Understanding Pathways to the Diagnosis of Thyroid Cancer: Are There Ways We Can Reduce Over-Diagnosis?

BACKGROUND: The incidence of thyroid cancer has rapidly increased, and ecological evidence suggests this is due in some part to over-diagnosis. Understanding pathways to diagnosis could help determine whether unnecessary diagnosis can be avoided. METHODS: A population-based sample (n = 1007) of thyroid cancer patients diagnosed between July 2013 and August 2016 was recruited from Queensland, Australia (response rate 67%). Information from structured telephone interviews was used to describe diagnostic pathways for thyroid cancer, to investigate factors associated with diagnostic pathways, and to assess the most prevalent modes of diagnoses by which the lowest-risk, potentially over-diagnosed thyroid cancers (intrathyroidal microcarcinomas) are detected. RESULTS: Only 38% of participants presented with symptoms potentially related to thyroid cancer. Older age at diagnosis was associated with a lower prevalence of symptomatic diagnosis (prevalence ratio [PR] = 0.46 [confidence interval (CI) 0.31-0.68] for 70-79 vs. <30 years), as was frequent medical contact, while living in rural/regional areas was associated with a higher prevalence of symptomatic diagnosis (PR = 1.17 [CI 1.00-1.37] for rural/regional areas vs. major cities). Symptomatic diagnosis also occurred more for those whose tumors had adverse histopathological features (larger size, lymph node involvement, lymphovascular invasion). The likelihood of diagnosis of intrathyroidal microcarcinomas was greatest for those having surgical resection or monitoring for benign thyroid disease (PR = 3.87 [CI 2.81-5.32] and PR = 2.21 [CI 1.53-3.18], respectively). CONCLUSIONS: A minority of newly detected thyroid cancer cases were diagnosed because of symptoms. Access to medical care and factors related to cancer aggressiveness were associated with how diagnoses occurred. The likelihood of diagnosing the lowest-risk thyroid cancers was higher in situations related to management of other thyroid conditions. Adherence to thyroid management guidelines could reduce some thyroid cancer over-diagnosis, but ultimately better diagnostic tools are needed to differentiate between indolent cancers and those of clinical significance.

Social Demography of Transitional Dietary Patterns in Thailand: Prospective Evidence from the Thai Cohort Study.

In recent decades, a health-risk transition with changes in diet and lifestyle in low and middle-income countries (LMICs) led to an emergence of chronic diseases. These trends in Southeast Asian LMICs are not well studied. Here, we report on transitional dietary patterns and their socio-demographic predictors in Thai adults. Dietary data in 2015 were from a random sub-sample (N = 1075) of 42,785 Thai Cohort Study (TCS) members who completed all three TCS surveys (2005, 2009, 2013). Principle Component Analysis identified dietary patterns and multivariable linear regression assessed associations (Beta estimates (ß) and confidence intervals (CIs)) between socio-demographic factors and dietary intake pattern scores. Four dietary patterns emerged: Healthy Transitional, Fatty Western, Highly Processed, and Traditional. In women, higher income (≥30,001 Baht/month vs. ≤10,000) and managerial work (vs. office assistant) was associated with lower scores for Traditional (ß = -0.67, 95% CI -1.15, -0.19) and Fatty Western diets (ß = -0.60, 95% CI -1.14, -0.05), respectively. University education associated with lower Highly Processed (ß = -0.57, 95% CI -0.98, -0.17) and higher Traditional diet scores (ß = 0.42, 95% CI 0.03, 0.81). In men and women, urban residence associated with higher Fatty Western and lower Traditional diets. Local policy makers should promote healthy diets, particularly in urban residents, in men, and in low-SEP adults.

Incidence and risk factors for type 2 diabetes mellitus in transitional Thailand: results from the Thai cohort study.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is increasingly prevalent in countries undergoing rapid development, including Thailand. We assessed T2DM incidence over an 8-year period in a nationwide cohort of Thai adults. METHODS: Thai Cohort Study participants were surveyed in 2005, 2009 and 2013. The analysed cohort members were aged (15-88), did not have diabetes in 2005 and were followed up by questionnaire in 2013 (n=39 507). T2DM was ascertained using self-report, which has been validated using physician interviews. We calculated the 8-year cumulative incidence of T2DM. Multivariable logistic regression assessed associations between potential risk factors and T2DM incidence. RESULTS: 8-year cumulative incidence of T2DM (2005 to 2013) was 177 per 10 000 (95% CI 164 to 190). Crude and age-standardised cumulative incidences of T2DM by sex were 249 per 10 000 (95% CI 226 to 272) and 222 per 10 000 (95% CI 219 to 225) for men; and 119 per 10 000 (95% CI 105 to 133) and 96 per 10 000 (95% CI 94 to 98) for women, respectively. T2DM increased significantly for both sexes with increasing age and body mass index (BMI) (p trend <0.001 for both). Residence in an urban area as a child associated with T2DM among men and women (OR=1.4, 95% CI 1.1 to 1.7 and OR=1.4, 95% CI 1.01 to 1.79); this was no longer statistically significant after adjusting for BMI. Among men, smoking (OR=1.7, 95% CI 1.3 to 2.2) and alcohol intake (OR=1.8, 95% CI 1.1 to 3.0) were associated with T2DM. CONCLUSIONS: This study found that the sociodemographic and lifestyle changes that have accompanied Thailand's economic development are associated with T2DM risk in a large cohort of Thai adults. Our findings highlight the need to address these transitions to prevent a further increase in the national incidence of T2DM, particularly among Thai men.

Australia is continuing to make progress against cancer, but the regional and remote disadvantage remains.

OBJECTIVE: To measure progress, over the past decade, in reducing the disadvantage in cancer death rates among people living in regional and remote areas of Australia. DESIGN: Analysis of routinely collected death certificate and corresponding population data from the Australian Bureau of Statistics. SETTING: Population-based, Australia-wide comparison of mortality rates in regional and remote areas compared with metropolitan areas from 1 January 2001 to 31 December 2010. MAIN OUTCOME MEASURES: Absolute and relative excess of cancer deaths in regional and remote areas. RESULTS: The number of excess cancer deaths in regional and remote areas from 2001 to 2010 was 8878 (95% CI, 8187-9572). For men, the age-standardised mortality ratios (comparing regional and remote areas with metropolitan areas) showed no evidence of improvement, from 1.08 in 1997-2000 to 1.11 in 2006-2010. For women, they increased from 1.01 in 1997-2000 to 1.07 in 2006-2010. The age-standardised cancer death rate in regional and remote areas (annual percentage change [APC], - 0.6%; 95% CI, - 0.8% to - 0.4%) is decreasing more slowly than in metropolitan areas (APC, - 1.1%; 95% CI, - 1.3% to - 1.0%). CONCLUSIONS: The regional and remote disadvantage for cancer deaths has been recognised as a problem for more than two decades, yet we have made little progress. This is not surprising - we have not invested in research into solutions. The benefits of laboratory and clinical research to identify innovative cancer treatments will not be fully realised across the entire Australian population unless we also invest in health systems and policy research.

Avoiding risk at what cost? Putting use of medicines for breastfeeding women into perspective.

Breastfeeding women often need to take medicines, and therefore health professionals need to consider the effects of medication on lactation and the breastfed infant, and any associated risks. This commentary discusses the tragic case of a young woman with a history of mental illness who committed suicide in the postpartum period. She was determined to be a 'good mother' and breastfeed, and to avoid any potential adverse effects of medication on her breastfed infant. The final outcome was fatal for both mother and child. We argue that if women require medication during lactation, all risks need to be considered - the risk of not treating the maternal medical condition may greatly outweigh the potential risk to the breastfed infant.

Secular changes and predictors of adult height for 86 105 male and female members of the Thai Cohort Study born between 1940 and 1990.

BACKGROUND: Height trends can be useful indicators of population health but, despite Thailand's rapid socioeconomic development since the 1950s, few studies have examined accompanying secular changes in adult height or the effects of the transition on the heights of rural versus urban populations. This study therefore sought to document average heights in different age groups of rural and urban Thais and to investigate factors associated with attained height. METHODS: Data from 86,105 Thai Cohort Study participants was used to estimate mean heights for men and women in different birth year groups. Simple regression was used to calculate the change in height per decade of birth year among those based in rural or urban locations as children. Multiple linear regression was used to investigate effects of other childhood factors on height. RESULTS: Overall, average heights were found to have increased by approximately 1 cm per decade in those born between 1940 and 1990. However, the rate of increase was 0.4-0.5 cm per decade greater among urban-based Thais compared with those from the countryside. Parental education levels, household assets, birth size, sibling number, birth rank and region of residence were also significantly associated with adult height. CONCLUSIONS: These data suggest a marked secular increase in Thai heights in the second half of the 20th century probably reflecting improved childhood health and nutrition over this time. Rural-born Thais, who benefited to a lesser extent from the changes, may face future health challenges with greater risks of, among other things, obesity and its health consequences.

Pathways to the diagnosis of epithelial ovarian cancer in Australia.

OBJECTIVE: To describe the diagnostic pathways experienced by a large, representative group of Australian women with ovarian cancer, and to document the time between first presentation to a medical professional and clinical diagnosis. DESIGN, SETTING AND PARTICIPANTS: 1463 women with epithelial ovarian cancer from an Australia-wide population-based study (2002-2005) completed a telephone interview in which they described the events that led to the diagnosis of their cancer. MAIN OUTCOME MEASURES: Number and type of doctors consulted, investigations performed, referral patterns and the time from first presentation to diagnosis. RESULTS: Of the 1463 women, 145 had their cancer diagnosed incidentally and were excluded from analysis. Most of the remaining 1318 women (1222, 93%) presented first to their general practitioner. As a result of their first medical consultation, 75 women (6%) were given a diagnosis, and 484 (37%) were referred to a gynaecologist, gynaecological oncologist or oncologist for further assessment. Overall, 85% of women visited three or fewer doctors before their cancer was diagnosed; 66% of cancers were diagnosed within 1 month of the initial presentation, and 80% were diagnosed within 3 months. For 12% of women, the diagnostic process took longer than 6 months; this was more likely for women residing in remote Australia, those with lower incomes, and those presenting with abdominal pain or bowel symptoms, or with more than one symptom. CONCLUSIONS: Despite anecdotal suggestions to the contrary, most women with ovarian cancer in Australia are investigated and diagnosed promptly. The diagnostic process is more protracted for a minority of women, and the factors we found to be associated with diagnostic delay warrant further investigation.

Frequency of treatment-effect modification affecting indirect comparisons: a systematic review.

A key assumption of indirect comparisons is similarity, which means that, in the face of differences in patient characteristics or study methods, there is no treatment-effect modification across sides of the indirect comparison. We therefore conducted a systematic review of MEDLINE and EMBASE from inception to November 2009 to summarize currently available information about how frequently, on average, treatment-effect modification occurs across trials that might be used on different sides of an indirect comparison. Although similarity is a key assumption, there is currently no published evidence specifically for indirect comparisons about how frequently treatment-effect modification occurs. Six analyses were identified that assessed treatment-effect modification across studies included in direct head-to-head meta-analyses. Such analyses are relevant to indirect comparisons because the phenomenon being investigated would occur with similar frequency. They provide important information because lack of treatment-effect modification across sides of an indirect comparison cannot be directly assessed statistically; this is in contrast to direct head-to-head meta-analyses where Cochrane's Q statistic or I2 can be used. For ratio measures such as the odds ratio and relative risk, treatment-effect modification occurred for 10-33% of meta-analyses. For the risk difference (an arithmetic measure), the range was 15-46%. It is not prudent to assume similarity in an indirect comparison, based only on the result that ratio measures such as the odds ratio are reasonably robust to treatment-effect modification. All indirect comparisons should include a thorough narrative comparison of differences in patient characteristics and study methods. This will provide end users with the best evidence with which to make an assessment of the likelihood of treatment-effect modification and the plausibility of the similarity assumption.

Solid organ transplantation at the National Institutes of Health: development of a research-based transplantation practice.

The National Institutes of Health has established a clinical transplant research program focusing on translational research in kidney transplantation. The program has been developed with a multidisciplinary approach under a common administrative structure that integrates transplant physicians and surgeons with clinical laboratory and data analysis support personnel. The program has achieved excellent clinical outcomes despite focusing exclusively on investigational methods and serving a diverse and medically complex patient population. Novel approaches toward consenting, computer integration, and tissue acquisition have been layered over interventional and observational studies to serve the scientific mission while delivering quality transplant care.