Precision subclassification of type 2 diabetes: a systematic review.

BACKGROUND: Heterogeneity in type 2 diabetes presentation and progression suggests that precision medicine interventions could improve clinical outcomes. We undertook a systematic review to determine whether strategies to subclassify type 2 diabetes were associated with high quality evidence, reproducible results and improved outcomes for patients. METHODS: We searched PubMed and Embase for publications that used 'simple subclassification' approaches using simple categorisation of clinical characteristics, or 'complex subclassification' approaches which used machine learning or 'omics approaches in people with established type 2 diabetes. We excluded other diabetes subtypes and those predicting incident type 2 diabetes. We assessed quality, reproducibility and clinical relevance of extracted full-text articles and qualitatively synthesised a summary of subclassification approaches. RESULTS: Here we show data from 51 studies that demonstrate many simple stratification approaches, but none have been replicated and many are not associated with meaningful clinical outcomes. Complex stratification was reviewed in 62 studies and produced reproducible subtypes of type 2 diabetes that are associated with outcomes. Both approaches require a higher grade of evidence but support the premise that type 2 diabetes can be subclassified into clinically meaningful subtypes. CONCLUSION: Critical next steps toward clinical implementation are to test whether subtypes exist in more diverse ancestries and whether tailoring interventions to subtypes will improve outcomes.

In people with type 2 diabetes there may be differences in the way people present, including for example, their symptoms, body weight or how much insulin they make. We looked at recent publications describing research in this area to see whether it is possible to separate people with type 2 diabetes into different subgroups and, if so, whether these groupings were useful for patients. We found that it is possible to group people with type 2 diabetes into different subgroups and being in one subgroup can be more strongly linked to the likelihood of developing complications over others. This might mean that in the future we can treat people in different subgroups differently in ways that improves their treatment and their health but it requires further study.

Second international consensus report on gaps and opportunities for the clinical translation of precision diabetes medicine.

Precision medicine is part of the logical evolution of contemporary evidence-based medicine that seeks to reduce errors and optimize outcomes when making medical decisions and health recommendations. Diabetes affects hundreds of millions of people worldwide, many of whom will develop life-threatening complications and die prematurely. Precision medicine can potentially address this enormous problem by accounting for heterogeneity in the etiology, clinical presentation and pathogenesis of common forms of diabetes and risks of complications. This second international consensus report on precision diabetes medicine summarizes the findings from a systematic evidence review across the key pillars of precision medicine (prevention, diagnosis, treatment, prognosis) in four recognized forms of diabetes (monogenic, gestational, type 1, type 2). These reviews address key questions about the translation of precision medicine research into practice. Although not complete, owing to the vast literature on this topic, they revealed opportunities for the immediate or near-term clinical implementation of precision diabetes medicine; furthermore, we expose important gaps in knowledge, focusing on the need to obtain new clinically relevant evidence. Gaps include the need for common standards for clinical readiness, including consideration of cost-effectiveness, health equity, predictive accuracy, liability and accessibility. Key milestones are outlined for the broad clinical implementation of precision diabetes medicine.

Systematic review of precision subclassification of type 2 diabetes.

Heterogeneity in type 2 diabetes presentation, progression and treatment has the potential for precision medicine interventions that can enhance care and outcomes for affected individuals. We undertook a systematic review to ascertain whether strategies to subclassify type 2 diabetes are associated with improved clinical outcomes, show reproducibility and have high quality evidence. We reviewed publications that deployed 'simple subclassification' using clinical features, biomarkers, imaging or other routinely available parameters or 'complex subclassification' approaches that used machine learning and/or genomic data. We found that simple stratification approaches, for example, stratification based on age, body mass index or lipid profiles, had been widely used, but no strategy had been replicated and many lacked association with meaningful outcomes. Complex stratification using clustering of simple clinical data with and without genetic data did show reproducible subtypes of diabetes that had been associated with outcomes such as cardiovascular disease and/or mortality. Both approaches require a higher grade of evidence but support the premise that type 2 diabetes can be subclassified into meaningful groups. More studies are needed to test these subclassifications in more diverse ancestries and prove that they are amenable to interventions.

Rapid and Efficient Analysis of Microcystins, Nodularin, Cylindrospermopsin, and Anatoxin-a in Drinking Water by LC Tandem MS.

A fast and sensitive LC-MS method was developed for the simultaneous analysis of 11 cyanotoxins in drinking water. The toxins in this method included eight microcystins, as well as nodularin, anatoxin-a, and cylindrospermopsin. Sample processing involved a small sample volume and a direct dilution procedure that could be performed in minutes rather than hours using traditional SPE procedures. This method also featured a short acquisition time of 12 min with an adequate separation of all analytes. Validation results demonstrated good sensitivity with LODs <100 ng/L and good precision (RSD < 20%) and accuracy. Analyte stability was also thoroughly studied. The matrix effect was minimal, and tap water used for calibrators and controls. No sample carryover was observed after the highest concentration calibrator.

Opiorphin analysis in equine plasma and urine using hydrophilic interaction LC-MS.

BACKGROUND: Due to opiorphin's analgesic and antidepressant functions, its illicit use is rumored in some racing jurisdictions. Opiorphin is very difficult to detect due to its hydrophilic nature and rapid degradation in plasma and urine samples. METHODOLOGY & RESULTS: We have developed a sensitive, reliable method for opiorphin detection and confirmation in equine samples, using EDTA to inhibit analyte degradation between the time of collection and analysis. Opiorphin was extracted by weak cation exchange followed by analysis using HILIC-MS/MS. The method was validated and the LOD was determined to be 50 pg/ml in equine plasma and urine. CONCLUSION: The method has good selectivity and precision and is the first reported method for the detection of opiorphin in equine plasma and urine.

Fast and sensitive analysis of dermorphin and HYP6-dermorphin in equine plasma using liquid chromatography tandem mass spectrometry.

Dermorphin and HYP(6) -dermorphin are hepta-peptides and natural opioids originally isolated from the skin of South American frogs. They are more potent than morphine but less likely to produce drug tolerance and addiction. These properties make them ideal candidates for the doping of racehorses to enhance performance during competition. Dermorphin was recently classified as a Class I drug by Racing Commissioners International (RCI), indicating that it is a banned substance in equine athletes. To enforce this ban, a fast and sensitive method was developed for dermorphin and HYP(6)-dermorphin analysis in equine plasma. Equine plasma (2 ml) was extracted on a mixed mode cation exchange solid-phase column. After extraction, dermorphin and HYP(6)-dermorphin were separated and detected using a liquid chromatography (LC) triple quadrupole linear ion trap mass spectrometry in positive multiple-reaction-monitoring (MRM) mode. Each analysis was 3.5 min. Four MRM transitions were used for identification of each compound. The extraction procedure was efficient and the limits of detection (LOD) were 2 pg/ml and 10 pg/ml for dermorphin and HYP(6)-dermorphin, respectively. The method has good selectivity and precision. Results of stability studies showed that both analytes were stable at low temperature. This is the first report of dermorphin and HYP(6)-dermorphin analysis in equine plasma, which could be adopted as a regular screening or confirmation method for controlling the abuse of these compounds in equine sports.

Tobacco crop substitution: pilot effort in China.

In China, approximately 20 million farmers produce the world's largest share of tobacco. Showing that income from crop substitution can exceed that from tobacco growth is essential to persuading farm families to stop planting tobacco, grown abundantly in Yunnan Province. In the Yuxi Municipality, collaborators from the Yuxi Bureau of Agriculture and the University of California at Los Angeles School of Public Health initiated a tobacco crop substitution project. At 3 sites, 458 farm families volunteered to participate in a new, for-profit cooperative model. This project successfully identified an approach engaging farmers in cooperatives to substitute food crops for tobacco, thereby increasing farmers' annual income between 21% and 110% per acre.

Rapid and sensitive analysis of 3,4-methylenedioxypyrovalerone in equine plasma using liquid chromatography-tandem mass spectrometry.

3,4-Methylenedioxypyrovalerone (MDPV) is a psychoactive drug with potent stimulant properties and potential for abuse and drug dependency. MDPV was recently classified as a Class I drug by Racing Commissioners International, indicating that it is a banned substance in equine athletes because it lacks therapeutic value in horses. To enforce this ban, a sensitive and fast liquid chromatography-tandem mass spectrometry method was needed. It is for this reason that this method was developed for quantification and confirmation of MDPV in equine plasma. Sample preparation involved liquid-liquid extraction. The analyte was analyzed by a triple-quadrupole linear ion trap mass spectrometer in positive multiple-reaction-monitoring and enhanced product ion scan modes. The method was validated for precision, accuracy, limit of detection (LOD), limit of quantification (LOQ), linearity, stability, extraction recovery, matrix effect, dilution accuracy and selectivity. The extraction recovery was >90%. The linearity range was from 5 to 15,000 pg/mL. LOD and LOQ were 2 and 5 pg/mL, respectively. Intra-day and inter-day accuracies were nearly 100%. The method is suitable for screening, quantification and confirmation of MDPV in equine plasma and has been successfully used to detect and confirm the presence of MDPV in equine plasma obtained post-competition.

Social, economic, and political processes that create built environment inequities: perspectives from urban African Americans in Atlanta.

Growing evidence suggests that the built environment features found in many high-poverty urban areas contribute to negative health outcomes. Both built environment hazards and negative health outcomes disproportionately affect poor people of color. We used community-based participatory research and Photovoice in inner-city Atlanta to elicit African Americans' perspectives on their health priorities. The built environment emerged as a critical factor, impacting physical and mental health outcomes. We offer a conceptual model, informed by residents' perspectives, linking social, economic, and political processes to built environment and health inequities. Research, practice, and policy implications are discussed within an environmental justice framework.

Photovoice: use of a participatory action research method to explore the chronic pain experience in older adults.

Photovoice is a participatory action research method in which individuals photograph their everyday health and work realities. The objective of this study is to determine the efficacy of photovoice as a unique and innovative method examining the pain experiences of clinic and nonclinic-based Black and White adults older than 50 years of age. Participants took photographs and composed written narratives based on their experiences with pain. Respondents also completed several open-ended questions focusing on their daily experiences with chronic pain. Some respondents identified their participation as a way of helping others cope with pain. Others felt it was a way of sharing their experiences with others. Photovoice might be used as an alternative method to enhance the understanding of the pain experience, thereby allowing researchers, health care providers, and policy makers to understand more fully and identify the dimensions of the pain experience not captured through quantitative measures.

Breast self-examination among Chinese immigrant women.

The incidence of breast cancer is rising rapidly among the fast-growing demographic group of Asian American and Pacific Islanders (AAPIs). In this study, the authors assessed the awareness of breast self-exam (BSE) and factors predicting practice of BSE among Chinese immigrant women living in San Francisco. Three hundred and ninety-seven women participated in a telephone survey; 80.9% reported having heard of BSE but only 53.9% reported practice of BSE during the past year. Logistic regression modeling found that increased length of stay in the United States, higher income, socializing with more Chinese than non-Chinese, and a birthplace other than U.S. and Chinese communities predicted BSE practice. The findings indicate that although familiarity with BSE is high among this group of Chinese immigrant women, self-reported actual practice is far from optimal. This study points to the need for culturally appropriate interventions that will encourage and motivate immigrant Chinese women to practice BSE on a monthly basis.

Flint Photovoice: community building among youths, adults, and policymakers.

Flint Photovoice represents the work of 41 youths and adults recruited to use a participatory-action research approach to photographically document community assets and concerns, critically discuss the resulting images, and communicate with policymakers. At the suggestion of grassroots community leaders, we included policymakers among those asked to take photographs. In accordance with previously established photovoice methodology, we also recruited at the project's outset another group of policymakers and community leaders to provide political will and support for implementing photovoice participants' policy and program recommendations. Flint Photovoice enabled youths to express their concerns about neighborhood violence to policymakers and was instrumental in acquiring funding for local violence prevention. We note salutary outcomes produced by the inclusion of policymakers among adults who took photographs.

Family, maternal, and child health through photovoice.

OBJECTIVE: (1) To introduce photovoice, a participatory action research methodology, for use by MCH program managers to enhance community health assessments and program planning efforts, (2) to enable community people to use the photovoice methodology as a tool to record, reflect, and communicate their family, maternal, and child health assets and concerns, and (3) to educate community leaders about family, maternal, and child health issues from a grassroots perspective. METHODS: Photovoice is based upon the theoretical literature on education for critical consciousness, feminist theory, and community-based approaches to documentary photography. Picture This Photovoice project took place in Contra Costa, an economically and ethnically diverse county in the San Francisco Bay area. Sixty county residents of ages 13-50 participated in 3 sessions during which they received training from the local health department in the techniques and process of photovoice. Residents were provided with disposable cameras and were encouraged to take photographs reflecting their views on family, maternal, and child health assets and concerns in their community, and then participated in group discussions about their photographs. Community events were held to enable participants to educate MCH staff and community leaders. RESULTS: The photovoice project provided MCH staff with information to supplement existing quantitative perinatal data and contributed to an understanding of key MCH issues that participating community residents would like to see addressed. Participants' concerns centered on the need for safe places for children's recreation and for improvement in the broader community environment within county neighborhoods. Participants' definitions of family, maternal, and child health assets and concerns differed from those that MCH professionals may typically view as MCH issues (low birth weight, maternal mortality, teen pregnancy prevention), which helped MCH program staff to expand priorities and include residents' foremost concerns. CONCLUSIONS: MCH professionals can apply photovoice as an innovative participatory research methodology to engage community members in needs assessment, asset mapping, and program planning, and in reaching policy makers to advocate strategies promoting family, maternal, and child health as informed from a grassroots perspective.

Reproductive health indicators for China's rural areas.

We report community-based development of reproductive health indicators for China's rural areas. To generate these indicators, we sequenced two participatory techniques known as nominal group process and Delphi survey methodology. Nominal group process entailed grassroots reproductive health workers' generating indicators, followed by refinement and prioritization of these indicators through a consensus-building Delphi process among nationally and internationally known reproductive health experts. Major criteria for the indicators were practicality, feasibility, and measurability within China's rural areas. We explain the importance of establishing these indicators for application in rural China and other developing countries as a complement to the World Health Organization's reproductive health indicators for global monitoring; present the identified indicators; and describe lessons learned from field testing in low-, middle-, and high-income counties of China's countryside.