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The establishment of genomics in health care systems has been occurring for the past decade. It is recognised that implementing genomics within a health service is challenging without a system-wide approach. Globally, as clinical genomics implementation programs have matured there is a growing body of information around program design and outcomes. Program structures vary depending on local ecosystems including the health system, politics and funding availability, however, lessons from other programs are important to the design of programs in different jurisdictions. Here we describe an adaptive approach to the implementation of genomics into a publicly funded health care system servicing a population of 5.1 million people. The adaptive approach enabled flexibility to facilitate substantial changes during the program in response to learnings and external factors. We report the benefits and challenges experienced by the program, particularly in relation to the engagement of people and services, and the design of both individual projects and the program as a whole.

The complexities of the informed consent process for participating in research in genomic medicine are well-documented. Inspired by the potential for Dynamic Consent to increase participant choice and autonomy in decision-making, as well as the opportunities for ongoing participant engagement it affords, we wanted to trial Dynamic Consent and to do so developed our own web-based application (web app) called CTRL (control). This paper documents the design and development of CTRL, for use in the Australian Genomics study: a health services research project building evidence to inform the integration of genomic medicine into mainstream healthcare. Australian Genomics brought together a multi-disciplinary team to develop CTRL. The design and development process considered user experience; security and privacy; the application of international standards in data sharing; IT, operational and ethical issues. The CTRL tool is now being offered to participants in the study, who can use CTRL to keep personal and contact details up to date; make consent choices (including indicate preferences for return of results and future research use of biological samples, genomic and health data); follow their progress through the study; complete surveys, contact the researchers and access study news and information. While there are remaining challenges to implementing Dynamic Consent in genomic research, this study demonstrates the feasibility of building such a tool, and its ongoing use will provide evidence about the value of Dynamic Consent in large-scale genomic research programs.

In health and medical research, guidelines are a set of statements and recommendations, whereby experts or stakeholders assess published literature to generate practical advice for a specific audience. This emphasis on guidelines development with expert consultation and published literature is not practical or inclusive when working in disciplines with minimal data and addressing issues that concern under-represented communities. Here we describe the process used for developing guidelines for the conduct of genomic research projects in partnership with Aboriginal and Torres Strait Islander peoples. A new technology with individual and community level ethical and social implications, and First Nations peoples with cultural and community expectations for research. We developed the guidelines through a consultation process that used participatory action research to engage with various stakeholders during multiple rounds of tailored activities. The end product, ‘Genomic Partnerships: Guidelines for Genomics Research with Aboriginal and Torres Strait Islander peoples of Queensland’ reflects the needs of the end-users and perspectives of the Aboriginal and Torres Strait Islander peoples, communities and organisations that participated. Through this process, we have identified recommendations for developing guidelines with other under-represented communities.

Background There has been considerable investment and strategic planning to introduce genomic testing into Australia’s public health system. As more patients’ genomic data is being held by the public health system, there will be increased requests from researchers to access this data. It is important that public policy reflects public expectations for how genomic data that is generated from clinical tests is used. To inform public policy and discussions around genomic data sharing, we sought public opinions on using genomic data contained in medical records for research purposes in the Australian state of Queensland. Methods A total of 1494 participants completed an online questionnaire between February and May 2019. Participants were adults living in Australia. The questionnaire explored participant preferences for sharing genomic data or biological samples with researchers, and concerns about genomic data sharing. Results Most participants wanted to be given the choice to have their genomic data from medical records used in research. Their expectations on whether and how often they needed to be approached for permission on using their genomic data, depended on whether the data was identifiable or anonymous. Their willingness to sharing data for research purposes depended on the type of information being shared, what type of research would be undertaken and who would be doing the research. Participants were most concerned with genomics data sharing that could lead to discrimination (insurance and employment), data being used for marketing, data security, or commercial use. Conclusions Most participants were willing to share their genomic data from medical records with researchers, as long as permission for use was sought. However, the existing policies related to this process in Queensland do not reflect participant expectations for how this is achieved, particularly with anonymous genomics data. This inconsistency may be addressed by process changes, such as inclusion of research in addition to clinical consent or general research data consent programs.

Acute rheumatic fever and rheumatic heart disease (ARF/RHD) have long been described as autoimmune sequelae of Streptococcus pyogenes or group A streptococcal (GAS) infection. Both antibody and T-cell responses against immunodominant GAS virulence factors, including M protein, cross-react with host tissue proteins, triggering an inflammatory response leading to permanent heart damage. However, in some ARF/RHD-endemic regions, throat carriage of GAS is low. Because Streptococcus dysgalactiae subspecies equisimilis organisms, also known as β-hemolytic group C streptococci and group G streptococci (GGS), also express M protein, we postulated that streptococci other than GAS may have the potential to initiate or exacerbate ARF/RHD. Using a model initially developed to investigate the uniquely human disease of ARF/RHD, we have discovered that GGS causes interleukin 17A/interferon γ-induced myocarditis and valvulitis, hallmarks of ARF/RHD. Remarkably the histological, immunological, and functional changes in the hearts of rats exposed to GGS are identical to those exposed to GAS. Furthermore, antibody cross-reactivity to cardiac myosin was comparable in both GGS- and GAS-exposed animals, providing additional evidence that GGS can induce and/or exacerbate ARF/RHD.

The natural course of Chlamydia trachomatis urogenital tract infections varies between individuals. While protective immunity can occur, some women can become reinfected, contributing to the development of severe pathology. While the reasons for these differences are unknown, an individual's response to induced interferon-γ (IFN-γ) is suggested to be critical. IFN-γ induction of the enzyme indoleamine 2,3-dioxygenase, which depletes tryptophan, may be the key. One hypothesis suggests that indole-producing bacteria in the vaginal microbiota can provide a substrate for the Chlamydia to synthesize tryptophan, rescuing the Chlamydia from host IFN-γ attack. We studied a cohort of 25 women who were either, Chlamydia negative, Chlamydia positive with a single infection, or Chlamydia positive with repeated infection, to test our hypothesis. We characterized their vaginal microbiota, cytokine response, as well as their tryptophan, kynurenine and indole concentrations directly in vaginal secretions. We found that C. trachomatis urogenital tract infections either initial or repeat infections, were associated with elevated vaginal kynurenine/tryptophan ratios, primarily as a result of elevated kynurenine levels. In addition, vaginal microbiota of community state type (CST) IV showed significantly lower vaginal tryptophan levels compared to CST I and III, which might be related to a higher abundance of indole producers found within this group. Furthermore, we found a higher abundance of indole producers in women who cleared their Chlamydia infection post antibiotic treatment. This study demonstrates for the first time in vivo, the association between high vaginal kynurenine/tryptophan ratios and C. trachomatis infections. In addition, tryptophan depletion was associated with vaginal microbiota of CST IV. © 2018 Ziklo, Vidgen, Taing, Huston and Timms.

The intake of nuts has been linked to a reduced risk of cardiovascular disease (CVD) and diabetes in large cohort studies. One potential contributing mechanism may be the ability of nuts to improve post-meal glycemic response. We, therefore, examined the effect of nuts alone and in combination with white bread on postprandial glycemia.30, 60 and 90 g (approximately 1, 2 and 3 ounces) of mixed nuts were consumed with and without 50 g available carbohydrate from white bread by 10-14 normoglycemic and 5-10 type 2 diabetic subjects. Glycemic response (GR) was assessed by calculating the incremental area under the 2 h blood glucose curve. All three doses of mixed nuts, when fed alone, significantly reduced the glycemic response in both normoglycemic and diabetic patients. Furthermore, in the normoglycemic subjects, adding nuts to white bread progressively reduced the GR of the meal by 11.2 ± 11.6%, 29.7 ± 12.2% and 53.5 ± 8.5% for the 30, 60, and 90 g doses (P = 0.354, P = 0.031 and P 0.001, respectively), while in subjects with type 2 diabetes, the effect was half of that seen in the non-diabetic subjects (P = 0.474, P = 0.113 and P = 0.015, respectively).Nuts alone have little effect on post-meal blood glucose response. Furthermore, when taken with bread, nuts progressively reduce the glycemic response in a dose-dependent manner. While these findings support a short-term benefit for nuts in postprandial glucose response, more studies are required to determine whether these acute benefits result in long-term improvements in glycemic control.

Aims/hypothesis Sugar has been suggested to promote obesity, diabetes and coronary heart disease (CHD), yet fruit, despite containing sugars, may also have a low glycaemic index (GI) and all fruits are generally recommended for good health. We therefore assessed the effect of fruit with special emphasis on low GI fruit intake in type 2 diabetes. Methods This secondary analysis involved 152 type 2 diabetic participants treated with glucose-lowering agents who completed either 6 months of high fibre or low GI dietary advice, including fruit advice, in a parallel design. Results Change in low GI fruit intake ranged from −3.1 to 2.7 servings/day. The increase in low GI fruit intake significantly predicted reductions in HbA1c (r = −0.206, p = 0.011), systolic blood pressure (r = −0.183, p = 0.024) and CHD risk (r = −0.213, p = 0.008). Change in total fruit intake ranged from −3.7 to 3.2 servings/day and was not related to study outcomes. In a regression analysis including the eight major carbohydrate foods or classes of foods emphasised in the low GI diet, only low GI fruit and bread contributed independently and significantly to predicting change in HbA1c. Furthermore, comparing the highest with the lowest quartile of low GI fruit intake, the percentage change in HbA1c was reduced by −0.5% HbA1c units (95% CI 0.2–0.8 HbA1c units, p

Dietary non-oil-seed pulses (chickpeas, beans, peas, lentils, etc.) are a good source of slowly digestible carbohydrate, fibre and vegetable protein and a valuable means of lowering the glycaemic-index (GI) of the diet. To assess the evidence that dietary pulses may benefit glycaemic control, we conducted a systematic review and meta-analysis of randomised controlled experimental trials investigating the effect of pulses, alone or as part of low-GI or high-fibre diets, on markers of glycaemic control in people with and without diabetes.We searched MEDLINE, EMBASE, CINAHL, and the Cochrane Library for relevant controlled trials ofor=7 days. Two independent reviewers (A. Esfahani and J. M. W. Wong) extracted information on study design, participants, treatments and outcomes. Data were pooled using the generic inverse variance method and expressed as standardised mean differences (SMD) with 95% CIs. Heterogeneity was assessed by chi (2) and quantified by I (2). Meta-regression models identified independent predictors of effects.A total of 41 trials (39 reports) were included. Pulses alone (11 trials) lowered fasting blood glucose (FBG) (-0.82, 95% CI -1.36 to -0.27) and insulin (-0.49, 95% CI -0.93 to -0.04). Pulses in low-GI diets (19 trials) lowered glycosylated blood proteins (GP), measured as HbA(1c) or fructosamine (-0.28, 95% CI -0.42 to -0.14). Finally, pulses in high-fibre diets (11 trials) lowered FBG (-0.32, 95% CI -0.49 to -0.15) and GP (-0.27, 95% CI -0.45 to -0.09). Inter-study heterogeneity was high and unexplained for most outcomes, with benefits modified or predicted by diabetes status, pulse type, dose, physical form, duration of follow-up, study quality, macronutrient profile of background diets, feeding control and design.Pooled analyses demonstrated that pulses, alone or in low-GI or high-fibre diets, improve markers of longer term glycaemic control in humans, with the extent of the improvements subject to significant inter-study heterogeneity. There is a need for further large, well-designed trials.

To determine the effect on blood pressure of dietary advice to consume a combination of plant-based cholesterol-lowering foods (dietary portfolio).For 1 year, 66 hyperlipidemic subjects were prescribed diets high in plant sterols (1.0 g/1000 kcal), soy protein (22.5 g/1000 kcal), viscous fibers (10 g/1000 kcal) and almonds (22.5 g/1000 kcal). There was no control group. Seven-day diet record, blood pressure and body weight were monitored initially monthly and later at 2-monthly intervals throughout the study.Fifty subjects completed the 1-year study. When the last observation was carried forward for non-completers (n=9) or those who changed their blood pressure medications (n=7), a small mean reduction was seen in body weight 0.7+/-0.3 kg (P=0.036). The corresponding reductions from baseline in systolic and diastolic blood pressure at 1 year (n=66 subjects) were -4.2+/-1.3 mm Hg (P=0.002) and -2.3+/-0.7 mm Hg (P=0.001), respectively. Blood pressure reductions occurred within the first 2 weeks, with stable blood pressures 6 weeks before and 4 weeks after starting the diet. Diastolic blood pressure reduction was significantly related to weight change (r=0.30, n=50, P=0.036). Only compliance with almond intake advice related to blood pressure reduction (systolic: r=-0.34, n=50, P=0.017; diastolic: r=-0.29, n=50, P=0.041).A dietary portfolio of plant-based cholesterol-lowering foods reduced blood pressure significantly, related to almond intake. The dietary portfolio approach of combining a range of cholesterol-lowering plant foods may benefit cardiovascular disease risk both by reducing serum lipids and also blood pressure.

Objective Low-carbohydrate diets may be useful for weight loss. Diets high in vegetable proteins and oils may reduce the risk of coronary heart disease. The main objective was to determine the longer term effect of a diet that was both low-carbohydrate and plant-based on weight loss and low-density lipoprotein cholesterol (LDL-C). Design, setting, participants A parallel design study of 39 overweight hyperlipidaemic men and postmenopausal women conducted at a Canadian university-affiliated hospital nutrition research centre from April 2005 to November 2006. Intervention Participants were advised to consume either a low-carbohydrate vegan diet or a high-carbohydrate lacto-ovo vegetarian diet for 6 months after completing 1-month metabolic (all foods provided) versions of these diets. The prescribed macronutrient intakes for the low-carbohydrate and high-carbohydrate diets were: 26% and 58% of energy from carbohydrate, 31% and 16% from protein and 43% and 25% from fat, respectively. Primary outcome Change in body weight. Results 23 participants (50% test, 68% control) completed the 6-month ad libitum study. The approximate 4 kg weight loss on the metabolic study was increased to −6.9 kg on low-carbohydrate and −5.8 kg on high-carbohydrate 6-month ad libitum treatments (treatment difference (95% CI) −1.1 kg (−2.1 to 0.0), p=0.047). The relative LDL-C and triglyceride reductions were also greater on the low-carbohydrate treatment (treatment difference (95% CI) −0.49 mmol/L (−0.70 to −0.28), p

OBJECTIVE: To examine whether Konjac-mannan (KJM) fiber improves metabolic control as measured by glycemia, lipidemia, and blood pressure in high-risk type 2 diabetic patients. RESEARCH DESIGN AND METHODS: A total of 11 hyperlipidemic and hypertensive type 2 diabetic patients treated conventionally by a low-fat diet and drug therapy participated. After an 8-week baseline, all were randomly assigned to take either KJM fiber-enriched test biscuits (0.7 g/412 kJ [100 kcal] of glucomannan) or matched placebo wheat bran fiber biscuits during two 3-week treatment phases separated by a 2-week washout period. The diet in either case was metabolically controlled and conformed to National Cholesterol Education Program Step 2 guidelines, while medications were maintained constant. Efficacy measures included serum fructosamine, lipid profiles, apolipoproteins, blood pressure, body weight, and nutritional analysis. RESULTS: Compared with placebo, KJM significantly reduced the metabolic control primary end points: serum fructosamine (5.7%, P = 0.007, adjusted alpha = 0.0167), total:HDL cholesterol ratio (10%, P = 0.03, adjusted alpha = 0.05), and systolic blood pressure (sBP) (6.9%, P = 0.02, adjusted alpha = 0.025). Secondary end points, including body weight, total, LDL, and HDL cholesterol, triglycerides, apolipoproteins A-1, B, and their ratio, glucose, insulin, and diastolic blood pressure, were not significant after adjustment by the Bonferroni-Hochberg procedure. CONCLUSIONS: KJM fiber added to conventional treatment may ameliorate glycemic control, blood lipid profile, and sBP in high-risk diabetic individuals, possibly improving the effectiveness of conventional treatment in type 2 diabetes.

Background Low-carbohydrate, high–animal protein diets, which are advocated for weight loss, may not promote the desired reduction in low-density lipoprotein cholesterol (LDL-C) concentration. The effect of exchanging the animal proteins and fats for those of vegetable origin has not been tested. Our objective was to determine the effect on weight loss and LDL-C concentration of a low-carbohydrate diet high in vegetable proteins from gluten, soy, nuts, fruits, vegetables, cereals, and vegetable oils compared with a high-carbohydrate diet based on low-fat dairy and whole grain products. Methods A total of 47 overweight hyperlipidemic men and women consumed either (1) a low-carbohydrate (26% of total calories), high–vegetable protein (31% from gluten, soy, nuts, fruit, vegetables, and cereals), and vegetable oil (43%) plant-based diet or (2) a high-carbohydrate lacto-ovo vegetarian diet (58% carbohydrate, 16% protein, and 25% fat) for 4 weeks each in a parallel study design. The study food was provided at 60% of calorie requirements. Results Of the 47 subjects, 44 (94%) (test, n = 22 [92%]; control, n = 22 [96%]) completed the study. Weight loss was similar for both diets (approximately 4.0 kg). However, reductions in LDL-C concentration and total cholesterol–HDL-C and apolipoprotein B–apolipoprotein AI ratios were greater for the low-carbohydrate compared with the high-carbohydrate diet (−8.1% [ P = .002], −8.7% [ P = .004], and −9.6% [ P = .001], respectively). Reductions in systolic and diastolic blood pressure were also seen (−1.9% [ P = .052] and −2.4% [ P = .02], respectively). Conclusion A low-carbohydrate plant-based diet has lipid-lowering advantages over a high-carbohydrate, low-fat weight-loss diet in improving heart disease risk factors not seen with conventional low-fat diets with animal products. Trial Registration clinicaltrials.gov Identifier:NCT00256516

Objective: The insulin-like growth factor (IGF) system has been related to cell proliferation, obesity, diabetes, hyperinsulinemia and endometrial cancer risk. We used data from a case-control study conducted in Italy to provide additional information on the relation between the IGF system and endometrial cancer. Methods: A case-control study was conducted between 1999 and 2002 in Italy, including a total of 73 women with incident, histologically confirmed endometrial cancer and 108 controls admitted to the same hospital network for acute, nonneoplastic diseases. All subjects were interviewed using a validated questionnaire. Results: The odds ratios for endometrial cancer comparing the highest versus the lowest tertile of various IGF components were as follows: 0.5 [95% confidence interval (CI) 0.2–1.2] for free IGF-I, 1.1 (95% CI 0.5–2.6) for total IGF-I, 1.2 (95% CI 0.6–2.6) for total IGF-II, 2.4 (95% CI 1.0–5.9) for IGF binding protein (IGFBP)-1 and 0.8 (95% CI 0.4–2.0) for IGFBP-3. Further allowance for all IGF components in the model did not modify the results. The direct relation with IGFBP-1 was stronger and limited to heavier and older women. Conclusions: The present findings suggest a limited effect of the IGF system on endometrial cancer risk. Increasing IGFBP-1 levels seem to be associated with endometrial cancer risk in older women and in women with a higher body mass index.

Objective: To determine the effect of high-protein diets, which have recently been promoted for their health benefits, on urinary calcium losses and bone turnover in older subjects. Design: Randomized controlled cross-over study. Setting: Teaching hospital and university. Subjects: Twenty hyperlipidemic men and postmenopausal women (age 56±2 y) completed the study. Interventions: One-month test and control phases during which subjects consumed equi-energy metabolic diets high in calcium (1578 and 1593 mg/day, respectively). On the test diet 11% of total dietary energy from starch in the control bread was replaced by protein (wheat gluten), resulting in 27% of energy from protein on the test diet vs 16% on the control diet. Main outcome measure: Urinary calcium excretion. Results: Compared with the control diet, at week 4, the test diet increased mean (±s.e.m.) 24 h urinary output of calcium (139±15 vs 227±21 mg, P=0.004). The treatment difference in urinary calcium loss correlated with the serum anion gap as a marker of metabolic acid production (r=0.57, P=0.011). Serum calcium levels were marginally lower 2.41±0.02 vs 2.38±0.02 mmol/l (P=0.075), but there was no significant treatment difference in calcium balance, possibly related to the high background calcium intake on both diets. Conclusions: In the presence of high dietary calcium intakes the vegetable protein gluten does not appear to have a negative effect on calcium balance despite increased urinary calcium loss. Sponsorship: The University-Industry Research Partnership Program of the Natural Sciences and Engineering Research Council of Canada, Loblaw Brands Limited, Toronto, ON, and Kraft Canada Inc. Don Mills, ON. DJAJ is funded as a Canada Research Chair in Metabolism and Nutrition at the University of Toronto by the Federal Government of Canada, Ottawa.

OBJECTIVE: Dietary fiber has recently received recognition for reducing the risk of developing diabetes and heart disease. The implication is that it may have therapeutic benefit in prediabetic metabolic conditions. To test this hypothesis, we investigated the effect of supplementing a high-carbohydrate diet with fiber from Konjac-mannan (KJM) on metabolic control in subjects with the insulin resistance syndrome. RESEARCH DESIGN AND METHODS: We screened 278 free-living subjects between the ages of 45 and 65 years from the Canadian-Maltese Diabetes Study. A total of 11 (age 55+/-4 years, BMI 28+/-1.5 kg/m2) were recruited who satisfied the inclusion criteria: impaired glucose tolerance, reduced HDL cholesterol, elevated serum triglycerides, and moderate hypertension. After an 8-week baseline, they were randomly assigned to take either KJM fiber-enriched test biscuits (0.5 g of glucomannan per 100 kcal of dietary intake or 8-13 g/day) or wheat bran fiber (WB) control biscuits for two 3-week treatment periods separated by a 2-week washout. The diets were isoenergetic, metabolically controlled, and conformed to National Cholesterol Education Program Step 2 guidelines. Serum lipids, glycemic control, and blood pressure were the outcome measures. RESULTS: Decreases in serum cholesterol (total, 12.4+/-3.1%, P

193 (P>0.05) and -0.05±0.06 HbA1c (P>0.05). Significant differences were also seen between nuts and muffins with greater falls on nuts for LDL-C (-0.19±0.12 mmol/L, P=0.03). Nut intake directly related to change in LDL-C (r= -.24, n=98, P

aims: Because of the high risk for the development of type 2 diabetes after gestational diabetes, clinical practice guidelines recommend screening with an OGTT between 6 weeks and 6 months after delivery for women who had gestational diabetes during pregnancy. The aim of this study was to evaluate trends over time in post-partum screening for diabetes after gestational diabetes. Methods: The study used administrative data sources that provide detailed information on the health care utilisation of all residents of the Canadian province of Ontario (population=12 million). All women aged 17 to 49 without pre-existing diabetes who delivered between April 1994 and March 2008 were identified. Each woman who had gestational diabetes was matched with one who did not on age, region and year/quarter of delivery. For each year/quarter and for each group, the frequency of OGTTs and of any test that might be used to diagnose type 2 diabetes (i.e., OGTT, fasting glucose, random glucose or A1c) was determined up to 6 months post-partum. results: Screening with OGTTs after pregnancy with gestational diabetes increased from between 4 and 7% of pregnancies per year/quarter at the beginning of the study to between 13 and 17% of pregnancies at the end. This markedly exceeded the secular trend seen after pregnancies without gestational diabetes, where screening frequency increased from between 0 and 0.3% of pregnancies at the beginning to between 0.3 and 0.6% of pregnancies at the end. The use of any potential test that might diagnose type 2 diabetes after gestational diabetes increased from between 26 and 28% of pregnancies at the beginning of the study period to between 35 and 40% of pregnancies at the end. conclusion: Although an increasing number of women with pregnancies complicated by gestational diabetes were receiving OGTTs post-partum, the overwhelming majority of women were not receiving these tests. Even when considering a variety of tests that might have been used to diagnose type 2 diabetes, fewer than 40% of women with gestational diabetes were tested. This finding of inadequate screening in a high-risk population suggests that a large number of women of child-bearing age with type 2 diabetes remain undiagnosed.