3,3-Diindolylmethane (DIM): a nutritional intervention and its impact on breast density in healthy BRCA carriers. A prospective clinical trial.

Women who carry the BRCA mutation are at high lifetime risk of breast cancer, but there is no consensus regarding an effective and safe chemoprevention strategy. A large body of evidence suggests that 3,3-diindolylmethane (DIM), a dimer of indole-3-carbinol found in cruciferous vegetables, can potentially prevent carcinogenesis and tumor development. The primary aim of this prospective single-arm study was to investigate the effect of DIM supplementation on breast density, a recognized predictive factor of breast cancer risk. Participants were 23 healthy female BRCA carriers (median age 47 years; 78% postmenopausal) who were treated with oral DIM 100 mg × 1/day for 1 year. The amount of fibroglandular tissue (FGT) and background parenchymal enhancement (BPE) on magnetic resonance imaging (MRI) performed before and after the intervention was scored by two independent expert radiologists using the Breast Imaging and Reporting Data System. The results showed a decrease in the average score for FGT amount from 2.8 ± 0.8 at the onset to 2.65 ± 0.84 after 1 year (P = 0.031), with no significant change in BPE (P = 0.429). A group of DIM-untreated age- and menopausal-status-matched women from the BRCA clinic did not show a significant change in FGT amount (P = 0.33) or BPE (P = 0.814) in a parallel year. Mean estradiol level decreased from 159 to 102 pmol/l (P = 0.01), and mean testosterone level decreased from 0.42 to 0.31 pmol/l (P = 0.007). Side effects were grade 1. In conclusion, 1 year's supplementation with DIM 100 mg × 1/day in BRCA carriers was associated with a significant decline in FGT amount on MRI. Larger randomized studies are warranted to corroborate these findings.

The role of emotional processing in art therapy (REPAT) for breast cancer patients.

Emotional awareness and acceptance of emotion are associated with improved health in breast cancer (BC) patients. Art therapy (AT) uses visual art-making for expression and communication and has been shown to reduce psychological and physical symptoms in individuals with cancer. A major objective of AT is to encourage increases in emotion processing; however, few studies examine these changes. Purpose: To examine the effect of an eight-week AT group on emotion processing as a mechanism of symptom reduction in women with BC. Design: Randomized clinical trial. Sample: Twenty women diagnosed with breast cancer whom had completed primary treatment. Methods: Participants were randomized to participate in eight-weeks of AT or sham AT, which was a mandala coloring group. Participants answered questionnaires before and after the intervention. We used a Cohen's D calculator for effect sizes and a t-test to examine group differences. Findings: Statistically significant between-group differences in emotional awareness and acceptance of emotion were found after the intervention. We found large effect sizes between groups and over time in acceptance of emotion, emotional awareness and depressive symptoms. Conclusions: We conclude that emotion processing in AT may be a potential mechanism reducing depression and somatic symptoms in cancer patients. Implications for Psychosocial Providers: Art Therapy is a feasible intervention to increase emotional processing. A larger study is required to further examine its effect on psychological and physical symptoms in breast cancer patients.

Identifying Tyrosine Kinase Inhibitor Nonadherence in Chronic Myeloid Leukemia: Subanalysis of TAKE-IT Pilot Study.

BACKGROUND: There are inconsistencies in reports on correlates for nonadherence (NA) to tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia (CML). The diagnostic accuracy of subjective adherence measures using electronic monitoring (EM) as the reference standard is yet to be determined. This study aimed to evaluate correlates of TKI NA using EM and test the diagnostic accuracy of subjective adherence measures. PATIENTS AND METHODS: CML patients receiving a TKI for any duration were enrolled at 4 hematology institutes, and adherence was measured for 4 months. EM adherence was the reference adherence measure, expressed as the percentage of days with the drug taken as prescribed. Subjective adherence was measured using the Basel Assessment of Adherence to Immunosuppressive Medications Scale (BAASIS) self-report and clinician-reported visual analog scale (VAS) at 2 time points. Baseline theory-derived correlates of NA were identified using single and multiple regression analysis. The diagnostic accuracy of BAASIS and clinician-reported VAS was tested against an exploratory EM NA cutoff of < 95%. RESULTS: The median EM adherence (n = 55) was 97.5% (range, 48-100%), while the 25th percentile was 92.1%. Lack of membership in a CML patient support group, living alone, and third-line treatment were associated with EM NA on multiple regression analysis. The BAASIS self-report (n = 94) had a sensitivity of 67% and a specificity of 71% for diagnosing NA, while clinician-reported VAS (n = 89) had a sensitivity of 78% and specificity of 42%. CONCLUSION: A quarter of patients had potentially clinically meaningful NA. These NA correlates and the BAASIS provide a basis for identifying nonadherent patients who can be targeted by interventions.

Effect of Adherence-enhancing Interventions on Adherence to Tyrosine Kinase Inhibitor Treatment in Chronic Myeloid Leukemia (TAKE-IT): A Quasi-experimental Pre-Post Intervention Multicenter Pilot Study.

BACKGROUND: Nonadherence to tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia (CML) has been associated with inferior outcomes. Scarce evidence exists on the effectiveness of adherence-enhancing interventions. The present pilot study evaluated the feasibility and effectiveness of an intervention to improve TKI adherence in adult CML patients. PATIENTS AND METHODS: Using a quasi-experimental pre-post intervention design, we included a convenience sample of 58 CML patients (median age, 60.5 years; interquartile range, 19) receiving TKI treatment in 4 hematology institutes in Israel (median previous treatment duration, 34 months; interquartile range, 60). Of the 58 patients, 36 (62%) were receiving first-line treatment. TKI adherence was assessed using electronic monitoring for 7 months (4 months for the baseline assessment and for 3 months after the intervention) and defined as the percentage of days with dosing taken as prescribed. The multilevel intervention combined training of health care workers and multiple behavioral change techniques (eg, motivational interviewing, feedback on electronic monitoring printouts, behavioral change techniques tailored to reasons for nonadherence). The baseline and postintervention adherence were compared using generalized estimating equation models. RESULTS: The median baseline electronically monitored adherence (n = 55) was 97.5% (range, 48%-100%). The odds of taking the drug daily as prescribed were 58% greater after intervention (odds ratio, 1.58; 95% confidence interval [CI], 1.16-2.15). Adherence improved by only 1.5% overall (95% CI, 0.1%-2.8%) but by 8.5% (i.e. from 71.2% average adherence before intervention, to 79.6% after; P = .04) in a subgroup of 10 nonadherent patients (baseline adherence < 90%). CONCLUSION: TKI adherence improved with our pilot intervention, mainly in patients with suboptimal baseline adherence.

Integrative Oncology in Supportive Cancer Care in Israel.

PURPOSE: Integrative oncology (IO) services provide complementary/integrative medicine (CIM) therapies to patients as part of their supportive cancer care. In this study, we examine and compare the structural, operational, financial and academic/research-related aspects of IO services in Israeli oncology centers. METHODS: The medical directors of seven Israeli IO programs completed questionnaires which explored the objectives and organizational features of their service within the context of supportive cancer care. RESULTS: All participating IO services addressed patient-reported concerns related to quality of life and function, within the context of conventional supportive cancer care. The centers shared similar characteristics regarding the procedure of referral to their service and emphasized research and teaching initiatives within an academic framework, as part of their clinical practice. A number of obstacles to integration were identified, primarily those related to financial considerations, such as the need for patients to carry the cost of the CIM treatments. CONCLUSIONS: IO services situated within conventional oncology departments in Israel share a number of characteristics, as well as obstacles to their incorporation into standard care. All participating centers described both clinical and academic activities, including research initiatives and the promotion of CIM in an academic setting. Further research is needed in order to better understand the place of CIM in the oncology setting and prioritize the allocation of resources in order to advance the inclusion of CIM in standard supportive cancer care.

[Do's and don'ts in the establishment of an integrative medicine service in the public health care system--challenges and insights].

Although gratifying, it is somewhat misleading to describe the progress made in recent years in the field of integrative medicine just by counting the number of new programs established. This count, albeit ever-increasing, represents only one facet of the complex challenge that should concern us all--the development of a better healthcare system. In the real field, other rules apply. It is not sufficient for new integrative medicine services to survive or even to thrive if this is done in parallel to, or worse off in disconnect from, conventional medicine. The two systems, complementary and alternative medicine (CAM) and allopathic medicine, must collaborate in harmony for the sake of synergy. In order for that to happen, careful prior planning that addresses the multiple interests of the various stakeholders is warranted. This paper describes five key challenges and insights [institutional acceptance, Leadership support, the day after, the human factor, and program evaluation) gained from establishing an integrative oncology section within a tertiary academic medical center in Israel. It includes practical advice and useful tips in the form of do's and don'ts with the hope that these pearls would help others to estabLish and develop their own integrative medicine programs within the unique context of their hospitals and healthcare systems.

[Traditional immunosuppression--Lei Gong Teng in modern medicine].

Although the origin of many common modern medicines that are routinely being used nowadays in healthcare is in medicinal plants and fungi, herbal medicine as a standalone profession is no longer included in the curricula of most Western medical schools. The medicinal plant Lei Gong Teng [also known as Thunder God Vine, Tripterygium Wilfordii Hook f., that is core to traditional Chinese herbal medicine, was praised for its possible anti-inflammatory properties in ancient traditional scripts that date back thousands of years. Yet, modern interest in its proven immune-modulatory properties serves as a vivid example to the bridge that is being built, gradually but constantly, between the tradition of healing arts and the world of modern therapeutics. In this review we summarize the main findings from an increasing number of clinical and laboratory studies published in top peer-reviewed medical journals that verify the traditional indications for which Lei Gong Teng was used medicinally. Based on these findings, and the risk-benefit profile of the plant's debarked root, we conclude that Lei Gong Teng and its active metabolites should be included in the Israeli herbal pharmacopeia.

Evaluating intense rehabilitative therapies with and without acupuncture for children with cerebral palsy: a randomized controlled trial.

OBJECTIVE: To compare the outcomes of conventional therapies (physical, occupational, and hydrotherapies) plus acupuncture with those without acupuncture when administered intensely in the management of children with spastic cerebral palsy (CP). DESIGN: Evaluation-blind, prospective randomized controlled trial. SETTING: Therapies and video-recorded assessments at a children's hospital in Beijing, China, and blind scoring and data analyses at a university in the United States. PARTICIPANTS: Children (N=75), 12 to 72 months of age, with spastic CP. INTERVENTIONS: Intensely administered (5 times per week for 12wk) physical therapy, occupational therapy, and hydrotherapy either with acupuncture (group 1) or without acupuncture (group 2). To satisfy standard of care, group 2 subsequently received acupuncture (weeks 16-28). MAIN OUTCOME MEASURES: The Gross Motor Function Measure (GMFM)-66 and the Pediatric Evaluation of Disability Inventory (PEDI) assessments at 0, 4, 8, 12, 16, and 28 weeks. RESULTS: At the end of 12 weeks, there was no statistically significant difference between the 2 groups, but when group 2 received acupuncture (16-28wk) there was a shift toward improvement in the GMFM-66 and the PEDI-Functional Skills Self-Care and Mobility domain. When groups were combined, statistically significant improvements after intense therapies occurred from baseline to 12 weeks for each outcome measure at each Gross Motor Function Classification System (GMFCS) level. After adjusting for expected normative maturational gains based on age, the GMFM gains for children with GMFCS II level was statistically significant (P<.05) with a mean gain of 6.5 versus a predicted gain of 3.4. CONCLUSIONS: Intense early administered rehabilitation improves function in children with spastic CP. The contribution from acupuncture was unclear. Children's response varied widely, suggesting the importance of defining clinical profiles that identify which children might benefit most. Further research should explore how this approach might apply in the U.S.

Participatory medicine and patient empowerment towards personalized healthcare in multiple sclerosis.

The current understanding that the key for successful healthcare is an integrated approach, involving predictive, preventive, personalized and participatory medicine, is leading major changes. These are: a shift from medical decisions based on 'trial and error' to informed therapeutics based on diagnostics (theranostics); a shift from a 'disease-centered' to a 'patient-centered' approach; and a shift from a 'reactive' to 'proactive' medical approach. It is essential that not only the physician, but also the patient, becomes proactive. Therefore, beyond the integration of genomic medicine and predictive biomarkers into practice, patient empowerment and participatory medicine are gaining increasing attention. This requires, besides appropriate sharing of information between patients and healthcare providers, new insights in patient involvement, such as patient-reported outcomes, both at the clinical trial stage of drug development and during post-marketing follow-up assessments. Patient empowerment and participatory medicine, as part of predictive, preventive, personalized and participatory medicine, are especially crucial in paving the way towards optimized healthcare in complex and chronic neurological diseases, such as multiple sclerosis.

Informed consent in complementary and alternative medicine.

The objective of this study was to examine complementary and alternative medicine (CAM) practitioners' (i) attitudes toward informed consent and (ii) to assess whether standards of practice exist with respect to informed consent, and what these standards look like. The design and setting of the study constituted face-to-face qualitative interviews with 28 non-MD, community-based providers representing 11 different CAM therapeutic modalities. It was found that there is great deal of variability with respect to the informed consent process in CAM across providers and modalities. No unique profession-based patterns were identified. The content analysis yielded five major categories related to (i) general attitude towards the informed consent process, (ii) type and amount of information exchange during that process, (iii) disclosure of risks, (iv) discussions of alternatives, and (v) potential benefits. There is a widespread lack of standards with respect to the practice of informed consent across a broad range of CAM modalities. Addressing this problem requires concerted and systematic educational, ethical and judicial remedial actions. Informed consent, which is often viewed as a pervasive obligation is medicine, must be reshaped to have therapeutic value. Acknowledging current conceptions and misconception surrounding the practice of informed consent may help to bring about this change. More translational research is needed to guide this process.

Functional magnetic resonance imaging activation of the brain in children: real acupoint versus sham acupoint.

The purpose was to examine the brain activation patterns with acupuncture using real acupoint (Liv3) versus sham acupoint in healthy, sedated children using functional magnetic resonance imaging (fMRI). Functional magnetic resonance imaging scans of the brain for 10 healthy, sedated children were taken during stimulation of real acupoint (Liv3 [Taichong]) and a nearby sham acupoint in a randomized order, employing twisting and nontwisting methods using a blocked paradigm using a 2.0-T scanner. The functional data were analyzed by using SPM 99. Various regions of the brain were activated in 2 acupoints. However, the pattern was different for the 2 acupoints. We suggest specific cerebral activation patterns with acupuncture might explain some of its therapeutic effect.

When science meets medical tradition: what is needed for a dialogue on integrative medicine?

It has been more than a decade since the release of the National Institutes of Health (NIH) and Food and Drug Administration (FDA) consensus statement declaring that acupuncture is not an experimental therapy but a sound medical technique comparable in effectiveness to common conventional medical treatments for certain clinical conditions, such as nausea and pain. For the first time in the history of modern medicine, a traditional medical system gained legitimacy in the Western medical establishment. Yet, it remains unclear whether the motivation behind this endorsement represents a unity of conceptualization regarding the desired structure of the health care system and the nature of the integration of conventional and complementary and alternative medicine (CAM). Two (2) doctors, each representing a different paradigm, met in order to discuss and elucidate issues that relate to the nature of the proposed integration between allopathy and CAM. Their responses to key questions prompted by the 1997 NIH/FDA consensus statement create a platform for a unified "contract" that represents their vision regarding the essence of collaboration between the two systems of medicine. Based on the richness of their discussion, it is recommended that other medical centers engage in similar dialogues in order to establish their own contracts. It is hoped that this will pave the way toward mutual acceptance, both conceptually and strategically, of a pluralistic health care system.

Risk factors for arterial ischemic and hemorrhagic stroke in childhood.

This study assessed potential etiologies of arterial ischemic stroke and hemorrhagic stroke among children of Mainland China. From January 1996-June 2006, 251 patients with consecutive childhood stroke (aged 1 month through 16 years) were admitted to Beijing Children's Hospital. Arterial ischemic stroke accounted for the majority of cases (62.5%). Idiopathic stroke (32.5%) was more common than cardiac stroke (8.9%), vascular or arteriopathic stroke (21.0%), hematologic disorder-associated stroke (10.8%), and other etiologies (26.8%). Vitamin K deficiency was a major etiology in 72 of 94 hemorrhagic strokes (76.6%), most of which occurred in breastfeeding infants (80.6%) and those who received no vitamin K after birth (73.6%). Arteriovenous malformation (6.4%) was a frequent etiology in the remaining hemorrhagic stroke cases. We found that ischemic stroke in children is more common than hemorrhagic stroke, and many cases of ischemic stroke are idiopathic. Vitamin K deficiency was a major etiology in these young infants who experienced hemorrhagic stroke.

Randomized controlled trial of traditional Chinese medicine (acupuncture and tuina) in cerebral palsy: part 1--any increase in seizure in integrated acupuncture and rehabilitation group versus rehabilitation group?

OBJECTIVE: The objective of this study was to observe for any change in baseline seizure frequency with acupuncture in children with cerebral palsy. METHODS: A randomized controlled study was conducted: Group I consisted of integrated acupuncture, tuina, and rehabilitation (physiotherapy, occupational therapy, and hydrotherapy) for 12 weeks; and Group II consisted of rehabilitation (physiotherapy, occupational therapy, and hydrotherapy) for 12 weeks. After a washout period of 4 weeks, Group II then received acupuncture and tuina for 12 weeks. Each subject received 5 daily acupuncture sessions per week for 12 weeks (total = 60 sessions). All children were assessed for any change in seizure frequency during treatment. RESULTS: One hundred and sixteen (116) children were recruited and randomized into Group I (N = 58) and Group II (N = 58). Thirty-three (33) children withdrew (9 from Group I and 24 from Group II). Of the remaining 83 children, Group I consisted of 49 and Group II of 34 children. For baseline, 5 children (6%; 5/83) had seizures. During phase 1 (12 weeks) of integrative treatment and subsequent 4-week follow-up, 3 children in Group I had seizures. Among those 3 children with seizures, 1 child with prior history of recurrent febrile seizure had 3 more recurrent febrile seizures during acupuncture treatment and 2 children without any prior history of seizures had new-onset seizures (1 with 3 recurrent febrile seizures and 1 with afebrile seizure). For Group I, 2 children with epilepsy had no increase in seizure frequency during acupuncture treatment. For Group II during the phase 2 acupuncture period, none had increase in seizure frequency. In both groups, 4 of 5 children (80%; 2 in Group I and 2 in Group II) with seizures had no increase in seizure frequency during acupuncture treatment and follow-up. CONCLUSIONS: The risk of increasing seizure is not increased with acupuncture treatment for cerebral palsy.

Effect of acupuncture on the brain in children with spastic cerebral palsy using functional neuroimaging (FMRI).

We study the effect of acupuncture on brain activation patterns in children with cerebral palsy using functional magnetic resonance imaging (fMRI). fMRI of the whole brain was performed in 11 children with cerebral palsy and 10 healthy children during stimulation of a common acupoint in Traditional Medicine [Liv3 (Taichong)] on the left foot. We use both twisting and nontwisting methods with a blocked paradigm on a 2.0 Tesla MRI scanner. Functional data were analyzed by using Statistical Parametric Mapping software (SPM 99). Both signal increase and decrease in various regions of the brain were found in both groups of children. However, the pattern was different for the 2 groups, especially with decreases in signal regions. We suggest that the observed differences between children with cerebral palsy and healthy children with the stimulation of acupoint Liv3 might be due to blockage of the liver meridian in children with cerebral palsy.

[Touching cancer: shiatsu as complementary treatment to support cancer patients].

In recent years there has been an increase in the interest of cancer patients in receiving complementary medicine therapies as supportive measures to cure the disease. In response, medical units that combine conventional and complementary medicine (integrative medicine) have been established in leading cancer centers worldwide. In Israel, a special integrative medicine unit that combines mind-body, Chinese medicine, nutrition, herbs, supplements, and manual therapies (such as shiatsu) before, during and after conventional anti-cancer therapies has been established as an integral part of the Davidoff Comprehensive Cancer Center in 2006. Shiatsu represents a group of manual therapeutic techniques, including acupressure. Shiatsu offers cancer patients a non-pharmacologic method to relieve symptoms and improve quality of life throughout the course of illness. Research indicates that acupressure is relatively effective and safe for common cancer-related symptoms such as nausea, vomiting and insomnia. In our experience, shiatsu is also relatively effective and safe for other common symptoms such as fatigue, muscular pain and body image dissatisfaction. Yet, insufficient evidence exists to delineate the best means by which shiatsu and other manual therapies could or should be integrated into routine cancer care. The purpose of the present paper is to describe what is currently known about this topic in order to support decision-making that is based on facts, rather than on myths and misconceptions. We call for more research that examines the effectiveness and safety of shiatsu and other manual therapies in the care of cancer patients.

Potential synergism between hypnosis and acupuncture­is the whole more than the sum of its parts?

Both hypnosis and acupuncture have gained credibility over the years in their effectiveness for treating various health conditions. Currently, each of these treatments is administered in distinct settings and separate times. That is, even if patients receive both treatments as part of a multidimensional therapeutic program, they would typically receive them separately rather than simultaneously at the same session. This separation however might be undesirable since, at least theoretically, hypnosis and acupuncture could potentially augment each other if administered concomitantly. In this article we outline the rationale for this hypothesis and discuss the potential ramifications of its implementation.

Patients' experiences and perceptions of a consultative model integrative medicine clinic: a qualitative study.

OBJECTIVE: A common theme in integrative medicine (IM) is patient-centered partnering in care between patients and providers. Despite the stated ideals, few studies have assessed patients' perspectives on their actual experience in the context of a specific care model. The purpose of the present study was to retrospectively explore and compare experiences of cancer and noncancer patients under care in a consultative IM outpatient teaching clinic in the south-western United States. DESIGN: Qualitative study using inductive content analysis of focus group interview transcripts (2 groups of adult patients with cancers of various types and 1 group of chronically ill noncancer patients with mixed diagnoses). METHOD: Participants were recruited by random selection from a pool of eligible patients. Groups were conducted with patients who had completed their initial conventional cancer treatment and were at least 6 months postconsultation with an IM clinic physician. Transcripts of the audiotaped focus groups were analyzed. RESULTS: Cancer patients (n = 15) and noncancer patients (n = 6) (mean age, 60 years; 77% women) expressed overall satisfaction with IM, emphasizing (1) expansion of treatment options with lower perceived toxicity than conventional therapies, (2) positive experiences of the IM physician as caring and taking time to listen, and (3) improved self-care skills and sense of empowerment. Cancer patients noted positive relationships with their conventional MDs more than did noncancer patients, although both groups appreciated the IM physicians' communication styles. CONCLUSION: Patients experience a consultative integrative clinic model overall as favorable. The impact on outcomes, costs, and long-term quality of life requires additional study.