Session 2: Personalised nutrition. Metabolomic applications in nutritional research

Metabolomics aims to profile all small molecules that are present in biological samples such as biofluids, tissue extracts and culture media. Combining the data obtained with multivariate data analysis tools allows the exploration of changes induced by a biological treatment or changes resulting from phenotype. Recently, there has been a large increase in interest in using metabolomics in nutritional research and because of the intimate relationship between nutrients and metabolism there exists great potential for the use of metabolomics within nutritional research. However, for metabolomics to reach its full potential within this field it is also important to be realistic about the challenges that are faced. Examples of such challenges include the necessity to have a clear understanding of the causes of variation in human metabolomic profiles, the effects of the gut microflora on the metabolomic profile and the interaction of the gut microflora with the host's metabolism. A further challenge that is particularly relevant for human nutritional research is the difficulty associated with biological interpretation of the data. Notwithstanding these and other challenges, several examples of successful applications to nutritional research exist. The link between the human metabolic phenotype, as characterised by metabolomic profiles, and dietary preferences proposes the potential role of metabolomics in personalised nutrition.     

The use of clinical profiles in the investigation of foodborne outbreaks in restaurants: United States, 1982-1997

Improving the efficiency of outbreak investigation in restaurants is critical to reducing outbreak-associated illness and improving prevention strategies. Because clinical characteristics of outbreaks are usually available before results of laboratory testing, we examined their use for determining contributing factors in outbreaks caused by restaurants. All confirmed foodborne outbreaks reported to the Centers for Disease Control and Prevention (CDC) from 1982 to 1997 were reviewed. Clinical profiles were developed based on outbreak characteristics. We compared the percentage of contributing factors by known agent and clinical profile to their occurrence in outbreaks of unclassified aetiology. In total, 2246 foodborne outbreaks were included: 697 (31%) with known aetiology and 1549 (69%) with aetiology undetermined. Salmonella accounted for 65% of outbreaks with a known aetiology. Norovirus-like clinical profiles were noted in 54% of outbreaks with undetermined aetiology. Improper holding times and temperatures were associated with outbreaks caused by Clostridium perfringens, Bacillus cereus, Staphylococcus aureus, and Salmonella, and also with outbreaks of undetermined aetiology that fitted diarrhoea-toxin and vomiting-toxin clinical profiles. Poor personal hygiene was associated with norovirus, Shigella, and Salmonella, and also with outbreaks that fitted norovirus-like and vomiting-toxin clinical profiles. Contributing factors were similar for outbreaks with known aetiology and for those where aetiology was assigned by corresponding clinical profile. Rapidly categorizing outbreaks by clinical profile, before results of laboratory testing are available, can help identification of factors which contributed to the occurrence of the outbreak and will promote timely and efficient outbreak investigations.     

Influence of migrants on regional variations of stomach and colon cancer mortality in the Western United States.

In order to examine the impact of migrants on regional variations in stomach and colon cancer, standardized mortality ratios (SMRs) were calculated for the total, nonmigrant (born and dying in same state), and migrant (born out of state) White residents of each of the 11 western states in the United States (US). The SMRs were derived from the National Center for Health Statistics' Mortality Detail Files for 1979-1981 and the 1980 Census Public Use Microdata 5-Percent Sample tapes. Migrants in the western US accounted for 79% of all stomach and colon cancer deaths. There was no consistent relationship between the SMRs of migrants and nonmigrants, with the migrant SMRs being higher in some states and lower in others. As a consequence of this differential impact, and their substantial numbers, migrants obscured the underlying regional patterns of mortality risk observed in the nonmigrants. The states of high or low risk were more contiguous in the analysis based on nonmigrants than the total population, and the interstate ranges in mortality were greater for nonmigrants. In areas with high in-migration, mortality atlases based on the total population may give an inaccurate portrayal of regional mortality risks, and spurious correlations may arise between the distributions of diseases and environmental characteristics of the regions. Regional mortality patterns of nonmigrants may more precisely reflect the factors which are influencing these cancers and thus provide a greater potential in providing clues to their aetiologies.     

Qualitative Study of Latino Cancer Patient Perspectives on Care Access and Continuity in a Rural,U.S.-Mexico Border Region

Access to quality cancer care for cancer patients living in the rural U.S.-Mexico border region is complex due to common binational health care-seeking behaviors and regional socio-economic and cultural characteristics. But little is known about the challenges border dwelling residents face when navigating their cancer care systems. In-depth interviews were conducted with 22 cancer patients in Southern California. Thematic analysis was applied to identify patterns of meaning in the data. Emerging themes were: (1) delays in cancer care coordination: (a) poor coordination of cancer care (b) U.S. and cross-border discordance in cancer diagnosis; (2) regional shortage of cancer specialists; and (3) financial hardship. Findings revealed that care needs distinctly involved care coordination in/outside of the patient’s community and bi-national care coordination. In addition to local solutions to improve cancer coordination through community-based partnerships, efforts to bridge care in a two-nation context are also imperative.     

Characterization of an orthovoltage biological irradiator used for radiobiological research

Orthovoltage irradiators are routinely used to irradiate specimens and small animals in biological research. There are several reports on the characteristics of these units for small field irradiations. However, there is limited knowledge about use of these units for large fields, which are essential for emerging large-field irregular shape irradiations, namely total marrow irradiation used as a conditioning regimen for hematological malignancies. This work describes characterization of a self-contained Orthovoltage biological irradiator for large fields using measurements and Monte Carlo simulations that could be used to compute the dose for in vivo or in vitro studies for large-field irradiation using this or a similar unit. Percentage depth dose, profiles, scatter factors, and half-value layers were measured and analyzed. A Monte Carlo model of the unit was created and used to generate depth dose and profiles, as well as scatter factors. An ion chamber array was also used for profile measurements of flatness and symmetry. The output was determined according to AAPM Task Group 61 guidelines. The depth dose measurements compare well with published data for similar beams. The Monte Carlo–generated depth dose and profiles match our measured doses to within 2%. Scatter factor measurements indicate gradual variation of these factors with field size. Dose rate measured by placing the ion chamber atop the unit''s steel plate or solid water indicate enhanced readings of 5 to 28% compared with those measured in air. The stability of output over a 5-year period is within 2% of the 5-year average.     

Profiles of Met and Unmet Needs in People with Dementia According to Caregivers’ Perspective: Results from a European Multicenter Study

ObjectivesThis exploratory study aimed at investigating profiles of care needs in people with mild to moderate dementia and examined variables associated with these profiles.DesignA longitudinal international cohort study.Setting and ParticipantsThe baseline data of 447 community-dwelling dyads of people with dementia and their caregivers from the Access to Timely Formal Care (Actifcare) Study were included for analysis.MethodsA latent class analysis was applied to identify profiles of needs, measured with the Camberwell Assessment of Need for the Elderly as rated by the caregiver. We examined sociodemographic (eg, relative stress scale) and clinical characteristics (eg, neuropsychiatric inventory) associated with these profiles.ResultsFour distinct need profiles were identified through latent class analysis. These comprised a “no need” profile (41% of the sample), a “met psychological needs” profile (25%), a “met social needs” profile (19%), and an “unmet social needs” profile (15%). A larger impact of caregiving on the caregiver's life as indicated by a higher relative stress scale score was associated with the “unmet social needs” profile.Conclusions and ImplicationsIn this large European sample, there was a subgroup of persons with dementia with high “unmet social needs” whose caregivers simultaneously perceived high stress in their caregiving tasks. Identification of these profiles may help provision of appropriate support for these people.     

Strengthening the System: Joint Commission Standards and Building on what We Know

The authors present a methodology that measures improvement in customer satisfaction scores when those scores are already high and the production process is slow and thus does not generate a large amount of useful data in any given time period. The authors used these techniques with data from a midsized rehabilitation institute affiliated with a regional, nonprofit medical center. Thus, this article functions as a case study, the findings of which may be applicable to a large number of other healthcare providers that share both the mission and challenges faced by this facility. The methodology focused on 2 factors: use of the unique characteristics of panel data to overcome the paucity of observations and a dynamic benchmarking approach to track process variability over time. By focusing on these factors, the authors identify some additional areas for process improvement despite the institute's past operational success.     

Epidemiology of HIV and sexually transmitted infections in China

As the most populous country in the world, China has been confronted with the huge challenges that HIV and sexually transmitted infections pose. The HIV infection rate among adults is lower than 0.1%, however, the estimated number of HIV infections sits around one million, according to the estimation of some experts. HIV infection is highly prevalent in some regional areas of China and the incidence rate of sexually transmitted infections has sharply increased since the 1980s. The number of HIV infections may reach 10 million if no effective measures are taken. This article aims to outline the profile of the epidemic in China as well as to elaborate on the contributing factors and the response of the government and community.     

Why Do Patients with Inflammatory Arthritis Often Score States “Worse than Death” on the EQ-5D? An Investigation of the EQ-5D Classification System

Objective:  Using inflammatory arthritis patients as an example, we investigate EuroQol-5D (EQ-5D) profiles resulting in states worse than death (WTD), and the heath status of patients occupying these states.
Methods:  Baseline data from two UK trials were used that reflected the range of arthritis states/severity found in routine practice. EQ-5D profiles resulting in negative valuations (i.e., states WTD) based on UK weights were identified. EQ-5D scores for these profiles from alternative valuation sets, including a reanalysis of the UK weights, were compared. The health status and characteristics of patients, and factors associated with patients in the low distribution of the EQ-5D and those with WTD EQ-5D scores were identified.
Results:  Seven hundred patients were included in the analysis. Sixty-two (9%) patients occupied states WTD. Patients occupied 9 of the possible 84health profiles with negative scores (53% occupied one profile); this profile was not rated WTD by any of the alternative EQ-5D scoring algorithms. All WTD profiles included severe pain/discomfort plus moderate problems in ≥3 other domains. Patients with WTD valuations reported higher levels of pain, and feeling downhearted and low on alternative health status measures.
Conclusions:  Pain was the predominant factor in the WTD EQ-5D profiles occupied by arthritis patients. Patients occupying states WTD have poorer health-related quality of life than patients in low "better than death" states. Valuations of profiles vary according to how sets of preference weights for health profiles were developed. Further research should explore whether WTD valuations are supported by qualitative evidence and reflect the patient's health and experience of disease.     

A conceptual and methodological framework for investigating etiologic heterogeneity

Cancer has traditionally been studied using the disease site of origin as the organizing framework. However, recent advances in molecular genetics have begun to challenge this taxonomy, as detailed molecular profiling of tumors has led to discoveries of subsets of tumors that have profiles that possess distinct clinical and biological characteristics. This is increasingly leading to research that seeks to investigate whether these subtypes of tumors have distinct etiologies. However, research in this field has been opportunistic and anecdotal, typically involving the comparison of distributions of individual risk factors between tumors classified on the basis of candidate tumor characteristics. The purpose of this article is to place this area of investigation within a more general conceptual and analytic framework, with a view to providing more efficient and practical strategies for designing and analyzing epidemiologic studies to investigate etiologic heterogeneity. We propose a formal definition of etiologic heterogeneity and show how classifications of tumor subtypes with larger etiologic heterogeneities inevitably possess greater disease risk predictability overall. We outline analytic strategies for estimating the degree of etiologic heterogeneity among a set of subtypes and for choosing subtypes that optimize the heterogeneity, and we discuss technical challenges that require further methodologic research. We illustrate the ideas by using a pooled case‐control study of breast cancer classified by expression patterns of genes known to define distinct tumor subtypes. Copyright © 2013 John Wiley & Sons, Ltd.     

A regional profile of suicide in Queensland

Abstract: A regional profile of suicide in Queensland follows on from earlier work which failed to find urban–rural differences in suicide rates. Suicide rates were higher in the north of the state and lower in the more developed south. Rural Queensland health regions displayed both the lowest (Darling Downs and Mackay) and the highest (Peninsula) suicide rates. Socioeconomic factors correlated with these differences in some regions. Suicide rates for Aboriginal and Torres Strait Islanders, especially the young, were high, and may have contributed to elevated suicide rates in northern Queensland, but the numbers were insufficient to account for observed differences.     

Understanding the metabolome – challenges for metabolomics

Metabolomics is a comprehensive method for metabolite assessment, measuring the overall metabolic signature of biological samples. This approach opens up many possibilities in areas such as new biomarker discovery and hypothesis generation. The application of metabolomics is growing rapidly but many challenges must first be addressed before it can reach its true potential. Metabolomics organisations are currently working towards guidelines for commonality in metabolomics experiments as development of optimal methodologies and study designs are needed. Blood and urine appear to be the most useful biofluids for nutrition research, but an array of biofluids, cells and tissues can be used. The key steps required for the successful understanding of metabolomics data are compound identification and biological interpretation. Many databases of compounds are available but are still under construction with much information remaining to be populated. An understanding of the effects of normal physiological variation on metabolic profiles is essential for accurate interpretation of profile changes, particularly in human studies, because of diversity in lifestyle and environmental factors. The effects of factors such as ethnicity, gender, age, body composition, health, dietary intake, physical activity, gut microflora and stress need to be further explored in order to advance the understanding of the human metabolome and therefore improve data interpretation.     

Potential for recognition of airborne asbestos fibres from spatial laser scattering profiles

This Short Communication describes some preliminary results of research which seeks to develop a method by which individual airborne asbestos fibres may be detected in real-time within a contaminated environment. The method proposes using an analysis of the spatial laser scattering profile (i.e. the complex manner in which individual particles scatter laser light), recorded from individual airborne particles, as a means of classifying the particles in terms of their morphological characteristics. Scattering profiles have been recorded from both crocidolite and chrysotile fibres and these display differentiating features which suggest that in certain cases it may be possible to discriminate each type of fibre from other airborne particulates. Examples of scattering profiles are presented and methods of automated pattern recognition, which are currently under development, are briefly discussed.     

Challenges of citizen participation in regional health authorities

Citizen participation has been included as part of health reform, often in the form of lay health authorities. In Canada, these authorities are variously known as regional health boards or councils. A set of challenges is associated with citizen participation in regional health authorities. These challenges relate to: differences in opinion about whether there should be citizen participation at all; differences in perception of the levels and processes of participation; differences in opinion with respect to the roles and responsibilities of health authority members; differences in opinion about the appropriate composition of the authorities; differences in opinion about the requisite skills and attributes of health authority members; having a good support base (staff, good information, board development); understanding and operationalizing various roles of the board (governance and policy setting) versus the board staff (management and administration); difficulties in ensuring the accountability of the health authorities; and measuring the results of the work and decisions of the health authorities. Despite these challenges, regional health authorities are gaining support as both theoretically sound and pragmatically based approaches to health-system reform. This review of the above challenges suggests that each of the concerns remains a significant threat to meaningful public participation.     

Cancer registries: their interest and practical problems

Cancer registries record all new cases of cancer within the population they survey. Thus they provide accurate regional measurements of cancer morbidity and mortality and their geographical distribution. This form of epidemiology allows the study of regional variations and alterations with the passage of time. It also allows the study of environmental factors that might cause cancer. The work of the French regional cancer registries is described to illustrate these points. The problems of running a cancer registry are also set out and suggestions are made for future organization. The statistics gathered by such registries indicate possible methods for the early detection and treatment of some cancers and provide evidence of the long-term effects of all kinds of therapy. The socio-economic aspects of cancer can also be measured by the registry, thus providing valuable data for use in the planning of health care in any community.     

A Socio-cultural Perspective on Cancer Control Issues for Asian Americans

PURPOSE: Eighty­five to ninety percent of cancer incidence is attributable to lifestyle choices, such as diet, life habits such as smoking, and environmental factors. Culture is the single force most influential on lifestyles. This paper provides a framework to understand the potential contribution of sociocultural factors to cancer control. METHODS: This literature review of culture and cancer control provides a perspective on Asian American populations. Culture is defined in a manner that enables researchers and practitioners to begin to focus on the fundamental elements of culture that directly influence health behavior. FINDINGS: Only four studies were found that address sociocultural factors in cancer control for Asian Americans. Each of these studies found significant variations in the response to cancer than Euro­American populations. Only mainstream researchers or practitioners, who are knowledgeable enough about Asian American cultures to be sensitive to these differences, would recognize these variations. CONCLUSIONS: The widening disparities in cancer outcomes between Asian- and Euro­Americans challenges the current research and practice paradigms for cancer control. A Cultural Systems Approach would strengthen future studies. This paradigm requires multi­level analyses of individuals and populations within specific contexts in order to identify culturally based strategies to improve practice along the cancer care continuum.     

Environmental pollutants and breast cancer

Breast cancer is the most common cancer in women and the leading cause of cancer death among women 35-54 years of age. Rising incidence, increased risk among migrants to higher risk regions, and poor prediction of individual risk have prompted a search for additional modifiable factors. Risk factors for breast cancer include reproductive characteristics associated with estrogen and other hormones, pharmaceutical hormones, and activities such as alcohol use and lack of exercise that affect hormone levels. As a result, investigation of hormonally active compounds in commercial products and pollution is a priority. Compounds that cause mammary tumors in animals are additional priorities. Animal models provide insight into possible mechanisms for effects of environmental pollutants on breast cancer and identify chemical exposures to target in epidemiologic studies. Although few epidemiologic studies have been conducted for chemical exposures, occupational studies show associations between breast cancer and exposure to certain organic solvents and polycyclic aromatic hydrocarbons (PAHs). Population-based studies have been limited to a few organochlorine compounds and PAHs and have been mostly negative. A variety of challenges in studies of breast cancer and the environment may have contributed to negative findings. Lack of exposure assessment tools and few hypothesis-generating toxicologic studies limit the scope of epidemiologic studies. Issues of timing with respect to latency and periods of breast vulnerability, and individual differences in susceptibility pose other challenges. Substantial work is needed in exposure assessment, toxicology, and susceptibility before we can expect a pay-off from large epidemiologic studies of breast cancer and environment.     

Examining health-related quality of life patterns in women with breast cancer

Purpose

We aimed to identify subgroups of women with breast cancer who experience different health-related quality of life (HRQOL) patterns during active treatment and survivorship and determine characteristics associated with subgroup membership.

Methods

We used data from the third phase of the population-based Carolina Breast Cancer Study and included 2142 women diagnosed with breast cancer from 2008 to 2013. HRQOL was measured, on average, 5 and 25 months post diagnosis. Latent profile analysis was used to identify HRQOL latent profiles (LPs) at each time point. Latent transition analysis was used to determine probabilities of women transitioning profiles from 5 to 25 months. Multinomial logit models estimated adjusted odds ratios (aORs) and 95% confidence intervals for associations between patient characteristics and LP membership at each time point.

Results

We identified four HRQOL LPs at 5 and 25 months. LP1 had the poorest HRQOL and LP4 the best. Membership in the poorest profile at 5 months was associated with younger age aOR 0.95; 0.93–0.96, White race aOR 1.48; 1.25–1.65, being unmarried aOR 1.50; 1.28–1.65 and having public aOR 3.09; 1.96–4.83 or no insurance aOR 6.51; 2.12–20.10. At 25 months, Black race aOR 1.75; 1.18–1.82 was associated with the poorest profile membership. Black race and smoking were predictors of deteriorating to a worse profile from 5 to 25 months.

Conclusions

Our results suggest patient-level characteristics including age at diagnosis and race may identify women at risk for experiencing poor HRQOL patterns. If women are identified and offered targeted HRQOL support, we may see improvements in long-term HRQOL and better breast cancer outcomes.

     

Comparison of appropriateness of cholesterol testing in general practice with the recommendations of national guidelines: an audit of patient records in 20 general practices.

OBJECTIVE: To compare the profiles of those patients selected by general practitioners for measurement of serum cholesterol with the recommended profiles for opportunistic cholesterol testing described in the national practice guidelines published by the Dutch College of General Practitioners. DESIGN: Retrospective audit of general practitioners' records. MATERIALS: Practice records of 3577 adult patients systematically sampled from 20 general practices. MAIN MEASURES: With criteria set by the national guidelines, the proportion of patients per practice (a) for whom cholesterol testing would be considered justified, and (b) for whom cholesterol testing would be considered unjustified, and the proportion of patients within each of these groups who had had a cholesterol measurement recorded. RESULTS: Cholesterol tests were performed on 415 (11.7%) of the 3577 patients. National guidelines on the management of hypercholesterolaemia state that a positive cardiovascular risk profile is an indication for cholesterol measurement. Just under one fifth (668) of the patients in this study were recorded as having a positive cardiovascular risk profile, but only 31% of these had had their cholesterol measured. Of the patients without recorded evidence of a positive cardiovascular risk profile cholesterol had been measured in 8%. Restricting the analyses to the age group 18-65 (n = 3060) of whom 12.5% had a positive risk profile, did not improve the results. In practices with a computerised information system 37% of patients with recorded evidence of a positive cardiovascular risk profile had had their cholesterol measured. CONCLUSIONS: Cholesterol testing was not targeted as selectively as recommended by the national guidelines. The major problem was failure to test those likely to benefit. Improving the targeting of cholesterol measurements would undoubtedly increase the workload of general practitioners. If the national guidelines are to have an effect on health promotion the first step must be to increase the proportion of patients with positive cardiovascular risk profiles who get their cholesterol tested. A major factor in successfully selecting cases seems to be that practices are equipped with a computerised medical information system.