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OBJECTIVE: To evaluate whether micronutrients (vitamins/minerals) benefit attention-deficit/hyperactivity disorder (ADHD) and irritability in a North American pediatric sample. METHOD: A three-site 8-week placebo-controlled randomized clinical trial of micronutrients was conducted in unmedicated children ages 6-12 with ADHD and at least one impairing irritability symptom by parent report on the Child and Adolescent Symptom Inventory-5 (CASI-5). A priori-defined primary outcomes were Clinical Global Impression-Improvement (CGI-I) (CGI-I of 1 or 2 = treatment responder) and parent-rated CASI-5 composite score of ADHD, oppositional defiant, disruptive mood dysregulation, and peer conflict symptoms, including impairment scores. RESULTS: Of 135 randomized (mean age 9.8 years), 126 (93%) comprised the modified intention-to-treat population. Blinding was maintained. For the CGI-I, 54% of the micronutrient and 18% of the placebo group were responders (Risk Ratio=2.97, 97.5% CI: 1.50, 5.90, p

African immigrant women are underrepresented in health research on maternal mental health. Thus, there is a need to highlight successful recruitment strategies to engage African women in health-oriented research. This paper offers insights on recruitment strategies utilized in recruiting African immigrant women in Alberta (Canada) with infants 2 years of age or under for a survey study on maternal mental health. We recruited 136 African immigrant women. Most participants were recruited by using already established social networks in the community. Other successful strategies included referral from community partners (i.e., immigrant organizations, cultural association, religious institutions), participants, utilizing an online survey tool (i.e., Qualtrics), and through family and friend networks (i.e., word-of-mouth). This study evidently highlights the importance of utilizing multiple recruitment strategies to successfully meet the desired sample size for a survey study. We believe the lessons learned during the process of recruitment will be helpful for others working with other African immigrant women populations in Canada and in other Western societies.

OBJECTIVES: The inflammatory biomarker C-reactive protein (CRP) measures systemic inflammation and has been shown to be increased in patients with mood disorders such as depression. The objective of this study was to determine the association between self-reported mood disorders with CRP levels in a representative sample of the Canadian population using the Canadian Health Measures Survey (CHMS) data 2013–2014. METHODS: The CHMS is an ongoing national cross-sectional survey of Canadians about their general health. The current study used the data collected from Cycle 3 (2012/13) and was limited to adults aged 18 and older. Survey weights were assigned to adjust for non-response and non-random sample selection of the responding sample. RESULTS: Data were analyzed from 5782 respondents (400 (6.9%) self-reported mood disorders and 5382 (93.1%) reported no mood disorders). The CRP level was significantly higher among those with mood disorders than among those without (3.22 (0.17) vs. 2.34 (0.04) mg/L, p = 0.003). Respondents with CRP levels > 10.00 mg/L had 2.69 greater odds of reporting a mood disorder compared with those with CRP levels ≤ 1.00 mg/L (p = 0.02). Higher proportions of respondents with mood disorders were older, had lower BMI, had secondary education, had weak sense of community, had higher proportion of asthma or arthritis, were current/past smokers, had daily consumption of 3+ drinks of alcohol, and used prescription drugs, cannabis/hashish, or other drugs compared with those without mood disorders (all p’s

Background: Lymphedema has been a prevalent and often severe side effect for patients receiving treatment for breast cancer typically resulting in physical and psychosocial distress as well as decreased quality of life. With no widely effective or safe drug treatment(s) for lymphedema, this study aimed to assess the efficacy of combined Lymphdiaral™ drops and ointment for treatment-related lymphedema. Methods: This open label, randomized, parallel-group trial ran over 12 weeks with a final follow-up visit at 24 weeks. One hundred and thirty-four (n = 134) patients were consented to the study. Of these, 119 patients were randomized to either standard care group (compression garment) or treatment group (compression garment plus Lymphdiaral™ drops and ointment) and follow-up data was obtained. The primary objective was the reduction in lymphedema as measured by change in arm volume. Results: The values for the arm volumes did not show a statistically significant decrease in both the standard care or treatment groups. Additionally, there was no statistical difference in arm volume reduction between the groups. Conclusions: This first randomized trial shows, that the homeopathic drug combination of Lymphdiaral™ drops and ointment does not improve lymphedema in breast cancer patients. Citation Format: Jawaid Younus, Morgan Black, Lyn Kligman, Brenda Leung. Efficacy of Lymphdiaral™ in breast cancer patients with lymphedema [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-12-15.

ObjectivesNaturopathy is a traditional medicine system informed by codified philosophies and principles, and an emphasis on non-pharmacologic therapeutic interventions. While naturopathy is practiced by approximately 75 000 to 100 000 naturopathic practitioners in at least 98 countries, little is known about the international prevalence of history of consultation with a naturopathic practitioner. This study reports a systematic review and meta-analysis of studies describing the global prevalence of history of consultation with a naturopathic practitioner by the general population.SettingThe included literature was identified through a systematic search of eight databases between September and October 2019, as well as the grey literature.ParticipantsStudies were included if they reported the prevalence rate of consultations with a naturopathic practitioner by the general populationInterventionsSurvey items needed to report consultations with a naturopathic practitioner as defined in the country where data was collected, and not combine naturopathic consultations with other health services or only report consulations for illness populations.Primary and secondary outcome measuresPrimary measures used for the analysis was consultations in the previous 12-months. Other prevalence timeframes were reported as secondary measures.MethodsMeta-analysis of prevalence data was conducted using random effects models based on individual countries and World Health Organisation (WHO) world regions.ResultsThe literature search identified eight manuscripts summarizing 13 studies reporting prevalence for inclusion in the review. All included studies had a low risk of bias. Meta-analysis of the included studies by world region found the 12-month prevalence of history of naturopathy consultations ranged from 1% in the Region of the Americas to 6% in the European and Western Pacific Regions.ConclusionsThere are up to 6-fold differences in the prevalence of naturopathy consults over 12-months between and within world regions, which may be driven by a range of policy, legislative and social factors.Strengths andLimitations of this studyNaturopathy is one of the most commonly used traditional and complementary medicines in the Western world and this is the first systematic review and meta-analysis reporting the prevalence of consutations with a naturopathic practitioner.This study includes only includes data published after 2010 to ensure the results are contemporary, however this may have excluded some studies in countries with older data.The results are limited by the poor availability of data reporting consultations with a naturopathic practitioner, including in countries where a large number of naturopathic practitioners are known to provide care.

Aim To describe the prevalence of health care utilisation and out-of-pocket expenditure associated with the management of diabetes among Australian women aged 45 years and older. Design Cross-sectional survey design. Methods The questionnaire was administered to 392 women (a cohort of the 45 and Up Study) reporting a diagnosis of diabetes between August and November 2016. It asked about the use of conventional medicine, complementary medicine (CM) and self-prescribed treatments for diabetes and associated out-of-pocket spending. Results Most women (88.3%; n = 346) consulted at least one health care practitioner in the previous 12 months for their diabetes; 84.6% (n = 332) consulted a doctor, 44.4% (n = 174) consulted an allied health practitioner, and 20.4% (n = 80) consulted a CM practitioner. On average, the combined annual out-of-pocket health care expenditure was AU$492.6 per woman, which extrapolated to approximately AU$252 million per annum. Of this total figure, approximately AU$70 million was spent on CM per annum. Conclusions Women with diabetes use a diverse range of health services and incur significant out-of-pocket expense to manage their health. The degree to which the health care services women received were coordinated, or addressed their needs and preferences, warrants further exploration. Limitations of this study include the use of self-report and inability to generalise findings to other populations.

To describe the trends in the prevalence and incidence of children with psychiatric disorders, the types of medication prescribed, and the type of physician providing the prescriptions. This retrospective study linked six population-based administrative databases (2008–2015) in Alberta, Canada. The prevalence of paediatric psychiatric disorders increased from 12.6 per 100 population in 2008 to 15.0 per 100 population in 2015, while the incidence rate increased from 2.0 per 100 population to 2.2 per 100 population in the same period. The proportion of patients dispensed any psychiatric medication increased from 21.4% in 2008 to 28.2% in 2015. Over the same period, dispensations for antidepressants increased from 7.0% to 11.2% and stimulants to treat ADHD, from 11.9% to 15.9%. For antidepressants, general practitioners (GPs) wrote the highest proportion of prescriptions (44.3% in 2011–48.1% in 2015), while paediatricians wrote the lowest proportion (8.7% in 2011–11.0% in 2015) and the proportion by psychiatrists decreased from 33.4% in 2011 to 27.2% in 2015. For stimulants to treat ADHD, paediatricians were the most frequent prescribers (36.9% in 2011–39.3% in 2015) followed by GPs as the second most frequent (33.1% in 2011–33.5% in 2015), while psychiatrists were the least likely to prescribe stimulants for ADHD. The increasing trend of psychiatric diagnoses and medication prescriptions in the paediatric population is evident using population-based administrative databases. The lack of safety and adverse consequences of medication use in this cohort warrants additional monitoring data.

Aims Maternal metabolic disorders place the mother at risk for negative pregnancy outcomes with potentially long‐term health impacts for the child. Metabolic syndrome, a cluster of features associated with increased risk of metabolic disorders, such as cardiovascular disease, diabetes and stroke, affects roughly one in five Canadians. Metabolomics is a relatively new technique that may be a useful tool to identify women at risk of metabolic disorders. This study set out to characterize urinary metabolic biomarkers of pregnant women with obesity and of pregnant women who later developed gestational diabetes mellitus (pre‐GDM), compared to controls. Methods and Materials Second trimester urine samples were collected through the Alberta Pregnancy Outcomes and Nutrition (APrON) cohort and examined with 1H nuclear magnetic resonance (NMR) spectroscopy. Multivariate analysis was used to examine group differences, and machine learning feature selection tools identified the metabolites contributing to separation. Results Obesity and pre‐GDM metabolomes were distinct from controls and from each other. In each comparison, the glycine, serine and threonine pathways were the most impacted. Pantothenate, formic acid and glycine were downregulated by obesity, while formic acid, dimethylamine and galactose were downregulated in pre‐GDM. The three most impacted metabolites for the comparison of obesity versus pre‐GDM groups were upregulated creatine/caffeine, downregulated sarcosine/dimethylamine and upregulated maltose/sucrose in individuals who later developed GDM. Conclusion These findings suggest a role for urinary metabolomics in the prediction of GDM and metabolic marker identification for potential diagnostics and prognostics in women at risk., Urinary metabolomics can provide diagnostic signatures of obesity in pregnant mothers. The urine metabolome can predict the risk of gestational diabetes mellitus. Proton nuclear magnetic resonance spectroscopy is able to identify metabolic markers for diagnostics and prognostics in women at risk.

IntroductionAttention-deficit/hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders of childhood. Up to 50% of children with ADHD may also experience symptoms of emotional dysregulation, such as anger, irritability, and aggression. Emotional dysregulation contributes to adverse health outcomes such as depression and peer problems, yet it is poorly understood, and effective treatment options are lacking. Emerging evidence suggests that sensory processing may play a role in emotional dysregulation. Forty to 50% of children with ADHD may also experience sensory modulation dysfunction, or SMD. SMD is characterized by hypo- or hyperreactivity to pain and sensation. Only one study investigated the relationship of SMD and emotional dysregulation in ADHD; they found a correlation of r=0.45. If SMD drives emotional dysregulation in ADHD, treating SMD has the potential to improve emotional regulation. Further evaluating the relationship between SMD and emotional dysregulation in ADHD is the crucial first step in developing effective treatment options.MethodsData for this analysis are derived from the baseline assessment of a multi-site, randomized, controlled trial: The Micronutrients for ADHD in Youth (MADDY) Study. The study enrolled children aged 6-12 with a diagnosis of ADHD and symptoms of emotional dysregulation. Using a cross-sectional study design, we will measure the association between emotional dysregulation and SMD at baseline. Emotional dysregulation was measured using the Strengths and Difficulties Questionnaire (SDQ) and a composite score from the Child and Adolescent Symptom Inventory, Version-5 (CASI-5). SMD will be assessed using two subscales from the Temperament in Middle Childhood Questionnaire (TMCQ). To test our hypothesis, we will use simple linear regression. Models will be adjusted for potential confounding variables.ConclusionOur results will serve to better characterize the relationship between SMD and emotional dysregulation in children with ADHD, which may inform treatment options and diminish adverse health outcomes.

Objective: Study goals were to (1) provide a rationale for developing a composite primary outcome score that includes symptom severity for attention-deficit/hyperactivity disorder (ADHD) and emotional dysregulation, plus symptom-induced impairment; (2) demonstrate weighting methods to calculate the composite score using a sample of children diagnosed with ADHD and aggression; and (3) identify the optimal weighting method most sensitive to change, as measured by effect sizes. Methods: We conducted secondary data analyses from the previously conducted Treatment of Severe Childhood Aggression (TOSCA) study. Children aged 6-12 years were recruited through academic medical centers or community referrals. The composite primary outcome comprised the ADHD, oppositional defiant disorder, disruptive mood dysregulation disorder, and peer conflict subscales from the Child and Adolescent Symptom Inventory (CASI), a DSM (Diagnostic and Statistical Manual)-referenced rating scale of symptom severity and symptom-induced impairment. Five weighting methods were tested based on input from senior statisticians. Results: The composite score demonstrated a larger (Cohen's d) effect size than the individual CASI subscales, irrespective of the weighting method (10%-55% larger). Across all weighting methods, effect sizes were similar and substantial: approximately a two-standard deviation symptom reduction (range: -1.97 to -2.04), highest for equal item and equal subscale weighting, was demonstrated, from baseline to week 9, among all TOSCA participants. The composite score showed a medium positive correlation with the Clinical Global Impressions-Severity scores, 0.46-0.47 for all weighting methods. Conclusions: A composite score that included severity and impairment ratings of ADHD and emotional dysregulation demonstrated a more robust pre-post change than individual subscales. This composite may be a more useful indicator of clinically relevant improvement in heterogeneous samples with ADHD than single subscales, avoiding some of the statistical limitations associated with multiple comparisons. Among the five similar weighting methods, the two best appear to be the equal item and equal subscale weighting methods.

AIM This pilot study investigated the use of acupuncture in the treatment of paediatric anxiety. METHODS Children with anxiety, aged 8-16, were randomised to either the acupuncture or waitlist control groups. Anxiety was measured using the Hamilton Anxiety Rating Scale (HAM-A) for children and adolescents with generalised anxiety disorder and Multidimensional Anxiety Scale for Children 2nd Edition (MASC-2) self-rated and parent-rated forms. RESULTS Twenty participants were enrolled in the study and 19 completed all the questionnaires to be included in the analysis. There were no differences in socio-demographic characteristics at baseline between the two groups. At the second assessment, the mean MASC-parent score for the acupuncture group was significantly lower than the waitlist group (65.6 (SD 15.0) compared to 81.0 (SD 11.9), P = 0.025) with an effect size = 1.13. The pre- and post-treatment comparisons were also significantly lower for both groups in the anxiety measures. In the acupuncture group, MASC-parent (P = 0.008, effect size 0.75) and the HAM-A (P < 0.001, effect size 1.4). In the waitlist group, MASC-self (P = 0.022; effect size 0.4), MASC-parent (P = 0.048; effect size 0.75) and HAM-A (P = 0.007; effect size 1.21). CONCLUSIONS This study provided promising results on the potential use of acupuncture to treat children and adolescents with general anxiety. Future research using a randomised control trial with a sufficient sample size to control for confounders and sham (placebo) comparators is warranted.

These comments include established behavioral treatment preceding and augmenting stimulant use to prevent or reduce dosing, nutritional approaches with placebo-controlled evidence, and possible effects of stimulant on micronutrient levels.

Background: Special diets are frequently used by the public but reasons for use and characteristics of users remain unclear.AIM: To determine prevalence of the use of special diets, the individual characteristics associated with their use and reasons for use. Methods: The secondary analysis used data from the 2012 National Health Interview Survey (NHIS), a cross-sectional household interview survey of a nationally representative sample of non-hospitalized US adult populations ( n = 34,525). The dependent variables in this secondary analysis were the use of a special diet (vegetarian, macrobiotic, Atkins, Pritikin, and Ornish) ever and during the past 12 months. Independent variables included sociodemographic, clinical and behavioral variables. Prevalence of special diet use and reasons for use were analyzed descriptively. Associations between independent and dependent variables were analyzed using Chi-square tests and logistic regression. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Results: Lifetime and 12-month prevalence of using special diets were 7.5% (weighted n = 17.7 million) and 2.9% (weighted n = 6.9 million), respectively. Individuals using special diets in the past 12 months were more likely female (OR = 1.45; 95% CI = 1.21-1.74), not married (OR = 0.76; 95% CI = 0.63-0.91), college-educated (OR = 1.98; 95% CI = 1.25-3.11) and depressed (OR = 1.50; 95% CI = 1.14-1.98). They more likely also used herbal products (OR = 2.35; 95%CI = 1.84-2.99), non-vitamin (OR = 1.82; 95% CI = 1.45-2.27) and vitamin supplements (OR = 1.57; 95% CI = 1.24-1.99). Diets were mainly used to improve overall health (76.7%) or for general wellness/prevention (70.4%). Conclusions: Special diets are mainly used for unspecific health reasons by those who are females, have a college degree or with depression, and commonly used in conjunction with herbs and dietary supplements. Refereed/Peer-reviewed

Background and objectives: Complementary and alternative medicine (CAM) use has been associated with preventive health behaviors. However, the role of CAM use in patients&rsquo, health behaviors remains unclear. This study aimed to determine the extent to which patients report that CAM use motivates them to make changes to their health behaviors. Materials and Methods: This secondary analysis of 2012 National Health Interview Survey data involved 10,201 CAM users living in the United States who identified up to three CAM therapies most important to their health. Analyses assessed the extent to which participants reported that their CAM use motivated positive health behavior changes, specifically: eating healthier, eating more organic foods, cutting back/stopping drinking alcohol, cutting back/quitting smoking cigarettes, and/or exercising more regularly. Results: Overall, 45.4% of CAM users reported being motivated by CAM to make positive health behavior changes, including exercising more regularly (34.9%), eating healthier (31.4%), eating more organic foods (17.2%), reducing/stopping smoking (16.6% of smokers), or reducing/stopping drinking alcohol (8.7% of drinkers). Individual CAM therapies motivated positive health behavior changes in 22% (massage) to 81% (special diets) of users. People were more likely to report being motivated to change health behaviors if they were: aged 18&ndash, 64 compared to those aged over 65 years, of female gender, not in a relationship, of Hispanic or Black ethnicity, compared to White, reporting at least college education, compared to people with less than high school education, without health insurance. Conclusions: A sizeable proportion of respondents were motivated by their CAM use to undertake health behavior changes. CAM practices and practitioners could help improve patients&rsquo, health behavior and have potentially significant implications for public health and preventive medicine initiatives, this warrants further research attention.

Background Prenatal and postnatal depressive symptoms are common in expectant and new mothers and fathers. This study examined the association between four patterns of probable perinatal depression (mother depressed, father depressed, both depressed, neither depressed) in co-parenting mothers and fathers and their children’s internalizing and externalizing behaviours at 24 and 36 months of age. The influence of sociodemographic, risk and protective factors was also examined. Methods Depressive symptoms were measured during pregnancy and at 3 months postpartum and children’s behaviour was assessed at 24 and 36 months of age. Families (n = 634) provided data on their children’s internalizing (i.e. emotionally reactive, anxious/depressed, somatic complaints, withdrawn and total) and externalizing (i.e. attention problems, aggression and total) behaviour. Marginal models were employed to determine the relationship between children’s behaviour over the two time points and the four patterns of probable parental depression. Sociodemographic variables as well as risk (stress) and protective (social support) factors were included in these models. Results In the perinatal period 19.40% (n = 123) of mothers scored as probably depressed and 10.57% (n = 67) of fathers. In 6.31% (n = 40) of the participating families, both parents scored as probably depressed and in 63.72% (n = 404) neither parent scored as depressed. For children’s emotionally reactive, withdrawn and total internalizing behaviours, both mothers’ probable depression and mothers and fathers’ co-occurring probable depression predicted higher scores, while for children’s aggressive behaviour, attention problems, and total externalizing behaviours, only mothers’ probable depression predicted higher scores, controlling for sociodemographic, risk and protective factors. Conclusions While probable perinatal depression in mothers predicted 2 and 3 year-old children’s behavioural problems, co-occurrence of depression in mothers and fathers had an increased association with internalizing behavioural problems, after considering sociodemographic, risk and protective factors. Health care providers are encouraged to consider the whole family in preventing and treating perinatal depression.

© 2019 American Academy of Physical Medicine and Rehabilitation Background: The use of complementary and alternative medicine (CAM) therapies have been reported for the management of arthritis. However, little is known about CAM use among adults with self-reported doctor-diagnosed arthritis. Objectives: To determine (1) the prevalence and type of CAM use, (2) the difference in characteristics between CAM users and non-CAM users, and (3) the factors related to CAM use, among U.S. adults with self-reported doctor-diagnosed arthritis. Design: Secondary analysis of the 2012 National Health Interview Survey (NHIS) data. Setting: The NHIS is a cross-sectional survey that gathers health-related data on the civilian, noninstitutionalized U.S. population. Participants: The NHIS 2012 uses a complex, multistage sampling design and oversamples minorities to achieve population representation; it included 34 525 adults, with 7179 adults having arthritis. Methods: Data were analyzed using Stata 15.1 survey syntax. The potential factors related to CAM use included sociodemographics and health-related characteristics. Main Outcome Measurements: CAM modalities were categorized into six groups: natural products, manipulative therapies, mind-body therapies, special diets, movement therapies, and other practitioner-based CAM modalities. Results: Of the adults with arthritis, 2428 (weighted estimate of 36.2% of U.S. adult population) had used CAM within the last year. Adults with arthritis reported greater use of CAM than those without, particularly the use of natural products, manipulative therapies and other practitioner-based CAM modalities. Factors associated with higher CAM use included being female, residing in regions other than the U.S. South, having a college degree or higher, reporting very good/excellent self-rated health status, and having current symptoms of joint stiffness/pain. Conclusion: As more than one-third of U.S. adults with arthritis seek CAM therapies, open and nonjudgmental conversations between conventional medicine providers, CAM providers, and patients should be encouraged to ensure patient health care needs are being met. Level of Evidence: III.

Issue addressed The smoking rate among male Chinese migrants in Australia is higher than among the general population. This study investigated the smoking rate of male Chinese restaurant workers in metropolitan Sydney, and explored factors associated with smoking and quitting. Methods A self-administered questionnaire survey was completed by Chinese workers in selected Chinese restaurants in metropolitan Sydney from October-December 2012. Eighty-nine Chinese restaurants were approached and 54 (61%) took part in the study. The questionnaire asked participants about their smoking status, knowledge of and attitudes to smoking and quitting as well as socio-demographic information. Multivariable logistic regression was built to assess the associated factors. Results Of the 382 participants who completed the survey, 171 (45%) were current smokers and 50% of current smokers wanted to quit smoking. Participants who spoke Mandarin, had lower English proficiency, did not realise environmental smoke harms children, did not prefer a smoke-free environment or had more than 50% of relatives or friends who smoked were more likely to be current smokers. Participants who were aged 18-29 years, did not understand the benefits of quitting smoking or did not prefer a smoke-free environment were less likely to want to quit. Conclusions Nearly 50% of male Chinese restaurant workers surveyed in this study were current smokers. Key factors associated with the participants' smoking or quitting status are: aged 18-29 years; speaking Mandarin; lower English literacy; and not knowing the dangers of smoking. So what? Tobacco control programs targetted at male Chinese restaurant workers that raise awareness of the harm caused by smoking and the benefits of quitting smoking are required to enhance intention to quit smoking within this population.

OBJECTIVES: Attention-deficit/hyperactivity disorder (ADHD) is a neuropsychiatric disorder commonly diagnosed in childhood. Current pharmaceutical treatment options provide a poor long-term risk: benefit ratio with little knowledge of the long-term effects. A broad-spectrum multi-nutrient formula has shown promise in children, but its effects on nutrient status and the underlying metabolome interactions have not been characterized. METHODS: Blood samples from medication-free children (n = 74) with ADHD enrolled in a double–blind randomized placebo-controlled multinutrient trial (RCT) were collected at baseline and 8 weeks post-intervention. Following RCT is an 8-week open label phase during which all participants took the active supplement. Symptoms were assessed using the Child and Adolescent Symptom Inventory 5. Double-blinded plasma samples will be analyzed for tyrosine, phenylalanine, tryptophan, magnesium, and zinc. Untargeted LC-MS metabolomics using HILIC chromatography and a high resolution QTof will assess very polar analytes in plasma extracts. Linear modeling will elucidate the influence of treatment, sampling time, and ADHD symptom score on plasma nutrient and plasma metabolite concentration. RESULTS: Preliminary findings of the open label phase show a significant improvement in inattention (P = 0.0435), hyperactivity (P = 0.0068), ODD (P = 0.0108) and DMDD (P = 0.0119). We hypothesize that these improvements in ADHD symptoms will be correlated with increased circulating concentrations of tyrosine, phenylalanine, tryptophan, magnesium, zinc, and metabolites involved in neurotransmitter synthesis and/or branched chain amino acid metabolism. CONCLUSIONS: Preliminary findings indicate improvements of ADHD symptoms of inattention, hyperactivity, ODD and DMDD following 8 weeks of open label multi-nutrient supplementation. Results of the double-blinded phase are expected to mirror those observed in the open label phase, with increases in nutrients in those receiving the multinutrient. FUNDING SOURCES: The sample analyses were supported by NIH Award Number Grant P30 CA016058, OSU, and OSUCCC. Foundation for the Center of Excellence in Mental Health, Canada; The Ohio State University Department of Human Sciences, College of Education and Human Ecology; The Ohio State University Wexner Medical Center, Clinical Research Center.

Adverse childhood experiences (ACEs) of parents are associated with a variety of negative health outcomes in offspring. Little is known about the mechanisms by which ACEs are transmitted to the next generation. Given that maternal depression and anxiety are related to ACEs and negatively affect children’s behaviour, these exposures may be pathways between maternal ACEs and child psychopathology. Child sex may modify these associations. Our objectives were to determine: (1) the association between ACEs and children’s behaviour, (2) whether maternal symptoms of prenatal and postnatal depression and anxiety mediate the relationship between maternal ACEs and children’s behaviour, and (3) whether these relationships are moderated by child sex. Pearson correlations and latent path analyses were undertaken using data from 907 children and their mothers enrolled the Alberta Pregnancy Outcomes and Nutrition study. Overall, maternal ACEs were associated with symptoms of anxiety and depression during the perinatal period, and externalizing problems in children. Furthermore, we observed indirect associations between maternal ACEs and children’s internalizing and externalizing problems via maternal anxiety and depression. Sex differences were observed, with boys demonstrating greater vulnerability to the indirect effects of maternal ACEs via both anxiety and depression. Findings suggest that maternal mental health may be a mechanism by which maternal early life adversity is transmitted to children, especially boys. Further research is needed to determine if targeted interventions with women who have both high ACEs and mental health problems can prevent or ameliorate the effects of ACEs on children’s behavioural psychopathology.

Background: Attention-Deficit/Hyperactivity Disorder (ADHD) is a chronic neurodevelopmental disorder affecting up to 9% of children and substantial numbers of adults. Existing pharmacologic treatments often improve symptoms, but concerns exist over side effects, stigma, potential long-term health effects, and residual irritability, often treated with adjunctive antipsychotics. To address public and clinician demand for non-pharmacologic evidence-based treatments, this study will examine efficacy of a 36-ingredient micronutrient (vitamin/mineral) supplement as treatment for children with ADHD and irritability. Methods: An international team of experts in ADHD, mood dysregulation, nutrition, epidemiology, and clinical trials conferred to develop/refine a protocol powered to detect a medium effect. The study will employ a fully-blind randomized controlled trial (RCT) design, comparing the micronutrient supplement to matched placebo in 135 children aged 6–12 with ADHD symptoms and irritability, based on the parent-rated Child and Adolescent Symptom Inventory-5 (CASI-5). Irritability will be measured by at least one symptom of oppositional defiant disorder (ODD) or disruptive mood dysregulation disorder (DMDD). Based on research suggesting an irritable ADHD subtype, the primary outcome will be a composite score comprised of the CASI-5 subscales: ADHD, ODD, DMDD, and the Peer Conflict Scale, which assesses anger and aggression perpetrated towards peers. Participants will provide biological samples (blood, urine, saliva, hair and stool) to explore the micronutrients’ mechanisms of action. Discussion: This study is the first adequately powered RCT in North America to examine both behavioral responses to, and biological mechanisms of, micronutrients for ADHD and irritability in children. If found efficacious, broad-spectrum micronutrients, given at therapeutic doses, may provide an evidence-based alternative to prescription medications for ADHD and associated irritability. Trial registration: NCT03252522. Registered 26 July 2017 Keywords: ADHD, Micronutrients, Vitamins, Minerals, Irritability

Background: Depression and anxiety are routinely screened as part of perinatal care. However, other Axis 1 disorders and specific anxiety disorders are less likely to be screened or assessed as part of obstetric care. The objective of this study was to determine whether the Psychiatric Diagnostic Screening Questionnaire (PDSQ) is a potentially useful tool to screen for psychiatric conditions in pregnant and postpartum women in a community setting. Methods: We compared the prevalence of DSM Axis I disorders obtained on the PDSQ with: (1) the prevalence of these disorders reported in previous studies of pregnant and postpartum women, and (2) scores obtained on the Edinburgh Postpartum Depression Scale (EPDS) and the Symptom Checklist-90-Revised (SCL-90R) anxiety scale. Data were obtained from the Alberta Pregnancy Outcomes and Nutrition (APrON) study. Results: The PDSQ was completed by 1575 women prenatally and 1481 postnatally. The three most prevalent PDSQ conditions were social phobia, somatic disorder, and obsessive–compulsive disorder (OCD). The prevalence of social phobia, alcohol disorder, OCD and psychosis were higher in the APrON cohort compared with statistics in the literature. The proportion of women meeting depression and anxiety cut-offs on the PDSQ were lower than for the EPDS and the SCL-90R. The Cohens Kappa index ( k) indicated poor to fair agreement between the measures in classifying pregnant women as depressed or anxious. Conclusions: The PDSQ subscales may not be appropriate for the pregnant population. Research into instruments more specific to pregnant and postpartum women are needed to determine the prevalence of psychiatric disorders in this population.

The Alberta Pregnancy Outcomes and Nutrition (APrON) study is an ongoing prospective cohort study that recruits pregnant women early in pregnancy and, as of 2012, is following up their infants to 3 years of age. It has currently enrolled approximately 5000 Canadians (2000 pregnant women, their offspring and many of their partners). The primary aims of the APrON study were to determine the relationships between maternal nutrient intake and status, before, during and after gestation, and (1) maternal mood; (2) birth and obstetric outcomes; and (3) infant neurodevelopment. We have collected comprehensive maternal nutrition, anthropometric, biological and mental health data at multiple points in the pregnancy and the post-partum period, as well as obstetrical, birth, health and neurodevelopmental outcomes of these pregnancies. The study continues to follow the infants through to 36 months of age. The current report describes the study design and methods, and findings of some pilot work. The APrON study is a significant resource with opportunities for collaboration.

OBJECTIVES: Attention-deficit/hyperactivity disorder (ADHD) is a neuropsychiatric disorder with increasing global prevalence and high heritability commonly diagnosed in childhood. Current pharmaceutical treatment options provide a poor long-term risk: benefit ratio. Nutrition has significant effects on neurological functioning, and increasing evidence exists to support the use of multinutrients as alternative treatment for ADHD. The goal of this study is to assess the efficacy and tolerability of a multinutrient supplement as an alternative treatment for ADHD and co-occurring mood dysregulation symptoms. METHODS: The Multinutrients in ADHD Youth study is a fully-funded, multi-site, randomized double-blinded clinical trial for adolescents ages 6–12 years (n = 135). The study is 16 weeks in total, with an 8-week randomized controlled trial (RCT) followed by an 8-week open label (OL) phase. During the RCT phase, participants are assigned to either the treatment or placebo group at a 3:2 ratio. Study outcomes of ADHD symptoms include child's inattention, hyperactivity and mood dysregulation, which are assessed using validated questionnaires. Outcome data for the OL phase of the study were analyzed using end of RCT phase as baseline given that the RCT component of the study is still blinded. RESULTS: Preliminary findings based on the OL phase compared ADHD symptoms following 8 weeks of open label supplementation (n = 27 families). A significant decrease in symptom count was found for inattention (P ≤ 0.001), hyperactivity (P ≤ 0.001), ODD (P ≤ 0.001) and DMDD (P ≤ 0.001). CONCLUSIONS: This study is the first adequately powered RCT in North America to investigate the effects of multinutrients supplements on ADHD symptoms among children. Preliminary findings indicate a trend in the improvements of ADHD symptoms of inattention, hyperactivity, ODD and DMDD in the OL phase of the study. FUNDING SOURCES: Foundation for the Center of Excellence in Mental Health, Canada; The Ohio State University Department of Human Sciences, College of Education and Human Ecology; The Ohio State University Wexner Medical Center, Clinical Research Center.

This observation study assessed the utility of an electronic Naturopathic Patient Database at 2 naturopathic teaching clinics as a research and educational tool. Focusing on the whole systems practice of naturopathic medicine using individualized treatment protocols, patients from the Canadian College of Naturopathic Medicine outpatient teaching clinic and the Boucher Institute of Naturopathic Medicine outpatient teaching clinic were assessed. Data were collected on patient demographics, laboratory values, physical measures, treatment protocols, and validated questionnaires. Results showed the Naturopathic Patient Database was able to capture both standardized and individualized measures of care for research purposes. A number of substudies were generated by student interns using the database. Limitations identified included limited resources for training faculty, interns, and administrators on program use and data entry; also, data quality and completeness were problematic. However, the Naturopathic Patient Database captured data on the individualized nature of naturopathic care and had the ability to collect and compare large amounts of data.

Emerging evidence suggests substantial health benefits from using meditation. While there are some indications that the popularity of meditation is increasing, little is known about the prevalence, patterns, and predictors of meditation use in the general population. In this secondary analysis of data from the 2012 US National Health Interview Survey (NHIS) (n = 34,525), lifetime and 12-month prevalence of meditation use were 5.2% and 4.1%, respectively. Compared to non-users, those who had used meditation in the past 12 months were more likely to be 40–64 years, female, non-Hispanic White, living in the West, at least college-educated, not in a relationship, diagnosed with one or more chronic conditions, smoking, consuming alcohol and physically active. Meditation was mainly used for general wellness (76.2%), improving energy (60.0%), and aiding memory or concentration (50.0%). Anxiety (29.2%), stress (21.6%), and depression (17.8%) were the top health problems for which people used meditation; 63.6% reported that meditation had helped a great deal with these conditions. Only 34.8% disclosed their use of meditation with a health provider. These findings indicate that about 9.3 million US adults have used meditation in the past 12 months; and that mental health problems were the most important reason for meditation use.

Objectives: To determine whether acupuncture use, sociodemographic characteristics, and existing health conditions differ between acupuncture-preferred consumers (i.e., those who deem acupuncture to be one of the three most important complementary and alternative medicine [CAM] modalities used) and non-acupuncture-preferred consumers who used acupuncture in the past 12 months Methods: This is a secondary analysis of the National Health Interview Survey Sample Adult File and Adult Alternative Medicine datasets collected by the Centers for Disease Control and Prevention during 2012. The sample was drawn from the noninstitutionalized civilian population of the United States. The datasets yielded 34,525 respondents aged 18 years and older. Measures included in the analysis were acupuncture use in the past 12 months, sociodemographic characteristics, and existing health conditions. Analyses were performed by using Stata software, version 9.0 (Stata Corp., College Station, TX). Results: Of the 10,158 adults who responded to the question regarding the "three most important" CAM modalities used, 572 (5.6%) had used acupuncture in the past 12 months. Of these, 456 (79.7%) chose acupuncture as one of the top three CAM modalities most important to their health. Acupuncture-preferred consumers reported significantly more visits to acupuncturists (7.46 versus 3.99 visits; p < 0.001), as well as higher out-of-pocket costs ($342.8 versus $246.4; p < 0.001), compared with non-acupuncture-preferred consumers. The logistic regression model revealed that with every additional CAM modality used, the likelihood of deeming acupuncture as one of the three CAM modalities most important to one's health decreased by 39% (odds ratio, 0.61; 95% confidence interval, 0.52-0.71; p < 0.001). Health conditions were not statistically significant predictors. Conclusions: A consumer's preference for acupuncture appeared not to be driven by health conditions but rather was related to sociodemographic factors. This suggests that health education regarding acupuncture may need to be tailored to certain consumer groups, such as those residing in the South, and could provide more information on the comparative effectiveness of acupuncture for various health conditions. Refereed/Peer-reviewed

Postpartum depression (PPD) is a growing mental health concern in new mothers and fathers. The purpose of this study was to determine the predictors of depression at 3 months postpartum, comparing depressed couples to couples with only one depressed partner or no depressed partner, using data from the Alberta Pregnancy Outcomes and Nutrition study. Data from mothers and fathers were collected at second trimester and 3 months postpartum. Results showed predictors of PPD in mothers to be low household income, high prenatal depressive symptoms, and postnatally, low social support and higher number of stressful life events. Fathers had similar predictors, including low household income, high prenatal depressive symptoms, and postnatally low social support and smoking. Compared with non-depressed couples, factors that predicted PPD in both mothers and fathers in couples included low income, high prenatal depressive symptoms in mothers and low prenatal social support reported by fathers.

Background: Homeopathy use continues to grow in many European countries, and some studies have examined the characteristics of patients using homeopathy within the general population. The aim of this study was to identify predictors for homeopathy use among internal medicine patients. Patients and Methods: A cross-sectional analysis was conducted among all patients being referred to the Department of Internal and Integrative Medicine at Essen, Germany, over a 3-year period. The analysis examined whether patients had used homeopathy for their primary medical complaint before, the perceived benefit, and the perceived harm of homeopathy use. Odds ratios with 95% confidence intervals were calculated using multiple logistic regression analysis. Results: Of 2,045 respondents, 715 (35.0%) reported having used homeopathy for their primary medical complaint (diagnosis according to the International Statistical Classification of Diseases and Related Health Problems), with 359 (50.2%) reporting perceived benefits and 15 (2.1%) reporting harm. Homeopathy use was positively associated with female gender, high school level education, suffering from fibromyalgia or subthreshold depression, and being fast food abstinent, while patients with osteoarthritis, spinal or other pain, smokers, and patients with a high external-social health locus of control were less likely to use homeopathy. Conclusion: Personal characteristics and health status may impact on the use and the perceived helpfulness of homeopathy.

The Naturopathic Patient Database is a data management tool developed by the Canadian College of Naturopathic Medicine to collect patient data from its teaching clinic, the Robert Schad Naturopathic Clinic. This study investigated how type 2 diabetes mellitus was managed at the Robert Schad Naturopathic Clinic from May 2009 to February 2011. Cases of type 2 diabetes mellitus from the Robert Schad Naturopathic Clinic reported in the Naturopathic Patient Database were extracted based on an International Classification of Diseases, 10th revision code assessment of E11 (non-insulin-dependent diabetes mellitus) and files were audited. The American Diabetes Association 2010 standards of medical care in diabetes were used as guidelines for the audit. Multiple categories in diagnosis, physical exam, laboratory tests, and management were graded on a 0 to 2 scale. The average audit score was 55.5/90. The most common interventions being used are diet and aerobic exercise, followed by supplements (omega-3 fatty acids) and botanicals. These data suggest that the American Diabetes Association standards of care for type 2 diabetes mellitus are not followed stringently. Education and creation of a naturopathic standard of care may improve audit performance and patient outcomes.

Autism spectrum disorder (ASD) is often accompanied by self-injurious behavior (SIB), aggression, and tantrums, symptoms that have reportedly improved with micronutrient (vitamins and minerals) treatment. The current study took advantage of naturally occurring differences in parental preferences for treatment approaches. The micronutrient group asked for treatment without pharmaceuticals (n = 44, aged 2–28 years at entry [M = 8.39 ± 5.58]). Their records were matched with those of 44 similar children whose families requested conventional treatment (medication group). Both groups improved on both the Childhood Autism Rating Scale and the Childhood Psychiatric Rating Scale (all p values

Background: Measures of perceived health status may be vulnerable to ethnic and sociodemographic characteristics. The purpose of this study was to compare self-reported health status in Chinese and whites using 3 measures: physical and mental health status with the 5-point Likert-type scale, the EQ-5D together with a modified health index scale (0–100), and number of chronic conditions. Methods: A cross-sectional telephone survey of Chinese and white Canadians was conducted in a large city in Alberta, Canada. Results: We analyzed 830 Chinese and 789 white respondents. Chinese, compared with whites, reported better health status using the EQ-5D health index (0.94 vs. 0.86) and had fewer chronic conditions surveyed (51.9% vs. 79.2% had one or more conditions). However, Chinese rated their health status fair or poor more often than whites (27.3% vs. 9.7% for physical health and 24.0% vs. 5.0% for mental health) and both groups rated similarly on the health index scale (80.0 for Chinese vs. 77.9 for white). Conclusions: Health status measurements performed inconsistently across ethnic populations. The EQ-5D health index was consistent with the number of chronic conditions, whereas results from the 5-point Likert-type scale and the health index scale were not consistent with the number of chronic conditions. Perceived health status differed by the measures used and ethnicity.

Background Mental disorders are one of the leading contributors to the global burden of disease. The Alberta Pregnancy Outcomes and Nutrition (APrON) study was initiated in 2008 to better understand perinatal environmental impacts on maternal mental health and child development. Aims This pregnancy cohort was established to investigate the relationship between the maternal environment (e.g. nutritional status), maternal mental health status, birth outcomes, and child development. The purpose of this paper is to describe the creation of this longitudinal cohort, the data collection tools and procedures, and the background characteristics of the participants. Subjects Participants were pregnant women age 16 or older, their infants and the biological fathers. Outcome measures For the women, data were collected during each trimester of pregnancy and at 3, 6, 12, 24, and 36months after the birth of their infant. Maternal measures included diet, stress, current mental and physical health, health history, and lifestyle. In addition, maternal biological samples (DNA, blood, urine, and spot breast milk samples) were banked. Paternal data included current mental and physical health, health history, lifestyle, and banked DNA samples. For infants, DNA and blood were collected as well as information on health, development and feeding behavior. Results At the end of recruitment in 2012, the APrON cohort included 2140 women, 2172 infants, and 1417 biological fathers. Descriptive statistics of the cohort, and comparison of women who stayed in the study and those who dropped out are discussed. Conclusion Findings from the longitudinal cohort may have important implications for health policy and clinical practice.

Background Small Canadian rural maternity services are struggling to maintain core staffing and remain open. Existing evidence states that having to travel to access maternity services is associated with adverse outcomes. The goal of this study is to systematically examine rural maternal and newborn outcomes across three Canadian provinces. Methods We analyzed maternal newborn outcomes data through provincial perinatal registries in British Columbia, Alberta and Nova Scotia for deliveries that occurred between April 1st 2003 and March 31st 2008. All births were allocated to maternity service catchments based on the residence of the mothers. Individual catchments were stratified to service levels based on distance to access intrapartum maternity services or the model of maternity services available in the community. The amalgamation of analyses from each jurisdiction involved comparison of logistic regression effect estimates. Results The number of singleton births included in the study is 150,797. Perinatal mortality is highest in communities that are greater than 4 h from maternity services overall. Rates of prematurity at less than 37 weeks gestation are higher for rural women without local access to services. Caesarean section rates are highest in communities served by general surgical models. Conclusion Composite analysis of data from three Canadian provinces provides the strongest evidence to date demonstrating that we need to sustain small community maternity services with and without caesarean section capability.

The enduring pandemic threat of Avian influenza A/H5N1 was underscored in January 2014 when the first North American H5N1 death was documented in a Canadian who returned from China [1, 2]. For almost 2 decades preceding this fatality, the pandemic potential of avian H5N1 influenza has been of concern [3, 4]. More than 30 sporadic cases of H5N1 infection occurred in 2013, for a total of 648 laboratory-confirmed illnesses, and ∼60% mortality was reported to the World Health Organization by 16 countries from 2003 to 2013 [5]. The repeated outbreaks of novel and variant avian and swine influenza viruses in humans have led to efforts to produce vaccines against these pandemic or potential pandemic viruses. Clinical trials of candidate H5N1 vaccines revealed that these hemagglutinins (HAs) were poor vaccine antigens [6–8], but antibody responses could be improved substantially with adjuvants [9]. Because vaccine supplies may be limited, it is also important to lower the antigen dose required to induce protection in order to make limited vaccine supplies available for protection of more people. For stockpiled vaccine antigens that require an adjuvant to achieve protective antibody titers, 1 rapid response approach would be to match the relevant antigen to a stockpiled adjuvant at pandemic onset and mix the reagents at designated field sites—the mix-and-match approach tested here. The squalene-containing oil-in-water emulsion adjuvant, MF59, improved the antibody response, permitted dose sparing, and enhanced efficacy [10] when paired with inactivated influenza vaccines [11–14]. MF59-adjuvanted seasonal influenza vaccines were first licensed for the elderly [15] by the European Union in 1997 and—along with MF59-adjuvanted 2009 H1N1 pandemic vaccines—have subsequently been licensed in more than 30 countries with an excellent safety profile and over 65 million doses delivered [16]. MF59-adjuvanted vaccines have not been licensed in the United States. However, the US Department of Health and Human Services (HHS) Biomedical Advanced Research and Development Authority (BARDA) has procured in the National Pre-pandemic Influenza Vaccine Stockpile both H5N1 vaccines and the oil-in-water adjuvants MF59 and AS03. Here, we studied a mix-and-match tactic that paired a stockpiled H5N1 antigen from one manufacturer with stockpiled MF59 adjuvant from another manufacturer, and we demonstrated the potential of point-of-use mixing as a flexile logistical tactic for rapid deployment of stockpiled vaccine reagents should an H5N1 pandemic occur.

The purpose of this review is to examine the role of nutrition in perinatal depression. Perinatal (maternal) depression refers to major and minor episodes during pregnancy (termed antenatal) and/or within the first 12 months after delivery (termed postpartum or postnatal). Prevalence of antenatal depression can be as high as 20%, while approximately 12% to 16% of women experience postpartum depression. These are probably conservative estimates, as cases of maternal depression are underreported or underdiagnosed. Risk factors for depression include genetic predisposition and environmental factors, as well as a number of social, psychological, and biological factors. One biological factor given increasing consideration is inadequate nutrition. Credible links between nutrient deficiency and mood have been reported for folate, vitamin B-12, calcium, iron, selenium, zinc, and n-3 fatty acids. For maternal depression, the nutrient that has received the most attention from nutrition researchers has been the n-3 essential fatty acids. Numerous studies, such as randomized controlled trials, cohort studies, and ecological studies, have found a positive association between low n-3 levels and a higher incidence of maternal depression. In addition, nutrient inadequacies in pregnant women who consume a typical western diet might be much more common than researchers and clinicians realize. A number of studies have reported inadequate intakes of n-3, folate, B vitamins, iron, and calcium in pregnant women. Depletion of nutrient reserves throughout pregnancy can increase a woman's risk for maternal depression.

This cross-sectional study assessed the sociodemographic characteristics of families whose children used naturopathic medicine, the reasons for use, and whether naturopathic and conventional medicine were combined in treating children's conditions. Data were collected in British Columbia, Alberta and Ontario, Canada. Ninety-eight completed questionnaires were analyzed. The results showed that participants (parents) were most likely to be females, university educated, had household income >$60,000, and also saw a naturopathic doctor for themselves. The most common conditions for which children saw a naturopathic doctor included allergies, digestive problems and skin problems, and the most important reasons for use included using all possible options and having a more holistic approach to care. Most parents reported combining naturopathic and conventional care for their children. Study limitations, in particular, selection bias, were discussed.

A major difficulty in treating cancer is the inability to differentiate between normal and tumor cells. The immune system differentiates tumor from normal cells by T cell receptor (TCR) binding of tumor-associated peptides bound to Major Histocompatibility Complex (pMHC) molecules. The peptides, derived from the tumor-specific proteins, are presented by MHC proteins, which then serve as cancer markers. The TCR is a difficult protein to use as a recombinant protein because of production issues and has poor affinity for pMHC; therefore, it is not a good choice for use as a tumor identifier outside of the immune system. We constructed a synthetic antibody-fragment (Fab) library in the phage-display format and isolated antibody-fragments that bind pMHC with high affinity and specificity. One Fab, fE75, recognizes our model cancer marker, the Human Epidermal growth factor Receptor 2 (HER2/neu) peptide, E75, bound to the MHC called Human Leukocyte Antigen-A2 (HLA-A2), with nanomolar affinity. The fE75 bound selectively to E75/HLA-A2 positive cancer cell lines in vitro. The fE75 Fab conjugated with (64)Cu selectively accumulated in E75/HLA-A2 positive tumors and not in E75/HLA-A2 negative tumors in an HLA-A2 transgenic mouse as probed using positron emission tomography/computed tomography (PET/CT) imaging. Considering that hundreds to thousands of different peptides bound to HLA-A2 are present on the surface of each cell, the fact that fE75 arrives at the tumor at all shows extraordinary specificity. These antibody fragments have great potential for diagnosis and targeted drug delivery in cancer.