A genetic variant in telomerase reverse transcriptase (TERT) modifies cancer risk in Lynch syndrome patients harbouring pathogenic MSH2 variants

Individuals with Lynch syndrome (LS), have an increased risk of developing cancer. Common genetic variants of telomerase reverse transcriptase (TERT) have been associated with a wide range of cancers, including colorectal cancer (CRC) in LS. We combined genotype data from 1881 LS patients, carrying pathogenic variants in MLH1, MSH2 or MSH6, for rs2075786 (G>A, intronic variant), 1207 LS patients for rs2736108 (C>T, upstream variant) and 1201 LS patients for rs7705526 (C>A, intronic variant). The risk of cancer was estimated by heterozygous/homozygous odds ratio (OR) with mixed-effects logistic regression to adjust for gene/gender/country of sample origin considering family identity. The AA genotype of SNP rs2075786 is associated with 85% higher odds at developing cancer compared to GG genotype in MSH2 pathogenic variant carriers (p = 0.0160). Kaplan-Meier analysis also shows an association for rs2075786; the AA allele for MSH2 variant carriers confers risk for earlier diagnosis of LS cancer (log-rank p = 0.0011). We report a polymorphism in TERT to be a possible modifier of disease risk in MSH2 pathogenic variant carriers. The rs2075786 SNP in TERT is associated with a differential risk of developing cancer for MSH2 pathogenic variant carriers. Use of this information has the potential to personalise screening protocols for LS patients

Global variation in diabetes diagnosis and prevalence based on fasting glucose and hemoglobin A1c

Fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c) are both used to diagnose diabetes, but these measurements can identify different people as having diabetes. We used data from 117 population-based studies and quantified, in different world regions, the prevalence of diagnosed diabetes, and whether those who were previously undiagnosed and detected as having diabetes in survey screening, had elevated FPG, HbA1c or both. We developed prediction equations for estimating the probability that a person without previously diagnosed diabetes, and at a specific level of FPG, had elevated HbA1c, and vice versa. The age-standardized proportion of diabetes that was previously undiagnosed and detected in survey screening ranged from 30% in the high-income western region to 66% in south Asia. Among those with screen-detected diabetes with either test, the age-standardized proportion who had elevated levels of both FPG and HbA1c was 29-39% across regions; the remainder had discordant elevation of FPG or HbA1c. In most low- and middle-income regions, isolated elevated HbA1c was more common than isolated elevated FPG. In these regions, the use of FPG alone may delay diabetes diagnosis and underestimate diabetes prevalence. Our prediction equations help allocate finite resources for measuring HbA1c to reduce the global shortfall in diabetes diagnosis and surveillance

Worldwide trends in underweight and obesity from 1990 to 2022: a pooled analysis of 3663 population-representative studies with 222 million children, adolescents, and adults

Background Underweight and obesity are associated with adverse health outcomes throughout the life course. We estimated the individual and combined prevalence of underweight or thinness and obesity, and their changes, from 1990 to 2022 for adults and school-aged children and adolescents in 200 countries and territories. Methods We used data from 3663 population-based studies with 222 million participants that measured height and weight in representative samples of the general population. We used a Bayesian hierarchical model to estimate trends in the prevalence of different BMI categories, separately for adults (age ≥20 years) and school-aged children and adolescents (age 5–19 years), from 1990 to 2022 for 200 countries and territories. For adults, we report the individual and combined prevalence of underweight (BMI <18·5 kg/m2) and obesity (BMI ≥30 kg/m2). For schoolaged children and adolescents, we report thinness (BMI <2 SD below the median of the WHO growth reference) and obesity (BMI >2 SD above the median). Findings From 1990 to 2022, the combined prevalence of underweight and obesity in adults decreased in 11 countries (6%) for women and 17 (9%) for men with a posterior probability of at least 0·80 that the observed changes were true decreases. The combined prevalence increased in 162 countries (81%) for women and 140 countries (70%) for men with a posterior probability of at least 0·80. In 2022, the combined prevalence of underweight and obesity was highest in island nations in the Caribbean and Polynesia and Micronesia, and countries in the Middle East and north Africa. Obesity prevalence was higher than underweight with posterior probability of at least 0·80 in 177 countries (89%) for women and 145 (73%) for men in 2022, whereas the converse was true in 16 countries (8%) for women, and 39 (20%) for men. From 1990 to 2022, the combined prevalence of thinness and obesity decreased among girls in five countries (3%) and among boys in 15 countries (8%) with a posterior probability of at least 0·80, and increased among girls in 140 countries (70%) and boys in 137 countries (69%) with a posterior probability of at least 0·80. The countries with highest combined prevalence of thinness and obesity in school-aged children and adolescents in 2022 were in Polynesia and Micronesia and the Caribbean for both sexes, and Chile and Qatar for boys. Combined prevalence was also high in some countries in south Asia, such as India and Pakistan, where thinness remained prevalent despite having declined. In 2022, obesity in school-aged children and adolescents was more prevalent than thinness with a posterior probability of at least 0·80 among girls in 133 countries (67%) and boys in 125 countries (63%), whereas the converse was true in 35 countries (18%) and 42 countries (21%), respectively. In almost all countries for both adults and school-aged children and adolescents, the increases in double burden were driven by increases in obesity, and decreases in double burden by declining underweight or thinness. Interpretation The combined burden of underweight and obesity has increased in most countries, driven by an increase in obesity, while underweight and thinness remain prevalent in south Asia and parts of Africa. A healthy nutrition transition that enhances access to nutritious foods is needed to address the remaining burden of underweight while curbing and reversing the increase in obesit

Global variations in diabetes mellitus based on fasting glucose and haemogloblin A1c

Fasting plasma glucose (FPG) and haemoglobin A1c (HbA1c) are both used to diagnose diabetes, but may identify different people as having diabetes. We used data from 117 population-based studies and quantified, in different world regions, the prevalence of diagnosed diabetes, and whether those who were previously undiagnosed and detected as having diabetes in survey screening had elevated FPG, HbA1c, or both. We developed prediction equations for estimating the probability that a person without previously diagnosed diabetes, and at a specific level of FPG, had elevated HbA1c, and vice versa. The age-standardised proportion of diabetes that was previously undiagnosed, and detected in survey screening, ranged from 30% in the high-income western region to 66% in south Asia. Among those with screen-detected diabetes with either test, the agestandardised proportion who had elevated levels of both FPG and HbA1c was 29-39% across regions; the remainder had discordant elevation of FPG or HbA1c. In most low- and middle-income regions, isolated elevated HbA1c more common than isolated elevated FPG. In these regions, the use of FPG alone may delay diabetes diagnosis and underestimate diabetes prevalence. Our prediction equations help allocate finite resources for measuring HbA1c to reduce the global gap in diabetes diagnosis and surveillance.peer-reviewe

Effects of Nutritional Interventions during Pregnancy on Infant and Child Cognitive Outcomes:A Systematic Review and Meta-Analysis

Background: Epidemiological studies have demonstrated that folate, iodine and iron intake during pregnancy impacts on foetal brain development and cognitive function. However, in human studies, the relationship with other dietary nutrients is less clear. Objective: This systematic review aims to critically appraise the current literature and meta-analyses results from nutritional interventions during pregnancy that aimed to optimise infant and child cognitive outcomes. Design: Ten electronic databases were searched for articles published up to August 2017. The search was limited to articles published in English. Randomised controlled trials (RCTs) testing the impact of any nutritional intervention (dietary counselling, education, nutrient supplementation, fortified foods and/or foods) during pregnancy on cognitive outcomes of children (<10 years old). Two independent reviewers assessed study eligibility and quality using the American Dietetic Association quality criteria checklist for primary research. Standardised mean differences were used for nine cognitive domains to measure effects for meta-analyses. Results: A total of 34 RCTs were included (21 studies included children aged less than 35 months, 10 studies included children aged 36–60 months and 3 studies included children aged 61–119 months). The types of nutritional interventions included nutrient supplements, whole foods, fortified foods and nutrition education. The following nine cognition outcomes: attention, behaviour, crystallised intelligence, fluid intelligence, global cognition, memory, motor skills, visual processing, and problem solving were not significantly impacted by nutritional interventions, although 65% of studies conducted post-hoc data analyses and were likely to be underpowered. Although, long chain polyunsaturated fatty acids (LCPUFA) supplementation was associated with a marginal increase in crystallised intelligence (Effect size (ES): 0.25; 95% confidence interval (95% CI): −0.04, 0.53), the effect was not statistically significant (p = 0.09), with significant study heterogeneity (p = 0.00). Conclusions: LCPUFA supplementation may be associated with an improvement in child crystallised intelligence, however further research is warranted. The remaining eight cognition domains were not significantly impacted by maternal nutritional interventions

What is a ‘timely’ diagnosis? Exploring the preferences of Australian health service consumers regarding when a diagnosis of dementia should be disclosed

Abstract Background Recently the dementia field has shifted focus away from the early diagnosis debate in favour of ‘timely’ diagnosis. ‘Timely’ diagnosis disclosure takes into consideration the preferences and unique circumstances of the individual. Determining when diagnosis disclosure is ‘timely’ may be particularly complex if there are differing views between the individual, their family, and their health care providers regarding disclosure. This study explores the preferences of consumers regarding when a diagnosis of dementia should be communicated. Methods A cross-sectional survey was conducted with English-speaking adults attending outpatient clinics at an Australian hospital. Participants were recruited by a research assistant in the clinic waiting room and invited to complete the survey on a web-connected iPad. The survey included questions examining socio-demographics and experience with dementia. Two scenarios were used to explore preferences for timing of diagnosis disclosure. Results Of 446 participants, 92% preferred a diagnosis of dementia to be disclosed as soon as possible. Preferences were not associated with socio-demographics or previous dementia experience. Most participants also preferred disclosure to occur as soon as possible if their spouse or partner was diagnosed with dementia (88%). There was strong correlation between preferences for self and preferences for spouse (0.91). Conclusions These findings provide guidance to health care providers about preferences for disclosure of a dementia diagnosis, and may help to overcome potential barriers to timely diagnosis. As the prevalence of dementia increases, consumers’ preference for diagnosis to occur as soon as possible has important implications for the health system

Perceived problems with involvement in decision making about breast cancer treatment and care: A cross-sectional study

Objective: To examine perceived problems with involvement in medical decision making among people with breast cancer from various phases of the cancer care trajectory. Methods: Breast cancer outpatients (n = 663) from 13 treatment centres completed a survey of perceived involvement in treatment and care decisions in the last month, psychological distress, demographic and clinical factors. A subsample (n = 98) from three centres completed a follow-up survey on preferred and perceived treatment decision making roles. Results: Overall, 112 (17 %) of 663 respondents from 13 oncology centres had experienced problems with involvement in decision making about their treatment and care in the last month, and of these, 36 (32 %) reported an unmet need for help with this problem. Elevated psychological distress was associated with 5.7 times the odds of reporting this problem and 6.6 times the odds of reporting this unmet need in the last month. Among the follow-up subsample (n = 98), 39% (n = 38) reported discordance between preferred and perceived role in a major treatment decision. Psychological distress was not associated with this outcome. Conclusion: Psychological distress was significantly associated with recently experiencing problems with involvement in treatment and care decisions, but not with misalignment of preferred and perceived roles in prior major treatment decisions. Practice implications: There is a need to maintain support for patient involvement in healthcare decisions across the cancer care continuum. (C) 2020 Elsevier B.V. All rights reserved

Medical oncology outpatients’ preferences and experiences with advanced care planning: a cross-sectional study

Abstract Background Medical oncology outpatients are a group for whom advance care planning (ACP) activities are particularly relevant. Patient views can help prioritise areas for improving end of life communication. The study aimed to determine in a sample of medical oncology outpatients: (1) the perceived importance of participating in ACP activities; (2) the proportion of patients who have ever participated in ACP activities; and (3) the proportion of patients who had not yet participated in ACP activities who were willing to do so in next month. Methods Adult medical oncology outpatients in two Australian cancer treatment centres were consecutively approached to complete a pen-and-paper survey. Items explored perceived importance, previous participation, and willingness to participate across key ACP activities including: discussing wishes with their family or doctor; recording wishes in a written document; appointing a substitute decision maker (SDM); and discussing life-expectancy. Results 185 participants completed the survey (51% consent rate). Most patients agreed it was important to: discuss end of life wishes with family (85%) and doctors (70%) and formally record wishes (73%). Few had discussed end of life wishes with a doctor (11%), recorded their wishes (15%); chosen a SDM (28%); discussed life expectancy (30%); or discussed end of life wishes with family (30%). Among those who had not participated in ACP, most were willing to discuss life expectancy (66%); discuss end of life wishes with family (57%) and a doctor (55%); and formally record wishes (56%) in the next month. Fewer wanted to appoint a SDM (40%). Conclusion Although medical oncology outpatients perceive ACP activities are important, rates of uptake are relatively low. The willingness of many patients to engage in ACP activities suggests a gap in current ACP practice. Efforts should focus on ensuring patients and families have clarity about the legal and other ramifications of ACP activities, and better education and training of health care providers in initiating conversations about end of life issues

Additional file 2: of What is a ‘timely’ diagnosis? Exploring the preferences of Australian health service consumers regarding when a diagnosis of dementia should be disclosed

Survey items. (DOCX 25 kb