The use of levothyroxine to treat subclinical hypothyroidism is controversial. We aimed to determine whether levothyroxine provided clinical benefits in older persons with this condition. We conducted a double-blind, randomized, placebo-controlled, parallel-group trial involving 737 adults who were at least 65 years of age and who had persisting subclinical hypothyroidism (thyrotropin level, 4.60 to 19.99 mIU per liter; free thyroxine level within the reference range). A total of 368 patients were assigned to receive levothyroxine (at a starting dose of 50 μg daily, or 25 μg if the body weight was <50 kg or the patient had coronary heart disease), with dose adjustment according to the thyrotropin level; 369 patients were assigned to receive placebo with mock dose adjustment. The two primary outcomes were the change in the Hypothyroid Symptoms score and Tiredness score on a thyroid-related quality-of-life questionnaire at 1 year (range of each scale is 0 to 100, with higher scores indicating more symptoms or tiredness, respectively; minimum clinically important difference, 9 points). The mean age of the patients was 74.4 years, and 396 patients (53.7%) were women. The mean (±SD) thyrotropin level was 6.40±2.01 mIU per liter at baseline; at 1 year, this level had decreased to 5.48 mIU per liter in the placebo group, as compared with 3.63 mIU per liter in the levothyroxine group (P<0.001), at a median dose of 50 μg. We found no differences in the mean change at 1 year in the Hypothyroid Symptoms score (0.2±15.3 in the placebo group and 0.2±14.4 in the levothyroxine group; between-group difference, 0.0; 95% confidence interval [CI], −2.0 to 2.1) or the Tiredness score (3.2±17.7 and 3.8±18.4, respectively; between-group difference, 0.4; 95% CI, −2.1 to 2.9). No beneficial effects of levothyroxine were seen on secondary-outcome measures. There was no significant excess of serious adverse events prespecified as being of special interest. Levothyroxine provided no apparent benefits in older persons with subclinical hypothyroidism. (Funded by European Union FP7 and others; TRUST ClinicalTrials.gov number, NCT01660126.)

Background: Better identification of complex patients could help to improve their care. However, the definition of patient complexity itself is far from obvious. We conducted a narrative review to identify, describe, and synthesize the definitions of patient complexity used in the last 25 years. Methods: We searched PubMed for articles published in English between January 1995 and September 2020, defining patient complexity. We extended the search to the references of the included articles. We assessed the domains presented in the definitions, and classified the definitions as based on (1) medical aspects (e.g., number of conditions) or (2) medical and/or non-medical aspects (e.g., socio-economic status). We assessed whether the definition was based on a tool (e.g., index) or conceptual model. Results: Among 83 articles, there was marked heterogeneity in the patient complexity definitions. Domains contributing to complexity included health, demographics, behavior, socio-economic factors, healthcare system, medical decision-making, and environment. Patient complexity was defined according to medical aspects in 30 (36.1%) articles, and to medical and/or non-medical aspects in 53 (63.9%) articles. A tool was used in 36 (43.4%) articles, and a conceptual model in seven (8.4%) articles. Conclusion: A consensus concerning the definition of patient complexity was lacking. Most definitions incorporated non-medical factors in the definition, underlining the importance of accounting not only for medical but also for non-medical aspects, as well as for their interrelationship.

Matrix Gla protein (MGP) is an important inhibitor of calcification. The objective of the present study of patients with type 2 diabetes and normal or slightly altered kidney function was to evaluate levels of inactive, dephospho-uncarboxylated MGP(dp-ucMGP) and total uncarboxylated MGP(t-ucMGP) and assess their links with biological and clinical parameters (including peripheral vascular calcification).