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author:("withan, Mary")
1.  Advances in Integrative Nanomedicine for Improving Infectious Disease Treatment in Public Health 
Introduction
Infectious diseases present public health challenges worldwide. An emerging integrative approach to treating infectious diseases is using nanoparticle (NP) forms of traditional and alternative medicines. Advantages of nanomedicine delivery methods include better disease targeting, especially for intracellular pathogens, ability to cross membranes and enter cells, longer duration drug action, reduced side effects, and cost savings from lower doses.
Methods
We searched Pubmed articles in English with keywords related to nanoparticles and nanomedicine. Nanotechnology terms were also combined with keywords for drug delivery, infectious diseases, herbs, antioxidants, homeopathy, and adaptation.
Results
NPs are very small forms of material substances, measuring 1–100 nanometers along at least one dimension. Compared with bulk forms, NPs’ large ratio of surface-area-to-volume confers increased reactivity and adsorptive capacity, with unique electromagnetic, chemical, biological, and quantum properties. Nanotechnology uses natural botanical agents for green manufacturing of less toxic NPs.
Discussion
Nanoparticle herbs and nutriceuticals can treat infections via improved bioavailability and antiinflammatory, antioxidant, and immunomodulatory effects. Recent studies demonstrate that homeopathic medicines may contain source and/or silica nanoparticles because of their traditional manufacturing processes. Homeopathy, as a form of nanomedicine, has a promising history of treating epidemic infectious diseases, including malaria, leptospirosis and HIV/AIDS, in addition to acute upper respiratory infections. Adaptive changes in the host’s complex networks underlie effects.
Conclusions
Nanomedicine is integrative, blending modern technology with natural products to reduce toxicity and support immune function. Nanomedicine using traditional agents from alternative systems of medicine can facilitate progress in integrative public health approaches to infectious diseases.
doi:10.1016/j.eujim.2012.11.002
PMCID: PMC3685499  PMID: 23795222
Nanomedicine; Drug delivery systems; Medicinal plants; Herbal medicine; Antioxidants; Homeopathy; Nanoparticles; Silica; Infectious disease treatment; Adaptation; Network medicine
2.  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.
doi:10.1016/j.homp.2012.10.005
PMCID: PMC3539158  PMID: 23290882
nanoparticle; homeopathy; allostasis; time-dependent sensitization; metaplasticity; crosssensitization; research design; complex adaptive systems; physiological stress response
3.  Surgical Treatment Differences Among Latina and African American Breast Cancer Survivors 
Oncology nursing forum  2012;39(4):E324-E331.
Purpose/Objectives
To describe breast cancer treatment choices from the perspectives of Latina and African American breast cancer survivors.
Design
An interdisciplinary team conducted a mixed-methods study of women treated for stages I–IV breast cancer.
Setting
Participants’ homes in metropolitan areas.
Sample
39 participants in three groups: monolingual Spanish-speaking Latinas (n = 15), English-speaking Latinas (n = 15), and African American women (n = 9).
Methods
Individual participant interviews were conducted by racially and linguistically matched nurse researchers, and sociodemographic data were collected. Content and matrix analysis methods were used.
Main Research Variables
Perceptions of breast cancer care.
Findings
High rates of mastectomy were noted for early-stage treatment (stage I or II). Among the participants diagnosed with early-stage breast cancer, the majority of English-speaking Latinas (n = 9) and African American women (n = 4) received a mastectomy. However, the majority of the Spanish-speaking Latina group (n = 5) received breast-conserving surgery. Four factors influenced the choice of mastectomy over lumpectomy across the three groups: clinical indicators, fear of recurrence, avoidance of adjuvant side effects, and perceived favorable survival outcomes. Spanish-speaking Latinas were more likely to rely on physician treatment recommendations, and the other two groups used a shared decision-making style.
Conclusions
Additional study is needed to understand how women select and integrate treatment information with the recommendations they receive from healthcare providers. Among the Spanish-speaking Latina group, limited English proficiency, the use of translators in explaining treatment options, and a lack of available educational materials in Spanish are factors that influenced reliance on physician recommendations.
Implications for Nursing
Oncology nurses were notably absent in supporting the women’s treatment decision making. Advanced practice oncology nurses, coupled with language-appropriate educational resources, may provide essential guidance in clarifying surgical treatment choices for breast cancer among culturally and linguistically diverse populations.
doi:10.1188/12.ONF.E324-E331
PMCID: PMC3495184  PMID: 22750902
4.  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.
doi:10.1186/1472-6882-12-191
PMCID: PMC3570304  PMID: 23088629
Homeopathy; Nanoparticles; Silica; Epitaxy; Hormesis; Cross adaptation; Time dependent sensitization; Metaplasticity; Allostasis; Complex adaptive system; Stress response network; Resilience; Nanomedicine
5.  Analyzing Heterogeneous Complexity in Complementary and Alternative Medicine Research: A Systems Biology Solution via Parsimony Phylogenetics 
Summary
Systems biology offers cutting-edge tools for the study of complementary and alternative medicine (CAM). The advent of ‘omics’ techniques and the resulting avalanche of scientific data have introduced an unprecedented level of complexity and heterogeneous data to biomedical research, leading to the development of novel research approaches. Statistical averaging has its limitations and is unsuitable for the analysis of heterogeneity, as it masks diversity by homogenizing otherwise heterogeneous populations. Unfortunately, most researchers are unaware of alternative methods of analysis capable of accounting for individual variability. This paper describes a systems biology solution to data complexity through the application of parsimony phylogenetic analysis. Maximum parsimony (MP) provides a data-based modeling paradigm that will permit a priori stratification of the study cohort(s), better assessment of early diagnosis, prognosis, and treatment efficacy within each stratum, and a method that could be used to explore, identify and describe complex human patterning.
doi:10.1159/000335190
PMCID: PMC3292783  PMID: 22327551
Heterogeneity; Parsimony; Phylogenetics; Synapomorphies; Systems biology; Clinical trial design; Complementary and alternative medicine
6.  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.
doi:10.1186/1472-6882-11-135
PMCID: PMC3293761  PMID: 22206345
Complementary and alternative medicine (CAM); patient-reported outcomes (PROs); patient-centered care; non-specific outcomes; questionnaire development; retrospective pre-test; well-being
7.  New Approaches to Nutritional Therapy 
doi:10.1016/j.nurpra.2010.07.001
PMCID: PMC2976542  PMID: 21076654
8.  COMPLEMENTARY THERAPY USE AMONG RACIAL/ETHNIC GROUPS 
doi:10.1016/j.nurpra.2010.05.001
PMCID: PMC2975464  PMID: 21072254
10.  Indigenous Native American Healing Traditions 
doi:10.1016/j.nurpra.2010.03.016
PMCID: PMC2913884  PMID: 20689671
11.  Promoting Optimal Health with Traditional Chinese Medicine 
doi:10.1016/j.nurpra.2010.01.013
PMCID: PMC2913879  PMID: 20689727
12.  Using Herbal Remedies to Maintain Optimal Weight 
doi:10.1016/j.nurpra.2009.12.005
PMCID: PMC2927017  PMID: 20802831
13.  Naturopathic Treatment of Obesity 
doi:10.1016/j.nurpra.2009.07.019
PMCID: PMC2791327  PMID: 20161459
14.  The Inner Healer: Mind-body Strategies for Health 
doi:10.1016/j.nurpra.2009.01.012
PMCID: PMC2754856  PMID: 20160987
15.  Let’s Talk about Complementary and Alternative Therapies 
doi:10.1016/j.nurpra.2008.12.011
PMCID: PMC2754875  PMID: 20160990
16.  Mind-Body Solutions for Obesity 
doi:10.1016/j.nurpra.2009.05.012
PMCID: PMC2764526  PMID: 20046886
17.  Introducing Complementary and Alternative Therapies 
doi:10.1016/j.nurpra.2008.10.012
PMCID: PMC2754854  PMID: 20046927
18.  Counternarratives of Mexican-Origin Women with Breast Cancer 
ANS. Advances in nursing science  2009;32(2):E57-E67.
Little is known about cancer health disparities among undocumented Latino immigrant populations, who represent a rapidly growing sector in the United States. Federal and state legislative reforms to control immigration have increased significantly over the past year. Although the effects of immigration reforms are being documented in housing, education, and public service industries, no data have been found examining the impact on the health of immigrant communities. In this article, we identify the consequences of recent immigration legislation enacted in Arizona, which has created barriers to accessing cancer treatment and continued follow-up care among a sample of Latina breast cancer survivors.
doi:10.1097/ANS.0b013e3181a3b47c
PMCID: PMC2712628  PMID: 19461222
access to care; breast cancer; health disparities; health policy; immigration; Latino; undocumented
19.  Evaluating Complex Healthcare Systems: A Critique of Four Approaches 
The purpose of this paper is to bring clarity to the emerging conceptual and methodological literature that focuses on understanding and evaluating complex or ‘whole’ systems of healthcare. An international working group reviewed literature from interdisciplinary or interprofessional groups describing approaches to the evaluation of complex systems of healthcare. The following four key approaches were identified: a framework from the MRC (UK), whole systems research, whole medical systems research described by NCCAM (USA) and a model from NAFKAM (Norway). Main areas of congruence include acknowledgment of the inherent complexity of many healthcare interventions and the need to find new ways to evaluate these; the need to describe and understand the components of complex interventions in context (as they are actually practiced); the necessity of using mixed methods including randomized clinical trials (RCTs) (explanatory and pragmatic) and qualitative approaches; the perceived benefits of a multidisciplinary team approach to research; and the understanding that methodological developments in this field can be applied to both complementary and alternative medicine (CAM) as well as conventional therapies. In contrast, the approaches differ in the following ways: terminology used, the extent to which the approach attempts to be applicable to both CAM and conventional medical interventions; the prioritization of research questions (in order of what should be done first) especially with respect to how the ‘definitive’ RCT fits into the process of assessing complex healthcare systems; and the need for a staged approach. There appears to be a growing international understanding of the need for a new perspective on assessing complex healthcare systems.
doi:10.1093/ecam/nel079
PMCID: PMC1978227  PMID: 17965757
complex interventions; research methods; whole systems research
20.  Competency-based evaluation tools for integrative medicine training in family medicine residency: a pilot study 
Background
As more integrative medicine educational content is integrated into conventional family medicine teaching, the need for effective evaluation strategies grows. Through the Integrative Family Medicine program, a six site pilot program of a four year residency training model combining integrative medicine and family medicine training, we have developed and tested a set of competency-based evaluation tools to assess residents' skills in integrative medicine history-taking and treatment planning. This paper presents the results from the implementation of direct observation and treatment plan evaluation tools, as well as the results of two Objective Structured Clinical Examinations (OSCEs) developed for the program.
Methods
The direct observation (DO) and treatment plan (TP) evaluation tools developed for the IFM program were implemented by faculty at each of the six sites during the PGY-4 year (n = 11 on DO and n = 8 on TP). The OSCE I was implemented first in 2005 (n = 6), revised and then implemented with a second class of IFM participants in 2006 (n = 7). OSCE II was implemented in fall 2005 with only one class of IFM participants (n = 6).
Data from the initial implementation of these tools are described using descriptive statistics.
Results
Results from the implementation of these tools at the IFM sites suggest that we need more emphasis in our curriculum on incorporating spirituality into history-taking and treatment planning, and more training for IFM residents on effective assessment of readiness for change and strategies for delivering integrative medicine treatment recommendations. Focusing our OSCE assessment more narrowly on integrative medicine history-taking skills was much more effective in delineating strengths and weaknesses in our residents' performance than using the OSCE for both integrative and more basic communication competencies.
Conclusion
As these tools are refined further they will be of value both in improving our teaching in the IFM program and as competency-based evaluation resources for the expanding number of family medicine residency programs incorporating integrative medicine into their curriculum. The next stages of work on these instruments will involve establishing inter-rater reliability and defining more clearly the specific behaviors which we believe establish competency in the integrative medicine skills defined for the program.
doi:10.1186/1472-6920-7-7
PMCID: PMC1855050  PMID: 17442108
21.  Researching complementary and alternative treatments – the gatekeepers are not at home 
Background
To explore the strengths and weaknesses of conventional biomedical research strategies and methods as applied to complementary and alternative medicine (CAM), and to suggest a new research framework for assessing these treatment modalities.
Discussion
There appears to be a gap between published studies showing little or no efficacy of CAM, and reports of substantial clinical benefit from patients and CAM practitioners. This "gap" might be partially due to the current focus on placebo-controlled randomized trials, which are appropriately designed to answer questions about the efficacy and safety of pharmaceutical agents. In an attempt to fit this assessment strategy, complex CAM treatment approaches have been dissected into standardized and often simplified treatment methods, and outcomes have been limited.
Unlike conventional medicine, CAM has no regulatory or financial gatekeeper controlling their therapeutic "agents" before they are marketed. Treatments may thus be in widespread use before researchers know of their existence. In addition, the treatments are often provided as an integrated 'whole system' of care, without careful consideration of the safety issue.
We propose a five-phase strategy for assessing CAM built on the acknowledgement of the inherent, unique aspects of CAM treatments and their regulatory status in most Western countries. These phases comprise:
1. Context, paradigms, philosophical understanding and utilization
2. Safety status
3. Comparative effectiveness.
4. Component efficacy
5. Biological mechanisms.
Summary
Using the proposed strategy will generate evidence relevant to clinical practice, while acknowledging the absence of regulatory and financial gatekeepers for CAM. It will also emphasize the important but subtle differences between CAM and conventional medical practice.
doi:10.1186/1471-2288-7-7
PMCID: PMC1800863  PMID: 17291355
22.  Developing CAM Research Capacity for Complementary Medicine 
This article describes initiatives that have been central to the development of complementary and alternative medicine (CAM) research capacity in the United Kingdom, Canada and the United States over the last decade. While education and service delivery are essential parts of the development of CAM, this article will focus solely on the development of research strategy. The development of CAM research has been championed by both patients and politicians, primarily so that we may better understand the popularity and apparent effectiveness of these therapies and support integration of safe and effective CAM in health care. We hope that the perspective provided by this article will inform future research policy.
doi:10.1093/ecam/nel007
PMCID: PMC1475932  PMID: 16786061
CAM; research; strategy; US; UK; Canada

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