The Complexity of the Homeopathic Healing Response Part 1: The Role of the Body as a Complex Adaptive System in Simillimum-Initiated Recovery from Disease.

BACKGROUND: The concepts of complex systems science enhance the understanding of how people develop and recover from disease. Living systems (human beings, animals, and plants) are self-organizing complex adaptive systems (CAS): that is, interconnected networks. CAS maintain life by initiating and carrying out non-linear dynamical changes to optimize survival fitness and function in the context of an ever-changing environment. AIMS: In Part 1 of this two-part paper, we relate concepts from complex systems science to homeopathic healing. The systemic changes of homeopathic healing involve adaptive patterns of responses to salient signals (similia) for reversing disease patterns and generating emergent multi-symptom healing over time. METHODS AND RESULTS: This narrative review relates homeopathic clinical practice theory to complex systems and network research. Homeopathic medicines communicate individually salient environmental information to the organism, with effects that are multi-system and indirect. The body's defense mechanisms recognize the self-similar information that the correctly chosen simillimum medicine at low dose conveys as a weak external/internal environmental stressor or danger signal (hormetin) to mobilize neural and cellular defenses. The body networks then use endogenous cell to cell signaling and amplify the small magnitude signal information. The results are disproportionately large: that is, non-linear, adaptive, modifications across the inter-connected self-organized biological networks/sub-systems of the body. CAS amplification mechanisms for small or weak signals include stochastic resonance, time-dependent sensitization, and hormesis. CONCLUSIONS: The body as a complex system has the capacity for self-organization, emergence and self-similarity over global (overall health and wellbeing) and local (organ) levels of organization. These features are key for future research on the systemic healing that evolves over time during individualized homeopathic treatment.

The Complexity of the Homeopathic Healing Response Part 2: The Role of the Homeopathic Simillimum as a Complex System in Initiating Recovery from Disease.

BACKGROUND: Evidence indicates that homeopathic medicines are complex self-organizing nano-scale systems that generate unique low-intensity electromagnetic signals and/or quantum coherence domains. In Part 1, we reviewed relevant concepts from complex adaptive systems science on living systems for the nature of homeopathic healing. AIM: In Part 2, we discuss the complex-system nature of homeopathic medicines. The aim is to relate the evidence on the nature and properties of homeopathic medicines to the complex systems model for homeopathic healing. METHODS AND RESULTS: The work is a narrative review, with complexity model development for the nature of homeopathic medicines. Studies suggest that homeopathic manufacturing generates nano-structures of source material, silica and silicon quantum dots if succussed in glassware or including botanical source materials; or carbon quantum dots if succussed in plastic or including any organic source materials, as well as solute-induced water nano-structures carrying medicine-specific information. On contact with physiological fluids (e.g., blood plasma), there is evidence that nano-structures additionally adsorb individualized patterns of the recipient's own proteins on to their surfaces to create a unique protein corona coat (shell). Thus, the simillimum may generate a personalized biological identity upon administration. Consequently, a medicine can serve as an individually salient, self-similar information carrier, whose protein corona constituent pattern reflects the individual's current internal state of health/disease. Homeopathic medicine complexity emerges from interactions of the component parts from source, silica from glassware or carbon from plastic containers, solvents (lactose, water, ethanol), adsorbed biomolecule layers from plant or animal sources, and adsorbed biomolecules of the recipient. Low doses of these complex medicines can act as biological signaling agents to initiate hormesis via a network-wide pattern of adaptive responses by the recipient complex adaptive system, rather than as conventional pharmaceutical drugs. Biological mediators of adaptive responses include inter-connected network elements of the cell danger/damage defense system: for example, gene expression, reactive oxygen species, heat shock proteins, cytokines, macrophages, T-cells, and associated brain-immune system mediator pathways. CONCLUSIONS: Every homeopathic medicine is a complex nano-scale system involving multiple inter-connected, interacting components, and emergent properties. Simillimum individualization derives from formation of a unique personalized protein corona shell adsorbed to the reactive surface of the homeopathic nano-structures on contact with the recipient's body fluids. Low doses of such complex nano-structures initiate the adaptive processes of hormesis to mobilize endogenous healing of a disease state. The capacity for self-organization and self-similarity in complex systems is the key to future research on the nature of homeopathic medicines and systemic healing during individualized homeopathic treatment.

Low Doses of Traditional Nanophytomedicines for Clinical Treatment: Manufacturing Processes and Nonlinear Response Patterns.

The purpose of the present paper is to (a) summarize evidence for the nanoparticle nature and biological effects of traditional homeopathically-prepared medicines at low and ultralow doses; (b) provide details of historically-based homeopathic green manufacturing materials and methods, relating them to top-down mechanical attrition and plant-based biosynthetic processes in modern nanotechnology; (c) outline the potential roles of nonlinear dose-responses and dynamical interactions with complex adaptive systems in generating endogenous amplification processes during low dose treatment. Possible mechanisms of low dose effects, for which there is evidence involving nanoparticles and/or homeopathically-manufactured medicines, include hormesis, time-dependent sensitization, and stochastic resonance. All of the proposed mechanisms depend upon endogenous nonlinear amplification processes in the recipient organism in interaction with the salient, albeit weak signal properties of the medicine. Conventional ligand-receptor mechanisms relevant to higher doses are less likely involved. Effects, especially for homeopathically-prepared nanophytomedicines, include bidirectional host state-dependent changes in function. Homeopathic clinicians report successful treatment of serious infections and cancers. Preclinical biological evidence is consistent with such claims. Controlled biological data on homeopathically-prepared medicines indicate modulation of gene expression and biological signaling pathways regulating cell cycles, immune reactions, and central nervous system function from studies on cells, animals, and human subjects. As a 200-year old system of traditional medicine used by millions of people worldwide, homeopathy offers a pulsed low dose treatment strategy and strong safety record to facilitate progress in translational nanomedicine with plants and other natural products. In turn, modern nanotechnology methods can improve homeopathic manufacturing procedures, characterize nanoparticle end-products, and describe interactions of homeopathic nanophytomedicines with living systems at the nanoparticle and even individual organism level of detection. Faster progress toward safe and effective personalized nanophytomedicine treatments can result.

Enhancement of adaptive biological effects by nanotechnology preparation methods in homeopathic medicines.

Multiple studies have demonstrated that traditional homeopathic manufacturing reagents and processes can generate remedy source and silica nanoparticles (NPs). Homeopathically-made NPs would initiate adaptive changes in an organism as a complex adaptive system (CAS) or network. Adaptive changes would emerge from several different endogenous amplification processes that respond to exogenous danger or threat signals that manufactured nanomaterials convey, including (1) stochastic resonance (SR) in sensory neural systems and (2) time-dependent sensitization (TDS)/oscillation. SR is nonlinear coherent amplification of a weak signal by the superposition of a larger magnitude white noise containing within it the same frequencies of the weak signal. TDS is progressive response magnitude amplification and oscillatory reversal in response direction to a given low dose at physiological limits with the passage of time. Hormesis is an overarching adaptive phenomenon that reflects the observed nonlinear adaptive dose-response relationship. Remedies would act as enhanced micro- and nanoscale forms of their source material via direct local ligand-receptor interactions at very low potencies and/or by triggering systemic adaptive network dynamical effects via their NP-based electromagnetic, optical, and quantum mechanical properties at higher potencies. Manufacturing parameters including dilution modify sizes, shapes, and surface charges of nanoparticles, thereby causing differences in physico-chemical properties and biological effects. Based on surface area, size, shape, and charge, nanoparticles adsorb a complex pattern of serum proteins, forming a protein corona on contact that constitutes a unique biological identity. The protein corona may capture individualized dysfunctional biological mediator information of the organism onto the surfaces of the salient, i.e., resonant, remedy nanostructures. SR would amplify this weak signal from the salient remedy NPs with protein corona adsorbed, leading to sensitized nonlinear dynamical modulation of gene expression and associated changes in biological signaling pathways. When the system reaches its physiological limits during a homeopathic aggravation or the natural disease state, the amplified remedy signal triggers a nonlinear reversal in dynamical direction back towards health.

Acute electroencephalographic effects from repeated olfactory administration of homeopathic remedies in individuals with self-reported chemical sensitivity.

BACKGROUND: Homeopaths report that individuals with heightened self-reported environmental chemical intolerance (CI) exhibit increased reactivity to homeopathic remedies. Persons high in CI sensitize their electroencephalographic (EEG) alpha responses to repeated intermittent chemical exposures. PRIMARY STUDY OBJECTIVE: The present feasibility study explored interactions between CI and one of two specific homeopathic remedies over time (Sulphur or Pulsatilla nigricans [Pulsatilla]). DESIGN: This study used a two-arm, double-blind, placebo-controlled repeated measures design. Intervention Participants underwent a series of three once-weekly sessions during which they repeatedly sniffed one remedy (6c, 12c, 30c; one potency per week) matched to their Homeopathic Constitutional Type Questionnaire (CTQ) type and two solvent controls (distilled water and a waterethanol [95%] solution). Within sessions, remedies and control solvents were administered via 2-second sniffs (eight sniffs of each of four different succussion levels per potency, in randomized order). PARTICIPANTS: Participants were college student volunteers (N = 96, ages 18-30, both sexes), screened for good health and relatively elevated Sulphur or Pulsatilla symptom pattern scores on the Homeopathic Constitutional Type Questionnaire (CTQ). Participants also completed a validated trait CI scale. PRIMARY OUTCOME MEASURES: Average 19-lead relative EEG alpha power (alpha 1 8-10 Hz; alpha 2 10-12 Hz). RESULTS: Trait CI interacted significantly with time factors for each remedy (both over visit weeks and over sniff cycles during sessions). The patterns were nonlinear and differed between the two remedies. Individuals high in CI showed greater variability over time in remedy EEG alpha effects than did those low in CI. CONCLUSION: The data suggest that CI, with an underlying susceptibility to time-dependent sensitization and oscillatory responses, could contribute to nonlinear dose-response patterns and inconsistent reproducibility of homeopathic clinical care and research.

Testing the nanoparticle-allostatic cross-adaptation-sensitization model for homeopathic remedy effects.

Key concepts of the Nanoparticle-Allostatic Cross-Adaptation-Sensitization (NPCAS) Model for the action of homeopathic remedies in living systems include source nanoparticles as low level environmental stressors, heterotypic hormesis, cross-adaptation, allostasis (stress response network), time-dependent sensitization with endogenous amplification and bidirectional change, and self-organizing complex adaptive systems. The model accommodates the requirement for measurable physical agents in the remedy (source nanoparticles and/or source adsorbed to silica nanoparticles). Hormetic adaptive responses in the organism, triggered by nanoparticles; bipolar, metaplastic change, dependent on the history of the organism. Clinical matching of the patient's symptom picture, including modalities, to the symptom pattern that the source material can cause (cross-adaptation and cross-sensitization). Evidence for nanoparticle-related quantum macro-entanglement in homeopathic pathogenetic trials. This paper examines research implications of the model, discussing the following hypotheses: Variability in nanoparticle size, morphology, and aggregation affects remedy properties and reproducibility of findings. Homeopathic remedies modulate adaptive allostatic responses, with multiple dynamic short- and long-term effects. Simillimum remedy nanoparticles, as novel mild stressors corresponding to the organism's dysfunction initiate time-dependent cross-sensitization, reversing the direction of dysfunctional reactivity to environmental stressors. The NPCAS model suggests a way forward for systematic research on homeopathy. The central proposition is that homeopathic treatment is a form of nanomedicine acting by modulation of endogenous adaptation and metaplastic amplification processes in the organism to enhance long-term systemic resilience and health.

Chemical intolerance in primary care settings: prevalence, comorbidity, and outcomes.

PURPOSE: This study extends previous community-based studies on the prevalence and clinical characteristics of chemical intolerance in a sample of primary care clinic patients. We evaluated comorbid medical and psychiatric disorders, functional status, and rates of health care use. METHODS: A total of 400 patients were recruited from 2 family medicine clinic waiting rooms in San Antonio, Texas. Patients completed the validated Quick Environmental Exposure and Sensitivity Inventory (QEESI) to assess chemical intolerance; the Primary Care Evaluation of Mental Disorders (PRIME-MD) screen for possible psychiatric disorders; the Dartmouth-Northern New England Primary Care Cooperative Information Project (Dartmouth COOP) charts for functional status; and the Healthcare Utilization Questionnaire. RESULTS: Overall, 20.3% of the sample met criteria for chemical intolerance. The chemically intolerant group reported significantly higher rates of comorbid allergies and more often met screening criteria for possible major depressive disorder, panic disorder, generalized anxiety disorder, and alcohol abuse disorder, as well as somatization disorder. The total number of possible mental disorders was correlated with chemical intolerance scores (P <.001). Controlling for demographics, patients with chemical intolerance were significantly more likely to have poorer functional status, with trends toward increased medical service use when compared with non-chemically intolerant patients. After controlling for comorbid psychiatric conditions, the groups differed significantly only regarding limitations of social activities. CONCLUSIONS: Chemical intolerance occurs in 1 of 5 primary care patients yet is rarely diagnosed by busy practitioners. Psychiatric comorbidities contribute to functional limitations and increased health care use. Chemical intolerance offers an etiologic explanation. Symptoms may resolve or improve with the avoidance of salient chemical, dietary (including caffeine and alcohol), and drug triggers. Given greater medication intolerances in chemical intolerance, primary care clinicians could use the QEESI to identify patients for appropriate triage to comprehensive nonpharmacologic care.

A model for homeopathic remedy effects: low dose nanoparticles, allostatic cross-adaptation, and time-dependent sensitization in a complex adaptive system.

BACKGROUND: This paper proposes a novel model for homeopathic remedy action on living systems. Research indicates that homeopathic remedies (a) contain measurable source and silica nanoparticles heterogeneously dispersed in colloidal solution; (b) act by modulating biological function of the allostatic stress response network (c) evoke biphasic actions on living systems via organism-dependent adaptive and endogenously amplified effects; (d) improve systemic resilience. DISCUSSION: The proposed active components of homeopathic remedies are nanoparticles of source substance in water-based colloidal solution, not bulk-form drugs. Nanoparticles have unique biological and physico-chemical properties, including increased catalytic reactivity, protein and DNA adsorption, bioavailability, dose-sparing, electromagnetic, and quantum effects different from bulk-form materials. Trituration and/or liquid succussions during classical remedy preparation create "top-down" nanostructures. Plants can biosynthesize remedy-templated silica nanostructures. Nanoparticles stimulate hormesis, a beneficial low-dose adaptive response. Homeopathic remedies prescribed in low doses spaced intermittently over time act as biological signals that stimulate the organism's allostatic biological stress response network, evoking nonlinear modulatory, self-organizing change. Potential mechanisms include time-dependent sensitization (TDS), a type of adaptive plasticity/metaplasticity involving progressive amplification of host responses, which reverse direction and oscillate at physiological limits. To mobilize hormesis and TDS, the remedy must be appraised as a salient, but low level, novel threat, stressor, or homeostatic disruption for the whole organism. Silica nanoparticles adsorb remedy source and amplify effects. Properly-timed remedy dosing elicits disease-primed compensatory reversal in direction of maladaptive dynamics of the allostatic network, thus promoting resilience and recovery from disease. SUMMARY: Homeopathic remedies are proposed as source nanoparticles that mobilize hormesis and time-dependent sensitization via non-pharmacological effects on specific biological adaptive and amplification mechanisms. The nanoparticle nature of remedies would distinguish them from conventional bulk drugs in structure, morphology, and functional properties. Outcomes would depend upon the ability of the organism to respond to the remedy as a novel stressor or heterotypic biological threat, initiating reversals of cumulative, cross-adapted biological maladaptations underlying disease in the allostatic stress response network. Systemic resilience would improve. This model provides a foundation for theory-driven research on the role of nanomaterials in living systems, mechanisms of homeopathic remedy actions and translational uses in nanomedicine.

Nonlinear dynamical systems effects of homeopathic remedies on multiscale entropy and correlation dimension of slow wave sleep EEG in young adults with histories of coffee-induced insomnia.

BACKGROUND: Investigators of homeopathy have proposed that nonlinear dynamical systems (NDS) and complex systems science offer conceptual and analytic tools for evaluating homeopathic remedy effects. Previous animal studies demonstrate that homeopathic medicines alter delta electroencephalographic (EEG) slow wave sleep. The present study extended findings of remedy-related sleep stage alterations in human subjects by testing the feasibility of using two different NDS analytic approaches to assess remedy effects on human slow wave sleep EEG. METHODS: Subjects (N=54) were young adult male and female college students with a history of coffee-related insomnia who participated in a larger 4-week study of the polysomnographic effects of homeopathic medicines on home-based all-night sleep recordings. Subjects took one bedtime dose of a homeopathic remedy (Coffea cruda or Nux vomica 30c). We computed multiscale entropy (MSE) and the correlation dimension (Mekler-D2) for stages 3 and 4 slow wave sleep EEG sampled in artifact-free 2-min segments during the first two rapid-eye-movement (REM) cycles for remedy and post-remedy nights, controlling for placebo and post-placebo night effects. RESULTS: MSE results indicate significant, remedy-specific directional effects, especially later in the night (REM cycle 2) (CC: remedy night increases and post-remedy night decreases in MSE at multiple sites for both stages 3 and 4 in both REM cycles; NV: remedy night decreases and post-remedy night increases, mainly in stage 3 REM cycle 2 MSE). D2 analyses yielded more sporadic and inconsistent findings. CONCLUSIONS: Homeopathic medicines Coffea cruda and Nux vomica in 30c potencies alter short-term nonlinear dynamic parameters of slow wave sleep EEG in healthy young adults. MSE may provide a more sensitive NDS analytic method than D2 for evaluating homeopathic remedy effects on human sleep EEG patterns.

Developing a patient-centered outcome measure for complementary and alternative medicine therapies I: defining content and format.

BACKGROUND: Patients receiving complementary and alternative medicine (CAM) therapies often report shifts in well-being that go beyond resolution of the original presenting symptoms. We undertook a research program to develop and evaluate a patient-centered outcome measure to assess the multidimensional impacts of CAM therapies, utilizing a novel mixed methods approach that relied upon techniques from the fields of anthropology and psychometrics. This tool would have broad applicability, both for CAM practitioners to measure shifts in patients' states following treatments, and conventional clinical trial researchers needing validated outcome measures. The US Food and Drug Administration has highlighted the importance of valid and reliable measurement of patient-reported outcomes in the evaluation of conventional medical products. Here we describe Phase I of our research program, the iterative process of content identification, item development and refinement, and response format selection. Cognitive interviews and psychometric evaluation are reported separately. METHODS: From a database of patient interviews (n = 177) from six diverse CAM studies, 150 interviews were identified for secondary analysis in which individuals spontaneously discussed unexpected changes associated with CAM. Using ATLAS.ti, we identified common themes and language to inform questionnaire item content and wording. Respondents' language was often richly textured, but item development required a stripping down of language to extract essential meaning and minimize potential comprehension barriers across populations. Through an evocative card sort interview process, we identified those items most widely applicable and covering standard psychometric domains. We developed, pilot-tested, and refined the format, yielding a questionnaire for cognitive interviews and psychometric evaluation. RESULTS: The resulting questionnaire contained 18 items, in visual analog scale format, in which each line was anchored by the positive and negative extremes relevant to the experiential domain. Because of frequent informant allusions to response set shifts from before to after CAM therapies, we chose a retrospective pretest format. Items cover physical, emotional, cognitive, social, spiritual, and whole person domains. CONCLUSIONS: This paper reports the success of a novel approach to the development of outcome instruments, in which items are extracted from patients' words instead of being distilled from pre-existing theory. The resulting instrument, focused on measuring shifts in patients' perceptions of health and well-being along pre-specified axes, is undergoing continued testing, and is available for use by cooperating investigators.

Short-term effects of repeated olfactory administration of homeopathic sulphur or pulsatilla on electroencephalographic alpha power in healthy young adults.

INTRODUCTION: Homeopathic pathogenetic trials usually rely on symptom self report measures. Adding objective biomarkers could enhance detection of subtle initial remedy effects. The present feasibility study examined electroencephalographic (EEG) effects of repeated olfactory administration of two polycrest remedies. METHODS: College student volunteers (ages 18-30, both sexes) from an introductory psychology course were screened for good health and relatively elevated Sulphur or Pulsatilla symptom scores on the Homeopathic Constitutional Type Questionnaire (CTQ). Subjects underwent a series of 3 once-weekly double-blind sessions during which they repeatedly sniffed the remedy matched to their CTQ type and solvent controls. Each remedy was given in a 6c, 12c, and 30c potency, one potency per week, in randomly assigned order. Solvent controls included both plain distilled water and a water-ethanol (95%) solution. All sniff test solutions were further diluted just prior to laboratory sessions (0.5 ml test solution in 150 ml distilled water). Within a session, remedies and control solvents were administered via 2-s sniffs (8 sniffs of each of 4 different succussion levels for the potency in randomized order). Primary outcome variable was relative EEG power (alpha 1 8-10 Hz; alpha 2 10-12 Hz) averaged over 19 electrode sites, including all succussions for a given potency. RESULTS: Mixed-effect models revealed significant main effects for remedy type (Sulphur >Pulsatilla) in both alpha bands, controlling for gender, baseline resting EEG alpha, and solvent control responses. Additional analyses showed significant nonlinear interactions between dilution and time (weekly session) in alpha 2 for both remedies and alpha 1 for Sulphur. CONCLUSION: EEG alpha offers an objective biomarker of remedy effects for future studies and potential method for distinguishing time-dependent effects of specific remedies and remedy potencies from one another.

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.

The process of whole person healing: "unstuckness" and beyond.

OBJECTIVE: The purpose of the present study was to fully explore the descriptions of patients' experiences of change after receipt of whole systems of complementary and alternative medicine (CAM) treatment. The aim was to develop an understanding of "unstuckness," including characterization of states, processes, and modifying factors. DESIGN: This was a secondary descriptive qualitative analysis, using techniques borrowed from phenomenology and grounded theory. SETTING/LOCATION: Three existent datasets collected at two different universities in the United States and Canada were used in the secondary analysis. PARTICIPANTS: Patients with chronic illnesses (including cancer and multiple nonmalignant conditions) who were treated with different packages of care were interviewed for the primary three studies (n = 76 with over 150 interview sessions). Complete data sets from these participants were used in this secondary analysis. OUTCOME MEASURES/DATA COLLECTION TECHNIQUES: Original transcripts were coded asking specific research questions about the experience of change subsequent to whole systems treatments. RESULTS: Data clearly indicated experiential differences between stuckness, unsticking, and unstuckness. Descriptors and characteristics of each state were identified, as was an initial grounded theory of change or transformation that occurs as an outcome of whole medical systems of CAM. CONCLUSIONS: The results provide preliminary conceptualizations and descriptions of the impact that CAM whole systems interventions may have on the individual' s life courses. This constitutes a first step in the identification, measurement, and evaluation of whole systems outcomes in a clinical setting. The emerging conceptualization of the process from stuckness to transformation may also provide a link between clinical research and systems science theory.

Adjunctive care with nutritional, herbal, and homeopathic complementary and alternative medicine modalities in stroke treatment and rehabilitation.

This article presents an overview of nutritional, herbal, and homeopathic treatment options from complementary and alternative medicine (CAM) as adjuncts in stroke prevention, treatment, and rehabilitation. Despite many promising leads, the evidence does not favor recommendation of most of these treatments from a public health policy perspective. However, simple preventive interventions such as use of a high-quality multivitamin/multimineral supplement in patients with undernutrition may improve outcomes with minimal long-term risk. Natural agents such as the antioxidant alphalipoic acid, certain traditional Asian herbal mixtures, and some homeopathically prepared remedies show promise for reducing infarct size and associated impairments. A number of nutrients and herbs may assist in treatment of stroke-related complications such as pressure sores, urinary tract infections, and pneumonia. Individualized homeopathy may even play a helpful adjunctive role in treatment of sepsis. However, a great deal of systematic research effort lies ahead before most of the options discussed would meet mainstream medical standards for introduction into routine treatment regimens.

Models for the study of whole systems.

This article summarizes a network and complex systems science model for research on whole systems of complementary and alternative medicine (CAM) such as homeopathy and traditional Chinese medicine. The holistic concepts of networks and nonlinear dynamical complex systems are well matched to the global and interactive perspectives of whole systems of CAM, whereas the reductionistic science model is well matched to the isolated local organ, cell, and molecular mechanistic perspectives of pharmaceutically based biomedicine. Whole systems of CAM are not drugs with specific actions. The diagnostic and therapeutic approaches of whole systems of CAM produce effects that involve global and patterned shifts across multiple subsystems of the person as a whole. For homeopathy, several characteristics of complex systems, including the probabilistic nature of attractor patterns, variable sensitivity of complex systems to initial conditions, and emergent behaviors in the evolution of a system in its full environmental context over time, could help account for the mixed basic science and controlled clinical trial research findings, in contrast with the consistently positive outcomes of observational studies in the literature. Application of theories and methods from complex systems and network science can open a new era of advances in understanding factors that lead to good versus poor individual global outcome patterns and to rational triage of patients to one type of care over another. The growing reliance on complex systems thinking and systems biology for cancer research affords a unique opportunity to bridge between the CAM and conventional medical worlds with some common language and conceptual models.

Obstructive sleep apnea and ischemic heart disease in southwestern US veterans: implications for clinical practice.

This study describes associations between obstructive sleep apnea (OSA), intake of food rich in antioxidant nutrients, and ischemic heart disease (IHD) in military veterans. Subjects were male veterans (n=211), 54 to 85 years of age, and enrolled in primary care clinics at the Southern Arizona Veterans Affairs Health Care System (SAVAHCS), Tucson, AZ. Measures included the SAVAHCS Minority Vascular Center Questionnaire, the Sleep Heart Health Study Sleep Habits Questionnaire, the Arizona Food Frequency Questionnaire, height, weight, and blood pressure. Veterans with OSA were significantly more likely to be obese, to have elevated systolic blood pressure and physician-diagnosed IHD, more likely to undergo coronary angiography, and less likely to consume foods rich in cardioprotective antioxidants compared to veterans without OSA. After adjusting for confounding variables, the association between OSA and IHD remains significant [adjusted OR=2.99, confidence interval (CI)=1.07-8.42]. These data reinforce the importance of recognizing OSA within the veterans affairs health care system and suggest that early detection of OSA may improve veterans' health and well-being and reduce associated medical costs.

A profile of military veterans in the southwestern United States who use complementary and alternative medicine: implications for integrated care.

BACKGROUND: Complementary and alternative medicine (CAM) use and expenditures are on the rise in the United States. Although civilian users of CAM have been well described, little is known about military veteran users of CAM. OBJECTIVE: To describe military veteran CAM users in the southwestern United States. METHODS: The study population comprised 508 military veterans randomly selected from Southern Arizona Veterans Administration Health Care System (Tucson) primary care patient lists, who had agreed to participate in a telephone interview. The chi(2) test was used to analyze CAM use by demographic characteristics, military service, military-related health outcomes, and physician-diagnosed health complaints. Logistic regression was used to determine predictor variables. RESULTS: Of the 508 subjects, 252 (49.6%) reported CAM use. Military veteran CAM users were significantly more likely to be non-Hispanic white, earn more than $50 000 per year (both P<.05), and have greater than 12 years of education (P<.01). Current high daily stress, perceived negative impact of military life on physical or mental health, and physician-diagnosed chronic illnesses (eg, gastrointestinal problems, insomnia, and asthma) were statistically associated with CAM use. Regression analysis provided adjusted odds ratios and indicated that ethnicity (non-Hispanic white), higher education, greater current daily stress, and overseas military experience were significant predictors of CAM use by these veterans (each P<.05). CONCLUSIONS: Ethnicity, education, income, and several chronic health complaints are consistent with civilian CAM use. Findings also suggest, however, that physicians providing conventional medical care need to be aware of experiences unique to CAM-using military veterans.

Integrative medicine and systemic outcomes research: issues in the emergence of a new model for primary health care.

Clinicians and researchers are increasingly using the term integrative medicine to refer to the merging of complementary and alternative medicine (CAM) with conventional biomedicine. However, combination medicine (CAM added to conventional) is not integrative. Integrative medicine represents a higher-order system of systems of care that emphasizes wellness and healing of the entire person (bio-psycho-socio-spiritual dimensions) as primary goals, drawing on both conventional and CAM approaches in the context of a supportive and effective physician-patient relationship. Using the context of integrative medicine, this article outlines the relevance of complex systems theory as an approach to health outcomes research. In this view, health is an emergent property of the person as a complex living system. Within this conceptualization, the whole may exhibit properties that its separate parts do not possess. Thus, unlike biomedical research that typically examines parts of health care and parts of the individual, one at a time, but not the complete system, integrative outcomes research advocates the study of the whole. The whole system includes the patient-provider relationship, multiple conventional and CAM treatments, and the philosophical context of care as the intervention. The systemic outcomes encompass the simultaneous, interactive changes within the whole person.

JP-8 jet fuel exposure and divided attention test performance in 1991 Gulf War veterans.

INTRODUCTION: Previous research indicates that a large cohort of veterans from the 1991 Gulf War report polysymptomatic conditions. These syndromes often involve neurocognitive complaints, fatigue, and musculoskeletal symptoms, thus overlapping with civilian illnesses from low levels of environmental chemicals, chronic fatigue syndrome, and fibromyalgia. METHODS: To test for time-dependent changes over repeated intermittent exposures, we evaluated objective performance on a computerized visual divided attention test in chronically unhealthy Gulf War veterans (n = 22 ill with low-level chemical intolerance (CI); n = 24 ill without CI), healthy Gulf War veterans (n = 23), and healthy Gulf War era veterans (n = 20). Testing was done before and after each of three weekly, double blind, low-level JP-8 jet fuel or clean air sham exposure laboratory sessions, including acoustic startle stimuli. RESULTS: Unhealthy veterans receiving jet fuel had faster mean peripheral reaction times over sessions compared with unhealthy veterans receiving sham clean air exposures. Unhealthy Gulf veterans with CI exhibited faster post- vs. pre-session mean central reaction times compared with unhealthy Gulf veterans without CI. Findings were controlled for psychological distress variables. DISCUSSION: These data on unhealthy Gulf veterans show an acceleration of divided attention task performance over the course of repeated low-level JP-8 exposures. The present faster reaction times are consistent with rat neurobehavioral studies on environmental toxicant cross-sensitization and nonlinear dose-response patterns with stimulant drugs, as well as some previous civilian studies using other exposure agents. Together with previous research findings, the data suggest involvement of central nervous system dopaminergic pathways in affected Gulf veterans.

Patient-Provider Interactions Affect Symptoms in Gastroesophageal Reflux Disease: A Pilot Randomized, Double-Blind, Placebo-Controlled Trial.

BACKGROUND: It is unclear whether the benefits that some patients derive from complementary and integrative medicine (CIM) are related to the therapies recommended or to the consultation process as some CIM provider visits are more involved than conventional medical visits. Many patients with gastrointestinal conditions seek out CIM therapies, and prior work has demonstrated that the quality of the patient-provider interaction can improve health outcomes in irritable bowel syndrome, however, the impact of this interaction on gastroesophageal reflux disease (GERD) is unknown. We aimed to assess the safety and feasibility of conducting a 2 x 2 factorial design study preliminarily exploring the impact of the patient-provider interaction, and the effect of an over-the-counter homeopathic product, Acidil, on symptoms and health-related quality of life in subjects with GERD. METHODS: 24 subjects with GERD-related symptoms were randomized in a 2 x 2 factorial design to receive 1) either a standard visit based on an empathic conventional primary care evaluation or an expanded visit with questions modeled after a CIM consultation and 2) either Acidil or placebo for two weeks. Subjects completed a daily GERD symptom diary and additional measures of symptom severity and health-related quality of life. RESULTS: There was no significant difference in GERD symptom severity between the Acidil and placebo groups from baseline to follow-up (p = 0.41), however, subjects who received the expanded visit were significantly more likely to report a 50% or greater improvement in symptom severity compared to subjects who received the standard visit (p = 0.01). Total consultation length, perceived empathy, and baseline beliefs in CIM were not associated with treatment outcomes. CONCLUSION: An expanded patient-provider visit resulted in greater GERD symptom improvement than a standard empathic medical visit. CIM consultations may have enhanced placebo effects, and further studies to assess the active components of this visit-based intervention are warranted. TRIAL REGISTRATION: ClinicalTrials.gov NCT01915173.