (pooled risk ratio [RR], 0.32 [95% CI, 0.20-0.51]; 5 RCTs; n = 2415) and lower all-cause mortality (pooled RR, 0.68 [95% CI, 0.50-0.93]) compared with placebo. Treatment with direct oral anticoagulants was also associated with lower incidence of stroke (adjusted odds ratios range, 0.32-0.44) in indirect comparisons with placebo. The pooled RR for major bleeding for warfarin compared with placebo was 1.8 (95% CI, 0.85-3.7; 5 RCTs; n = 2415), and the adjusted odds ratio for major bleeding for direct oral anticoagulants compared with placebo or no treatment ranged from 1.38 to 2.21, but CIs did not exclude a null effect. Conclusions and Relevance: Although screening can detect more cases of unknown AF, evidence regarding effects on health outcomes is limited. Anticoagulation was associated with lower risk of first stroke and mortality but with increased risk of major bleeding, although estimates for this harm are imprecise; no trials assessed benefits and harms of anticoagulation among screen-detected populations.

Screening for Atrial Fibrillation With Electrocardiography: Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance: Atrial fibrillation is the most common arrhythmia and increases the risk of stroke. Objective: To review the evidence on screening for nonvalvular atrial fibrillation with electrocardiography (ECG) and stroke prevention treatment in asymptomatic adults 65 years or older to inform the US Preventive Services Task Force. Data Sources: MEDLINE, Cochrane Library, and trial registries through May 2017; references; experts; literature surveillance through June 6, 2018. Study Selection: English-language randomized clinical trials (RCTs), prospective cohort studies evaluating detection rates of atrial fibrillation or harms of screening, and systematic reviews evaluating stroke prevention treatment. Eligible treatment studies compared warfarin, aspirin, or novel oral anticoagulants (NOACs) with placebo or no treatment. Studies were excluded that focused on persons with a history of cardiovascular disease. Data Extraction and Synthesis: Dual review of abstracts, full-text articles, and study quality. When at least 3 similar studies were available, random-effects meta-analyses were conducted. Main Outcomes and Measures: Detection of previously undiagnosed atrial fibrillation, mortality, stroke, stroke-related morbidity, and harms. Results: Seventeen studies were included (n = 135 300). No studies evaluated screening compared with no screening and focused on health outcomes. Systematic screening with ECG identified more new cases of atrial fibrillation than no screening (absolute increase, from 0.6% [95% CI, 0.1%-0.9%] to 2.8% [95% CI, 0.9%-4.7%] over 12 months; 2 RCTs, n = 15 803), but a systematic approach using ECG did not detect more cases than an approach using pulse palpation (2 RCTs, n = 17 803). For potential harms, no eligible studies compared screening with no screening. Warfarin (mean, 1.5 years) was associated with a reduced risk of ischemic stroke (relative risk [RR], 0.32 [95% CI, 0.20-0.51]) and all-cause mortality (RR, 0.68 [95% CI, 0.50-0.93]) and with increased risk of bleeding (5 trials, n = 2415). Participants in treatment trials were not screen detected, and most had long-standing persistent atrial fibrillation. A network meta-analysis reported that NOACs were associated with a significantly lower risk of a composite outcome of stroke and systemic embolism (adjusted odds ratios compared with placebo or control ranged from 0.32-0.44); the risk of bleeding was increased (adjusted odds ratios, 1.4-2.2), but confidence intervals were wide and differences between groups were not statistically significant. Conclusions and Relevance: Although screening with ECG can detect previously unknown cases of atrial fibrillation, it has not been shown to detect more cases than screening focused on pulse palpation. Treatments for atrial fibrillation reduce the risk of stroke and all-cause mortality and increase the risk of bleeding, but trials have not assessed whether treatment of screen-detected asymptomatic older adults results in better health outcomes than treatment after detection by usual care or after symptoms develop.

Serologic Screening for Genital Herpes: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.

This systematic review to support the 2023 US Preventive Services Task Force Recommendation Statement on serologic screening for genital herpes summarizes published evidence on the benefits and harms of screening and interventions for genital herpes in asymptomatic sexually active adolescents, adults, and pregnant persons with no clinical history of genital herpes.

Screening for Cardiovascular Disease Risk With Resting or Exercise Electrocardiography: Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance: Cardiovascular disease (CVD) is the leading cause of death in the United States. Objective: To review the evidence on screening asymptomatic adults for CVD risk using electrocardiography (ECG) to inform the US Preventive Services Task Force. Data Sources: MEDLINE, Cochrane Library, and trial registries through May 2017; references; experts; literature surveillance through April 4, 2018. Study Selection: English-language randomized clinical trials (RCTs); prospective cohort studies reporting reclassification, calibration, or discrimination that compared risk assessment using ECG plus traditional risk factors vs traditional risk factors alone. For harms, additional study designs were eligible. Studies of persons with symptoms or a CVD diagnosis were excluded. Data Extraction and Synthesis: Dual review of abstracts, full-text articles, and study quality; qualitative synthesis of findings. Main Outcomes and Measures: Mortality, cardiovascular events, reclassification, calibration, discrimination, and harms. Results: Sixteen studies were included (N = 77 140). Two RCTs (n = 1151) found no significant improvement for screening with exercise ECG (vs no screening) in adults aged 50 to 75 years with diabetes for the primary cardiovascular composite outcomes (hazard ratios, 1.00 [95% CI, 0.59-1.71] and 0.85 [95% CI, 0.39-1.84] for each study). No RCTs evaluated screening with resting ECG. Evidence from 5 cohort studies (n = 9582) showed that adding exercise ECG to traditional risk factors such as age, sex, current smoking, diabetes, total cholesterol level, and high-density lipoprotein cholesterol level produced small improvements in discrimination (absolute improvements in area under the curve [AUC] or C statistics, 0.02-0.03, reported by 3 studies); whether calibration or appropriate risk classification improves is uncertain. Evidence from 9 cohort studies (n = 66 407) showed that adding resting ECG to traditional risk factors produced small improvements in discrimination (absolute improvement in AUC or C statistics, 0.001-0.05) and appropriate risk classification for prediction of multiple cardiovascular outcomes, although evidence was limited by imprecision, quality, considerable heterogeneity, and inconsistent use of risk thresholds used for clinical decision making. Total net reclassification improvements ranged from 3.6% (2.7% event; 0.6% nonevent) to 30% (17% event; 19% nonevent) for studies using the Framingham Risk Score or Pooled Cohort Equations base models. Evidence on potential harms (eg, from subsequent angiography or revascularization) in asymptomatic persons was limited. Conclusions and Relevance: RCTs of screening with exercise ECG found no improvement in health outcomes, despite focusing on higher-risk populations with diabetes. The addition of resting ECG to traditional risk factors accurately reclassified persons, but evidence for this finding had many limitations. The frequency of harms from screening is uncertain.

A mindful self-compassion videoconference intervention for nationally recruited posttreatment young adult cancer survivors: feasibility, acceptability, and psychosocial outcomes.

PURPOSE: Young adult (YA) cancer survivors report substantial distress, social isolation, and body image concerns that can impede successful reintegration into life years after treatment completion. Mindful Self-Compassion (MSC) interventions focus on developing mindfulness and self-compassion for managing distress, hardships, and perceived personal inadequacies. An MSC intervention would be beneficial in supporting YA survivors' management of psychosocial challenges that arise in survivorship; however, a telehealth intervention modality is essential for reaching this geographically dispersed population. We conducted a single-arm feasibility study of an MSC 8-week videoconference intervention for nationally recruited YA survivors (ages 18-29). METHODS: The MSC intervention was group-based, 90-minute videoconference sessions, held weekly over 8 weeks, with audio-supplemented home practice. Feasibility and acceptability were assessed via attendance rate and an intervention satisfaction scale. Baseline to post-intervention changes in psychosocial outcomes (body image, anxiety, depression, social isolation, posttraumatic growth, resilience, self-compassion, mindfulness) were assessed using paired t tests and Cohen's d effect sizes. RESULTS: Thirty-four participants were consented and 25 attended a videoconference group. Feasibility was established with 84% attending at least six of the eight sessions, and intervention acceptability was high (M = 4.36, SD = 0.40, score range = 1-5). All psychosocial outcomes, except for resilience, demonstrated significant changes (p < 0.002), with medium to large effect sizes (Cohen's d > 0.5). CONCLUSION: YA survivors are interested in receiving an MSC videoconference intervention. Feasibility, acceptance, and potential psychosocial benefits of the intervention were demonstrated. Findings can be applied toward the design of an efficacy randomized controlled trial to improve quality of life for YA survivors in transition after cancer treatment.

Comparative Benefits and Harms of Antidepressant, Psychological, Complementary, and Exercise Treatments for Major Depression: An Evidence Report for a Clinical Practice Guideline From the American College of Physicians.

BACKGROUND: Primary care patients and clinicians may prefer options other than second-generation antidepressants for the treatment of major depressive disorder (MDD). The comparative benefits and harms of antidepressants and alternative treatments are unclear. PURPOSE: To compare the benefits and harms of second-generation antidepressants and psychological, complementary and alternative medicine (CAM), and exercise treatments as first- and second-step interventions for adults with acute MDD. DATA SOURCES: English-, German-, and Italian-language studies from multiple electronic databases (January 1990 to September 2015); trial registries and gray-literature databases were used to identify unpublished research. STUDY SELECTION: Two investigators independently selected comparative randomized trials of at least 6 weeks' duration on health outcomes of adult outpatients; nonrandomized studies were eligible for harms. DATA EXTRACTION: Reviewers abstracted data on study design, participants, interventions, and outcomes; rated the risk of bias; and graded the strength of evidence. A senior reviewer confirmed data and ratings. DATA SYNTHESIS: 45 trials met inclusion criteria. On the basis of moderate-strength evidence, cognitive behavioral therapy (CBT) and antidepressants led to similar response rates (relative risk [RR], 0.90 [95% CI, 0.76 to 1.07]) and remission rates (RR, 0.98 [CI, 0.73 to 1.32]). In trials, antidepressants had higher risks for adverse events than most other treatment options; no information from nonrandomized studies was available. The evidence was too limited to make firm conclusions about differences in the benefits and harms of antidepressants compared with other treatment options as first-step therapies for acute MDD. For second-step therapies, different switching and augmentation strategies provided similar symptom relief. LIMITATION: High dropout rates, dosing inequalities, small sample sizes, and poor assessment of adverse events limit confidence in the evidence. CONCLUSION: Given their similar efficacy, CBT and antidepressants are both viable choices for initial treatment of MDD. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.

Common Herbal Dietary Supplement-Drug Interactions.

Nearly 25% of U.S. adults report concurrently taking a prescription medication with a dietary supplement. Some supplements, such as St. John's wort and goldenseal, are known to cause clinically important drug interactions and should be avoided by most patients receiving any pharmacologic therapy. However, many other supplements are predicted to cause interactions based only on in vitro studies that have not been confirmed or have been refuted in human clinical trials. Some supplements may cause interactions with a few medications but are likely to be safe with other medications (e.g., curcumin, echinacea, garlic, Asian ginseng, green tea extract, kava kava). Some supplements have a low likelihood of drug interactions and, with certain caveats, can safely be taken with most medications (e.g., black cohosh, cranberry, ginkgo, milk thistle, American ginseng, saw palmetto, valerian). Clinicians should consult reliable dietary supplement resources, or clinical pharmacists or pharmacologists, to help assess the safety of specific herbal supplement-drug combinations. Because most patients do not disclose supplement use to clinicians, the most important strategy for detecting herb-drug interactions is to develop a trusting relationship that encourages patients to discuss their dietary supplement use.

Clinical utility of curcumin extract.

Turmeric root has been used medicinally in China and India for thousands of years. The active components are thought to be the curcuminoids, primarily curcumin, which is commonly available worldwide as a standardized extract. This article reviews the pharmacology of curcuminoids, their use and efficacy, potential adverse effects, and dosage and standardization. Preclinical studies point to mechanisms of action that are predominantly anti-inflammatory and antineoplastic, while early human clinical trials suggest beneficial effects for dyspepsia, peptic ulcer, inflammatory bowel disease, rheumatoid arthritis, osteoarthritis, uveitis, orbital pseudotumor, and pancreatic cancer. Curcumin is well-tolerated; the most common side effects are nausea and diarrhea. Theoretical interactions exist due to purported effects on metabolic enzymes and transport proteins, but clinical reports do not support any meaningful interactions. Nonetheless, caution, especially with chemotherapy agents, is advised. Late-phase clinical trials are still needed to confirm most beneficial effects.

Healthcare Professionals' Perspectives on Improving Dietary Supplement Documentation in the Electronic Medical Record: Current Challenges and Opportunities to Enhance Quality of Care and Patient Safety.

Background: Around half the US population uses dietary supplements (DS), and concomitant use with medications is common. Many DS include bioactive substances that can interact with medications; therefore, accurate tracking is critical for patient safety. Unfortunately, documentation of patients' DS use is often missing or incomplete in the electronic medical record (EMR), leaving patients susceptible to potential adverse events. Novel approaches to assist healthcare professionals (HCPs) in capturing patients' DS use are needed. Objective: To assess HCPs' perspectives on challenges and facilitators of DS documentation in the EMR and their opinions on a proposed mHealth application (app) to aid in DS capture. Methods: HCPs, recruited from professional networks, largely in North Carolina, using purposive sampling, took part in semi-structured interviews. We inquired about HCPs' experiences with DS documentation in the EMR and their opinions about our proposed mHealth app. Interviews were recorded, transcribed, and coded. Thematic analysis included deductive codes based on the interview guide, and inductive codes that emerged during transcript review. Results: HCPs (N = 30) included 60% females, mean age 46 ± 10; 70% White. Pharmacists (20%), nurses (17%), and physicians (17%) were the most represented professions. Years in practice ranged from 3-35 years. Most HCPs were concerned about DS safety and potential supplement-drug interactions, and cited several barriers to accurate EMR DS documentation including time constraints, database inconsistencies, and poor patient-HCP communication about DS. HCPs' views on our proposed mHealth app were generally positive. They expressed that our proposed mHealth app could streamline documentation processes and enhance patient-provider communication. HCPs expressed desire for a high-quality mHealth app that includes access to evidence-based DS information, integrates with the EMR, and does not increase time burdens. Conclusion: HCPs believe documentation of patients' DS use is important but not accurately captured in the EMR. Support was expressed for our proposed barcode-scanning DS mHealth app.

Integrative Oncology Care of Symptoms of Anxiety and Depression in Adults With Cancer: Society for Integrative Oncology-ASCO Guideline.

PURPOSE: To provide evidence-based recommendations to health care providers on integrative approaches to managing anxiety and depression symptoms in adults living with cancer. METHODS: The Society for Integrative Oncology and ASCO convened an expert panel of integrative oncology, medical oncology, radiation oncology, surgical oncology, palliative oncology, social sciences, mind-body medicine, nursing, methodology, and patient advocacy representatives. The literature search included systematic reviews, meta-analyses, and randomized controlled trials published from 1990 through 2023. Outcomes of interest included anxiety or depression symptoms as measured by validated psychometric tools, and adverse events. Expert panel members used this evidence and informal consensus with the Guidelines into Decision Support methodology to develop evidence-based guideline recommendations. RESULTS: The literature search identified 110 relevant studies (30 systematic reviews and 80 randomized controlled trials) to inform the evidence base for this guideline. RECOMMENDATIONS: Recommendations were made for mindfulness-based interventions (MBIs), yoga, relaxation, music therapy, reflexology, and aromatherapy (using inhalation) for treating symptoms of anxiety during active treatment; and MBIs, yoga, acupuncture, tai chi and/or qigong, and reflexology for treating anxiety symptoms after cancer treatment. For depression symptoms, MBIs, yoga, music therapy, relaxation, and reflexology were recommended during treatment, and MBIs, yoga, and tai chi and/or qigong were recommended post-treatment. DISCUSSION: Issues of patient-health care provider communication, health disparities, comorbid medical conditions, cost implications, guideline implementation, provider training and credentialing, and quality assurance of natural health products are discussed. While several approaches such as MBIs and yoga appear effective, limitations of the evidence base including assessment of risk of bias, nonstandardization of therapies, lack of diversity in study samples, and lack of active control conditions as well as future research directions are discussed.Additional information is available at www.asco.org/survivorship-guidelines.

Effect of hawthorn standardized extract on flow mediated dilation in prehypertensive and mildly hypertensive adults: a randomized, controlled cross-over trial.

BACKGROUND: Hawthorn extract has been used for cardiovascular diseases for centuries. Recent trials have demonstrated its efficacy for the treatment of heart failure, and the results of several small trials suggest it may lower blood pressure. However, there is little published evidence to guide its dosing. The blood pressure lowering effect of hawthorn has been linked to nitric oxide-mediated vasodilation. The aim of this study was to investigate the relationship between hawthorn extract dose and brachial artery flow mediated dilation (FMD), an indirect measure of nitric oxide release. METHODS: We used a four-period cross-over design to evaluate brachial artery FMD in response to placebo or hawthorn extract (standardized to 50 mg oligomeric procyanidin per 250 mg extract). Randomly sequenced doses of hawthorn extract (1000 mg, 1500 mg, and 2500 mg) and placebo were assigned to each participant. Doses were taken twice daily for 3 1/2 days followed by FMD and a 4-day washout before proceeding to the next dosing period. RESULTS: Twenty-one prehypertensive or mildly hypertensive adults completed the study. There was no evidence of a dose-response effect for our main outcome (FMD percent) or any of our secondary outcomes (absolute change in brachial artery diameter and blood pressure). Most participants indicated that if given evidence that hawthorn could lower their blood pressure, they would be likely to use it either in conjunction with or instead of lifestyle modification or anti-hypertensive medications. CONCLUSION: We found no evidence of a dose-response effect of hawthorn extract on FMD. If hawthorn has a blood pressure lowering effect, it is likely to be mediated via an NO-independent mechanism. TRIAL REGISTRATION: This trial has been registered with ClinicalTrials.gov, a service of the U.S. National Institutes of Health: NCT01331486.

Patient Perspectives on the Development of a Novel Mobile Health (mHealth) Application for Dietary Supplement Tracking and Reconciliation-A Qualitative Focus Group Study.

BACKGROUND: More than 170 million adults use dietary supplements (DS) in the United States, which can have both benefit and harm to patient health. DS use is often poorly documented in the medical record and can pose health risks if not properly communicated with providers. Reasons for poor DS documentation include low disclosure rates, time constraints of clinical encounters, and providers' failure to inquire about DS use. This study was conducted to assess patients' views on the facilitators and barriers to using a mobile health (mHealth) application (app) to collect and share DS information with their healthcare providers. METHODS: Utilizing a theory-based conceptual model, we conducted 7 patient focus groups (FGs) to assess opinions on DS safety, provider communication, comfort with technology use, and our proposed mHealth app. Participants were recruited from the general public and through patient advisory groups. Patient views will inform the creation of an mHealth app to improve DS patient-provider communication and tracking and reconciliation in the electronic medical record (EMR). RESULTS: Overall, participants believe their DS information is inaccurately represented in the EMR, leading to safety concerns and negatively impacting overall quality of care. Participants desired an app designed with (1) Health Insurance Portability and Accountability Act (HIPAA) compliance; (2) ease of use for a variety of technical efficacy levels; (3) access to reliable DS information, including a DS-drug interaction checker; and (4) integration with the EMR. CONCLUSION: An app to simplify and improve DS entry and reconciliation was of interest to patients, as long as it maintained health autonomy and privacy and possessed key valuable features.

A phase I evaluation of the effect of curcumin on dose-limiting toxicity and pharmacokinetics of irinotecan in participants with solid tumors.

Curcumin inhibits UDP-glucuronyltransferases, a primary metabolic pathway for cancer chemotherapeutic agents like irinotecan. Concurrent administration of both agents may exacerbate irinotecan toxicity. We conducted this phase I study to determine the safety of concurrent curcumin and irinotecan administration. Ten participants with advanced solid tumors received one of four doses (1, 2, 3, and 4 g) of a curcumin phosphatidylcholine complex (PC) orally daily, and 200 mg/m2 of i.v. infusion irinotecan on days 1 and 15 of a 28-day cycle, to determine the maximum tolerated dose (MTD) of PC. Thirteen participants received 4 g of PC (MTD) to assess the effect on the pharmacokinetic (PK) properties of irinotecan and its metabolites, SN-38 and SN-38G. Irinotecan, SN-38, and SN-38G exposure equivalence with and without curcumin was assessed using area under the plasma concentration-time curves from 0 to 6 h (AUC0-6h ). Safety assessments and disease responses were also evaluated. The combination of irinotecan and PC was well-tolerated. Because there was no dose limiting toxicity, the maximum dose administered (4 g) was defined as the recommended phase II dose of PC. PC did not significantly alter the plasma exposure and other PK properties of irinotecan and its metabolites. There was no apparent increase in the incidence of irinotecan-associated toxicities. The objective response rate was 3/19 (22%, 95% confidence interval [CI]: 5-39%), median progression free survival and overall survival (n = 23) were 4 months (95% CI: 2.9-8.9 months) and 8.4 months (95% CI: 3.7 - not evaluable [NE]), respectively. Future studies are required to evaluate the efficacy of this combination.

Use of Dietary Supplements at a Comprehensive Cancer Center.

OBJECTIVES: The objectives of this study were to define dietary supplement (DS) use by cancer patients and to investigate factors associated with DS use during cancer treatment. METHODS: A cross-sectional survey of adults diagnosed with breast, colorectal, lung, or prostate cancer in 2010-2012 at the University of North Carolina Comprehensive Cancer Center was conducted. Questionnaires were sent to 1794 patients. Phone calls were made to nonrespondents. The authors described type of DS use before, during, and after initial cancer treatment, source of advice on DS use, and used logistic regression to investigate the association of DS use during or after cancer treatment with clinical/sociodemographic characteristics and source of advice. RESULTS: Six hundred and three (34%) patients completed the questionnaires. Nonvitamin nonmineral DS use during initial cancer treatments was common: any cancer treatment (49%), chemotherapy (52%), and radiation therapy (51%). Among patients seeking advice on DS use, 75% reported professional sources, 44% reported media sources, and 47% reported lay sources. DS use during cancer treatment was strongly predicted by prior DS use, followed by prior complementary therapies' use, receiving DS advice from a cancer care provider, being female, and higher education level. CONCLUSION: DS use is common and persists during cancer treatment. Among DS users during treatment, 18% used an herbal supplement, which are likely to carry greater risk of interaction with chemotherapy agents compared with vitamin, mineral, and other supplements. Although many respondents sought DS advice from professional sources, the use of nonprofessional sources remains high.

Complementary and Alternative Medicine Use at a Comprehensive Cancer Center.

BACKGROUND: Complementary and alternative medicine (CAM) use is common among cancer patients, but the majority of CAM studies do not specify the time periods in relation to cancer diagnoses. We sought to define CAM use by cancer patients and investigate factors that might influence changes in CAM use in relation to cancer diagnoses. METHODS: We conducted a cross-sectional survey of adults diagnosed with breast, prostate, lung, or colorectal cancer between 2010 and 2012 at the Lineberger Comprehensive Cancer Center. Questionnaires were sent to 1794 patients. Phone calls were made to nonrespondents. Log binomial/Poisson regressions were used to investigate the association between cancer-related changes in CAM use and conversations about CAM use with oncology providers. RESULTS: We received 603 (33.6 %) completed questionnaires. The mean age (SD) was 64 (11) years; 62% were female; 79% were white; and 98% were non-Hispanic. Respondents reported the following cancer types: breast (47%), prostate (27%), colorectal (14%), lung (11%). Eighty-nine percent reported lifetime CAM use. Eighty-five percent reported CAM use during or after initial cancer treatment, with category-specific use as follows: mind-body medicine 39%, dietary supplements 73%, body-based therapies 30%, and energy medicine 49%. During treatment CAM use decreased for all categories except energy medicine. After treatment CAM use returned to pretreatment levels for most CAMs except chiropractic. Initiation of CAM use after cancer diagnosis was positively associated with a patient having a conversation about CAM use with their oncology provider, mainly driven by patient-initiated conversations. CONCLUSIONS: Consistent with previous studies, CAM use was common among our study population. Conversations about CAM use with oncology providers appeared to influence cessation of mind-body medicine use after cancer diagnosis.

Complementary Therapies for Mental Health Disorders.

Approximately 18% of the US adult population has a mental illness, yet only 13% with mental illness receive any treatment. Although pharmacotherapy and psychotherapy are the mainstays of treatment, treatment discontinuation and failure are common. Skepticism toward such treatments has fueled interest in and use of complementary therapies, such as acupuncture, meditation, and natural products. Many medical providers are unaware of the use of these therapies by their patients, and knowledge of the evidence base for these therapies is often lacking. This article presents current evidence-based recommendations for complementary therapies in the treatment of depression, anxiety, and posttraumatic stress disorder.

Randomized Pharmacokinetic Crossover Study Comparing 2 Curcumin Preparations in Plasma and Rectal Tissue of Healthy Human Volunteers.

Curcumin is poorly absorbed, which is interest in new preparations. However, little is known about variations in its pharmacokinetics and tissue bioavailability between formulations. In this randomized, crossover study we evaluated the relationship between steady-state plasma and rectal tissue curcuminoid concentrations using standard and phosphatidylcholine curcumin extracts. There was no difference in the geometric mean plasma AUCs when adjusted for the 10-fold difference in curcumin dose between the 2 formulations. Phosphatidylcholine curcumin extract yielded only 20% to 30% plasma demethoxycurcumin and bisdemethoxycurcumin conjugates compared to standard extract, yet yielded 20-fold greater hexahydrocurcumin. When adjusting for curcumin dose, tissue curcumin concentrations were 5-fold greater for the phosphatidylcholine extract. Improvements in curcuminoid absorption due to phosphatidylcholine are not uniform across the curcuminoids. Furthermore, curcuminoid exposures in the intestinal mucosa are most likely due to luminal exposure rather than to plasma disposition. Finally, once-daily dosing is sufficient to maintain detectable curcuminoids at steady state in both plasma and rectal tissues.

Comparative Benefits and Harms of Complementary and Alternative Medicine Therapies for Initial Treatment of Major Depressive Disorder: Systematic Review and Meta-Analysis.

OBJECTIVES: To report the comparative benefits and harms of exercise and complementary and alternative medicine (CAM) treatments with second-generation antidepressants (SGA) for major depressive disorder (MDD). DESIGN: Systematic review and meta-analysis. SETTINGS: Outpatient clinics. SUBJECTS: Adults, aged 18 years and older, with MDD receiving an initial treatment attempt with SGA. INTERVENTIONS: Any CAM or exercise intervention compared with an SGA. OUTCOME MEASURES: Treatment response, remission, change in depression rating, adverse events, treatment discontinuation, and treatment discontinuation due to adverse events. RESULTS: We found 22 randomized controlled trials for direct comparisons and 127 trials for network meta-analyses, including trials of acupuncture, omega-3 fatty acids, S-adenosyl methionine, St. John's wort, and exercise. For most treatment comparisons, we found no differences between treatment groups for response and remission. However, the risk of bias of these studies led us to conclude that the strength of evidence for these findings was either low or insufficient. The risk of treatment harms and treatment discontinuation attributed to adverse events was higher for selective serotonin receptor inhibitors than for St. John's wort. CONCLUSIONS: Although we found little difference in the comparative efficacy of most CAM therapies or exercise and SGAs, the overall poor quality of the available evidence base tempers any conclusions that we might draw from those trials. Future trials should incorporate patient-oriented outcomes, treatment expectancy, depressive severity, and harms assessments into their designs; antidepressants should be administered over their full dosage ranges; and larger trials using methods to reduce sampling bias are needed.