Primary high-grade non-anaplastic thyroid carcinoma: a retrospective study of 364 cases.

AIMS: We aimed to study the clinicopathological and molecular features of high-grade non-anaplastic thyroid carcinomas (HGTCs), a carcinoma with a prognosis intermediate between those of well-differentiated carcinoma and anaplastic carcinoma. METHODS AND RESULTS: This study included 364 HGTC patients: 200 patients (54.9%) were diagnosed with poorly differentiated thyroid carcinoma (PDTC), based on the Turin consensus (HGTC-PDTC), and 164 were diagnosed with high-grade features that did not meet the Turin criteria (HGTC-nonPDTC). HGTCs are aggressive: the 3-year, 5-year, 10-year and 20-year disease-specific survival (DSS) rates were 89%, 76%, 60%, and 35%, respectively. Although DSS was similar between HGTC-PDTC and HGTC-nonPDTC patients, HGTC-PDTC was associated with higher rate of radioactive iodine avidity, a higher frequency of RAS mutations, a lower frequency of BRAF V600E mutations and a higher propensity for distant metastasis (DM) than HGTC-nonPDTC. Independent clinicopathological markers of worse outcome were: older age, male sex, extensive necrosis and lack of encapsulation for DSS; older age, male sex and vascular invasion for DM-free survival; and older age, necrosis, positive margins and lymph node metastasis for locoregional recurrence-free survival. The frequencies of BRAF, RAS, TERT, TP53 and PTEN alterations were 28%, 40%, 55%, 11%, and 10%, respectively. TP53, PTEN and TERT were independent molecular markers associated with an unfavourable outcome, independently of clinicopathological parameters. The coexistence of BRAF V600E and TERT promoter mutation increased the risk of DM. CONCLUSIONS: The above data support the classification of HGTC as a single group with two distinct subtypes based on tumour differentiation: HGTC-PDTC and HGTC-nonPDTC.

Measuring coverage in MNCH: evaluation of community-based treatment of childhood illnesses through household surveys.

Community case management (CCM) is a strategy for training and supporting workers at the community level to provide treatment for the three major childhood diseases--diarrhea, fever (indicative of malaria), and pneumonia--as a complement to facility-based care. Many low- and middle-income countries are now implementing CCM and need to evaluate whether adoption of the strategy is associated with increases in treatment coverage. In this review, we assess the extent to which large-scale, national household surveys can serve as sources of baseline data for evaluating trends in community-based treatment coverage for childhood illnesses. Our examination of the questionnaires used in Demographic and Health Surveys (DHS) and Multiple Indicator Cluster Surveys (MICS) conducted between 2005 and 2010 in five sub-Saharan African countries shows that questions on care seeking that included a locally adapted option for a community-based provider were present in all the DHS surveys and in some MICS surveys. Most of the surveys also assessed whether appropriate treatments were available, but only one survey collected information on the place of treatment for all three illnesses. This absence of baseline data on treatment source in household surveys will limit efforts to evaluate the effects of the introduction of CCM strategies in the study countries. We recommend alternative analysis plans for assessing CCM programs using household survey data that depend on baseline data availability and on the timing of CCM policy implementation.

Predictors of traffic events due to hypoglycemia in adults with type 1 diabetes: A Brazilian prospective cohort study.

BACKGROUND: Individuals with type 1 diabetes (T1D) are exposed to an elevated risk of automobile accidents especially because of hypoglycemia that impairs physiological and defense responses. OBJECTIVES: To assess local risk factors for traffic events in T1D adult Brazilian patients. METHODS: This is a prospective study and 12-month follow-up to assess predictors for traffic events on a cohort of drivers with T1D (n = 168) in Brazil. The inclusion criteria for participants were Brazilian nationality, age ≥ 18 years-old, diagnosis of T1D for more than one year, driving license B, C or D categories (four-wheel vehicles), driving three-times per week or more, and checking blood glucose twice-daily or more. The primary outcome was hypoglycemia driving mishaps assessed by a seven-query questionnaire about the past 30 days. Secondary outcomes included driving mishaps not related to hypoglycemia. Statistical analysis was performed through Poisson regression models with robust variance estimarion, in which the measure of association is the relative risk. RESULTS: A total of 109 participants completed the 12-month follow-up. Most of them were men (66%) and 37 ± 11 years-old, and had a mean HbA1c of 8.2% (66 mmol/mol). In the follow up, the incidence of traffic events was high (70.6%); however, only a minority was attributed to hypoglycemia as the cause of the reported event (19.3%). The best predictors for new traffic events due to hypoglycemia were those related to driving characteristics. The best of them was a history of episodes of hypoglycemia while driving [RR 3.40 (1.22-9.43); p < 0.05]. CONCLUSIONS: We found that previous episodes of hypoglycemia while driving significantly increase the risk of new traffic events and are the best predictor for it. This highlights the need to assess the risks of traffic accidents especially in people who have had experienced episodes of hypoglycemia while driving.

When should fixed ratio basal insulin/glucagon-like peptide-1 receptor agonists combination products be considered?

Diabetes management with achievement and maintenance of good glycemic control is very challenging in patients requiring multiple daily injections. This article is focusing on broader use of recently approved fixed ratio combination therapies, basal insulin and glucagon-like peptide-1 receptor agonists (GLP1 RA). These combination therapy improve patient compliance and adherence with the therapy, decrease burden of multiple injection, target multiple abnormalities in the pathophysiology of diabetes, decrease postprandial hypoglycemia, assist in weight loss and decrease weight related comorbidities. These combinations were recently approved for use as first injectables after failure of oral agents. Review of combination treatment with existing fixed doses of basal insulin with GLP1 RA opens door for further clinical trials for other dose combinations that can be used, particularly for patients who need higher doses of insulin.