Use of levothyroxine for euthyroid, thyroid antibody positive women with infertility: Analyses of aggregate data from a survey of European thyroid specialists (Treatment of Hypothyroidism in Europe by Specialists: An International Survey).

OBJECTIVES: The use of levothyroxine (LT4) treatment aiming to improve fertility in euthyroid women with positive thyroid peroxidase antibodies (TPOAb) is not supported by the available evidence. The aim of the study was to document the use of LT4 by European thyroid specialists in such patients. DESIGN: The data presented derive from Treatment of Hypothyroidism in Europe by Specialists, an International Survey (THESIS), a questionnaire conducted between 2019 and 2021 to document the management of hypothyroidism by European thyroid specialists. Here, we report the aggregate results on the use of LT4 in infertile, euthyroid women with positive TPOAb. RESULTS: A total of 2316/5406 (42.8%) respondents stated that LT4 may be indicated in TPOAb positive euthyroid women with infertility. The proportion of those replying positively to this question varied widely across different countries (median 39.4, range 22.9%-83.7%). In multivariate analyses males (OR: 0.8; CI: 0.7-0.9) and respondents >60 years (OR: 0.7; 0.6-0.8) were the least inclined to consider LT4 for this indication. Conversely, respondents managing many thyroid patients ("weekly" [OR: 1.4; CI: 1.0-1.9], "daily" [OR: 1.8; CI: 1.3-2.4]) and practicing in Eastern Europe (OR: 1.5; CI: 1.3-1.9) were most likely to consider LT4. CONCLUSIONS: A remarkably high number of respondents surveyed between 2019 and 2021, would consider LT4 treatment in TPOAb positive euthyroid women with infertility. This view varied widely across countries and correlated with sex, age and workload, potentially influencing patient management. These results raise concerns about potential risks of overtreatment.

Acute effects of different types of cannabis on young adult and adolescent resting-state brain networks.

Adolescence is a time of rapid neurodevelopment and the endocannabinoid system is particularly prone to change during this time. Cannabis is a commonly used drug with a particularly high prevalence of use among adolescents. The two predominant phytocannabinoids are Delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), which affect the endocannabinoid system. It is unknown whether this period of rapid development makes adolescents more or less vulnerable to the effects of cannabis on brain-network connectivity, and whether CBD may attenuate the effects of THC. Using fMRI, we explored the impact of vaporized cannabis (placebo, THC: 8 mg/75 kg, THC + CBD: 8 mg/75 kg THC & 24 mg/75 kg CBD) on resting-state networks in groups of semi-regular cannabis users (usage frequency between 0.5 and 3 days/week), consisting of 22 adolescents (16-17 years) and 24 young adults (26-29 years) matched for cannabis use frequency. Cannabis caused reductions in within-network connectivity in the default mode (F[2,88] = 3.97, P = 0.022, η² = 0.018), executive control (F[2,88] = 18.62, P < 0.001, η² = 0.123), salience (F[2,88] = 12.12, P < 0.001, η² = 0.076), hippocampal (F[2,88] = 14.65, P < 0.001, η² = 0.087), and limbic striatal (F[2,88] = 16.19, P < 0.001, η² = 0.102) networks compared to placebo. Whole-brain analysis showed cannabis significantly disrupted functional connectivity with cortical regions and the executive control, salience, hippocampal, and limbic striatal networks compared to placebo. CBD did not counteract THC's effects and further reduced connectivity both within networks and the whole brain. While age-related differences were observed, there were no interactions between age group and cannabis treatment in any brain network. Overall, these results challenge the assumption that CBD can make cannabis safer, as CBD did not attenuate THC effects (and in some cases potentiated them); furthermore, they show that cannabis causes similar disruption to resting-state connectivity in the adolescent and adult brain.

Patients' Persistent Symptoms, Clinician Demographics, and Geo-Economic Factors Are Associated with Choice of Therapy for Hypothyroidism by European Thyroid Specialists: The "THESIS" Collaboration.

Background: Hypothyroidism is common, however, aspects of its treatment remain controversial. Our survey aimed at documenting treatment choices of European thyroid specialists and exploring how patients' persistent symptoms, clinician demographics, and geo-economic factors relate to treatment choices. Methods: Seventeen thousand two hundred forty-seven thyroid specialists from 28 countries were invited to participate in an online questionnaire survey. The survey included respondent demographic data and treatment choices for hypothyroid patients with persistent symptoms. Geo-economic data for each country were included in the analyses. Results: The response rate was 32.9% (6058 respondents out of 17,247 invitees). Levothyroxine (LT4) was the initial treatment preferred by the majority (98.3%). Persistent symptoms despite normal serum thyrotropin (TSH) while receiving LT4 treatment were reported to affect up to 10.0% of patients by 75.4% of respondents, while 28.4% reported an increasing such trend in the past 5 years. The principal explanations offered for patients' persistent symptoms were psychosocial factors (77.1%), comorbidities (69.2%), and unrealistic patient expectations (61.0%). Combination treatment with LT4+liothyronine (LT3) was chosen by 40.0% of respondents for patients who complained of persistent symptoms despite a normal TSH. This option was selected more frequently by female thyroid specialists, with high-volume practice, working in countries with high gross national income per capita. Conclusions: The perception of patients' dissatisfaction reported by physicians seems lower than that described by hypothyroid patients in previous surveys. LT4+LT3 treatment is used frequently by thyroid specialists in Europe for persistent hypothyroid-like symptoms even if they generally attribute such symptoms to nonendocrine causes and despite the evidence of nonsuperiority of the combined over the LT4 therapy. Pressure by dissatisfied patients on their physicians for LT3-containing treatments is a likely explanation. The association of the therapeutic choices with the clinician demographic characteristics and geo-economic factors in Europe is a novel information and requires further investigation.

Characteristics of specialists treating hypothyroid patients: the "THESIS" collaborative.

Introduction: Thyroid specialists influence how hypothyroid patients are treated, including patients managed in primary care. Given that physician characteristics influence patient care, this study aimed to explore thyroid specialist profiles and associations with geo-economic factors. Methods: Thyroid specialists from 28 countries were invited to respond to a questionnaire, Treatment of Hypothyroidism in Europe by Specialists: an International Survey (THESIS). Geographic regions were defined according to the United Nations Statistics Division. The national economic status was estimated using World Bank data on the gross national income per capita (GNI per capita). Results: 5,695 valid responses were received (response rate 33·0%). The mean age was 49 years, and 65·0% were female. The proportion of female respondents was lowest in Northern (45·6%) and highest in Eastern Europe (77·2%) (p <0·001). Respondent work volume, university affiliation and private practice differed significantly between countries (p<0·001). Age and GNI per capita were correlated inversely with the proportion of female respondents (p<0·01). GNI per capita was inversely related to the proportion of respondents working exclusively in private practice (p<0·011) and the proportion of respondents who treated >100 patients annually (p<0·01). Discussion: THESIS has demonstrated differences in characteristics of thyroid specialists at national and regional levels, strongly associated with GNI per capita. Hypothyroid patients in middle-income countries are more likely to encounter female thyroid specialists working in private practice, with a high workload, compared to high-income countries. Whether these differences influence the quality of care and patient satisfaction is unknown, but merits further study.

Associations between regular cannabis use and brain resting-state functional connectivity in adolescents and adults.

BACKGROUND/AIM: Cannabis use is highly prevalent in adolescents; however, little is known about its effects on adolescent brain function. METHOD: Resting-state functional magnetic resonance imaging was used in matched groups of regular cannabis users (N = 70, 35 adolescents: 16-17 years old, 35 adults: 26-29 years old) and non-regular-using controls (N = 70, 35 adolescents/35 adults). Pre-registered analyses examined the connectivity of seven major cortical and sub-cortical brain networks (default mode network, executive control network (ECN), salience network, hippocampal network and three striatal networks) using seed-based analysis methods with cross-sectional comparisons between user groups and age groups. RESULTS: The regular cannabis use group (across both age groups), relative to controls, showed localised increases in connectivity only in the ECN analysis. All networks showed localised connectivity differences based on age group, with the adolescents generally showing weaker connectivity than adults, consistent with the developmental effects. Mean connectivity across entire network regions of interest (ROIs) was also significantly decreased in the ECN in adolescents. However, there were no significant interactions found between age group and user group in any of the seed-based or ROI analyses. There were also no associations found between cannabis use frequency and any of the derived connectivity measures. CONCLUSION: Regular cannabis use is associated with changes in connectivity of the ECN, which may reflect allostatic or compensatory changes in response to regular cannabis intoxication. However, these associations were not significantly different in adolescents compared to adults.

The acute effects of cannabis with and without cannabidiol in adults and adolescents: A randomised, double-blind, placebo-controlled, crossover experiment.

BACKGROUND AND AIMS: Long-term harms of cannabis may be exacerbated in adolescence, but little is known about the acute effects of cannabis in adolescents. We aimed to (i) compare the acute effects of cannabis in adolescent and adult cannabis users and (ii) determine if cannabidiol (CBD) acutely modulates the effects of delta-9-tetrahydocannabinol (THC). DESIGN: Randomised, double-blind, placebo-controlled, crossover experiment. The experiment was registered on ClinicalTrials.gov (NCT04851392). SETTING: Laboratory in London, United Kingdom. PARTICIPANTS: Twenty-four adolescents (12 women, 16- to 17-year-olds) and 24 adults (12 women, 26- to 29-year-olds) who used cannabis 0.5-3 days/week and were matched on cannabis use frequency (mean = 1.5 days/week). INTERVENTION: We administered three weight-adjusted vaporised cannabis flower preparations: 'THC' (8 mg THC for 75 kg person); 'THC + CBD' (8 mg THC and 24 mg CBD for 75 kg person); and 'PLA' (matched placebo). MEASUREMENTS: Primary outcomes were (i) subjective 'feel drug effect'; (ii) verbal episodic memory (delayed prose recall); and (iii) psychotomimetic effect (Psychotomimetic States Inventory). FINDINGS: Compared with 'PLA', 'THC' and 'THC + CBD' significantly (P < 0.001) increased 'feel drug effect' (mean difference [MD] = 6.3, 95% CI = 5.3-7.2; MD = 6.8, 95% CI = 6.0-7.7), impaired verbal episodic memory (MD = -2.7, 95% CI = -4.1 to -1.4; MD = -2.9, 95% CI = -4.1 to -1.7) and increased psychotomimetic effects (MD = 7.8, 95% CI = 2.8-12.7; MD = 10.8, 95% CI = 6.2-15.4). There was no evidence that adolescents differed from adults in their responses to cannabis (interaction P ≥ 0.4). Bayesian analyses supported equivalent effects of cannabis in adolescents and adults (Bayes factor [BF01 ] >3). There was no evidence that CBD significantly modulated the acute effects of THC. CONCLUSIONS: Adolescent cannabis users are neither more resilient nor more vulnerable than adult cannabis users to the acute psychotomimetic, verbal memory-impairing or subjective effects of cannabis. Furthermore, in adolescents and adults, vaporised cannabidiol does not mitigate the acute harms caused by delta-9-tetrahydocannabinol.

The Effects of Acute Cannabis With and Without Cannabidiol on Neural Reward Anticipation in Adults and Adolescents.

BACKGROUND: Adolescents may respond differently to cannabis than adults, yet no previous functional magnetic resonance imaging study has examined acute cannabis effects in this age group. In this study, we investigated the neural correlates of reward anticipation after acute exposure to cannabis in adolescents and adults. METHODS: This was a double-blind, placebo-controlled, randomized, crossover experiment. Forty-seven adolescents (n = 24, 12 females, ages 16-17 years) and adults (n = 23, 11 females, ages 26-29 years) matched on cannabis use frequency (0.5-3 days/week) completed the Monetary Incentive Delay task during functional magnetic resonance imaging after inhaling cannabis with 0.107 mg/kg Δ9-tetrahydrocannabinol ("THC") (8 mg THC for a 75-kg person) or with THC plus 0.320 mg/kg cannabidiol ("THC+CBD") (24 mg CBD for a 75-kg person), or placebo cannabis. We investigated reward anticipation activity with whole-brain analyses and region of interest analyses in the right and left ventral striatum, right and left anterior cingulate cortex, and right insula. RESULTS: THC reduced anticipation activity compared with placebo in the right (p = .005, d= 0.49) and left (p = .003, d = 0.50) ventral striatum and the right insula (p = .01, d = 0.42). THC+CBD reduced activity compared with placebo in the right ventral striatum (p = .01, d = 0.41) and right insula (p = .002, d = 0.49). There were no differences between "THC" and "THC+CBD" conditions and no significant drug by age group interaction effect, supported by Bayesian analyses. There were no significant effects in the whole-brain analyses. CONCLUSIONS: In weekly cannabis users, cannabis suppresses the brain's anticipatory reward response to money, and CBD does not modulate this effect. Furthermore, the adolescent reward circuitry is not differentially sensitive to acute effects of cannabis on reward anticipation.

Anhedonia, Apathy, Pleasure, and Effort-Based Decision-Making in Adult and Adolescent Cannabis Users and Controls.

BACKGROUND: Cannabis use may be linked with anhedonia and apathy. However, previous studies have shown mixed results, and few have examined the association between cannabis use and specific reward sub-processes. Adolescents may be more vulnerable than adults to harmful effects of cannabis. This study investigated (1) the association between non-acute cannabis use and apathy, anhedonia, pleasure, and effort-based decision-making for reward; and (2) whether these relationships were moderated by age group. METHODS: We used data from the "CannTeen" study. Participants were 274 adult (26-29 years) and adolescent (16-17 years) cannabis users (1-7 d/wk use in the past 3 months) and gender- and age-matched controls. Anhedonia was measured with the Snaith-Hamilton Pleasure Scale (n = 274), and apathy was measured with the Apathy Evaluation Scale (n = 215). Effort-based decision-making for reward was measured with the Physical Effort task (n = 139), and subjective wanting and liking of rewards was measured with the novel Real Reward Pleasure task (n = 137). RESULTS: Controls had higher levels of anhedonia than cannabis users (F1,258 = 5.35, P = .02, η p2 = .02). There were no other significant effects of user-group and no significant user-group*age-group interactions. Null findings were supported by post hoc Bayesian analyses. CONCLUSION: Our results suggest that cannabis use at a frequency of 3 to 4 d/wk is not associated with apathy, effort-based decision-making for reward, reward wanting, or reward liking in adults or adolescents. Cannabis users had lower anhedonia than controls, albeit at a small effect size. These findings are not consistent with the hypothesis that non-acute cannabis use is associated with amotivation.

The CannTeen Study: Cannabis use disorder, depression, anxiety, and psychotic-like symptoms in adolescent and adult cannabis users and age-matched controls.

BACKGROUND: Adolescence is characterised by psychological and neural development. Cannabis harms may be accentuated during adolescence. We hypothesised that adolescents would be more vulnerable to the associations between cannabis use and mental health and addiction problems than adults. METHOD: As part of the 'CannTeen' study, we conducted a cross-sectional analysis. There were 274 participants: split into groups of adolescent users (n = 76; 16-17 years old) and controls (n = 63), and adult users (n = 71; 26-29 years old) and controls (n = 64). Among users, cannabis use frequency ranged from 1 to 7 days/week, while controls had 0-10 lifetime exposures to cannabis. Adolescent and adult cannabis users were matched on cannabis use frequency (mean=4 days/week). We measured Diagnostic and Statistical Manual (DSM-5) Cannabis Use Disorder (CUD), Beck Depression Inventory, Beck Anxiety Inventory and Psychotomimetic States Inventory-adapted. RESULTS: After adjustment for covariates, adolescent users were more likely to have severe CUD than adult users (odd ratio = 3.474, 95% confidence interval (CI) = 1.501-8.036). Users reported greater psychotic-like symptoms than controls (b = 6.004, 95% CI = 1.211-10.796) and adolescents reported greater psychotic-like symptoms than adults (b = 5.509, 95% CI = 1.070-9.947). User-group was not associated with depression or anxiety. No significant interactions between age-group and user-group were identified. Exploratory analyses suggested that cannabis users with severe CUD had greater depression and anxiety levels than cannabis users without severe CUD. CONCLUSION: Adolescent cannabis users are more likely than adult cannabis users to have severe CUD. Adolescent cannabis users have greater psychotic-like symptoms than adult cannabis users and adolescent controls, through an additive effect. There was no evidence of an amplified vulnerability to cannabis-related increases in subclinical depression, anxiety or psychotic-like symptoms in adolescence. However, poorer mental health was associated with the presence of severe CUD.

Neural responses to reward anticipation and feedback in adult and adolescent cannabis users and controls.

Chronic use of drugs may alter the brain's reward system, though the extant literature concerning long-term cannabis use and neural correlates of reward processing has shown mixed results. Adolescents may be more vulnerable to the adverse effects of cannabis than adults; however, this has not been investigated for reward processing. As part of the 'CannTeen' study, in the largest functional magnetic resonance imaging study of reward processing and cannabis use to date, we investigated reward anticipation and feedback in 125 adult (26-29 years) and adolescent (16-17 years) cannabis users (1-7 days/week cannabis use) and gender- and age-matched controls, using the Monetary Incentive Delay task. Blood-oxygen-level-dependent responses were examined using region of interest (ROI) analyses in the bilateral ventral striatum for reward anticipation and right ventral striatum and left ventromedial prefrontal cortex for feedback, and exploratory whole-brain analyses. Results showed no User-Group or User-Group × Age-Group effects during reward anticipation or feedback in pre-defined ROIs. These null findings were supported by post hoc Bayesian analyses. However, in the whole-brain analysis, cannabis users had greater feedback activity in the prefrontal and inferior parietal cortex compared to controls. In conclusion, cannabis users and controls had similar neural responses during reward anticipation and in hypothesised reward-related regions during reward feedback. The whole-brain analysis revealed tentative evidence of greater fronto-parietal activity in cannabis users during feedback. Adolescents showed no increased vulnerability compared with adults. Overall, reward anticipation and feedback processing appear spared in adolescent and adult cannabis users, but future longitudinal studies are needed to corroborate this.

Clinical Management of Women with Newly Diagnosed Osteoporosis: Data from Everyday Practice in Bulgaria.

INTRODUCTION: The real duration of osteoporosis treatment in clinical practice is still not well described. The primary objective is to estimate the proportion of patients who stayed on treatment during a 4-year follow-up, and the secondary objective is to estimate the proportion of patients who switched treatment and the reasons for switch or discontinuation. METHODS: This was a national retrospective chart review, based on routine clinical data. Data were collected electronically from medical records in 33 representative primary care physicians' sites. Inclusion criteria were women with postmenopausal osteoporosis that have received initial treatment prescription following diagnosis by DXA between January 1, 2012 and December 31, 2014, and at least a 12-month database history after the index date. Exclusion criteria were women receiving treatment for osteoporosis and follow-up at secondary care physicians' sites only. All statistical analyses were performed with the R statistical package. RESULTS: A total of 1206 female patients with newly diagnosed osteoporosis and treatment initiation were followed for 4 years. The majority (88.3%) had no history of previous fractures. Bone mineral density data were available in 70.1%. Endocrinology was the most common specialty among prescribing specialists (40.0%), followed by rheumatology (30.3%). Bisphosphonates (BPs) were the most common initial treatment (72.7%), followed by denosumab (20.1%). Ibandronate (70.2%) and alendronate (24.2%) constituted the majority of all prescribed BPs; 731 patients remained on treatment during the second year (60.6%), 524 during the third year (43.4%) and 403 (33.4%)-at study end (fourth year). In all groups, except that on denosumab, the most common reason for switching to another treatment was presumed lack of effect. The main reasons for treatment discontinuation were financial on the patient's part. CONCLUSIONS: The duration of osteoporosis treatment in real-world clinical practice is far from optimal: < 3-4 years irrespective of fracture risk. Factors other than medical considerations are at play, mainly limitations set by the Health Insurance Fund. The health authorities should be aware of this.

Acute effects of MDMA on trust, cooperative behaviour and empathy: A double-blind, placebo-controlled experiment.

BACKGROUND: 3,4-Methylenedioxymethamphetamine (MDMA) is being actively researched as an adjunct to psychotherapy. It may be beneficial to trust, empathy and cooperative behaviour due to its acute prosocial effects. AIM: To test (a) the acute effects of MDMA on measures of empathy, trust and cooperative behaviour, and (b) subacute changes in mood three days after MDMA administration. METHODS: Twenty-five participants (n=7 female), participated in this double-blind, repeated-measures, placebo-controlled experiment. Participants attended two acute sessions, one week apart. Each acute session was followed by a subacute session three days later. Participants received placebo (100 mg ascorbic acid) during one acute session, and MDMA (100 mg MDMA-HCl) at the other, with order counterbalanced. Participants completed the following tasks assessing prosocial behaviour: a trust investment task, a trustworthy face rating task, an empathic stories task, a public project game, a dictator game and an ultimatum game. Participants reported subjective effects. Blood was taken pre-drug, 2 and 4 hours post-drug, and tested for plasma MDMA levels. RESULTS: MDMA acutely increased self-reported 'closeness to others' and 'euphoria' and increased plasma concentrations of MDMA. MDMA did not significantly change task-based empathy, trust or cooperative behaviour. Using Bayesian analyses, we found evidence that MDMA and placebo did not differ in their effects on empathy and cooperative behaviour. MDMA did not significantly change subacute mood and this was supported by our Bayesian analyses. CONCLUSION: Despite augmentation in plasma MDMA levels and subjective drug effects, we found no increase in prosocial behaviour in a laboratory setting.

Ketamine as a mental health treatment: Are acute psychoactive effects associated with outcomes? A systematic review.

Esketamine was recently licensed by the US Food and Drug Administration (FDA) and European Drug Agency (EDA) for use in treatment resistant depression (TRD), and further research indicates ketamine as a possible treatment in other mental health conditions. While the underlying mechanisms remain unclear, it has been hypothesised that ketamine's acute psychoactive effects may be associated with psychiatric treatment efficacy. We systematically reviewed the evidence for this association. The databases Medline, Embase and PsychInfo were searched up to June 2019. Studies were included if they enrolled adults with a psychiatric diagnosis, assessed acute psychoactive effects using a quantitative measure, and reported on the relationship between acute effects and treatment outcome. We included 21 studies, involving 891 patients. Seventeen studies assessed patients with depression (TRD [k = 14]), three assessed substance use disorders, and one assessed social anxiety disorder. Overall, 41 associations were assessed, of which 26 % were significant. The studies reviewed displayed great variability in terms of methodology and quality of reporting. The most commonly assessed effect was dissociation, measured by the CADSS. Our results suggest that the CADSS total is not consistently associated with antidepressant outcomes. Apart from this, the current literature is too limited to draw definite conclusions on the presence of an association between acute psychoactive effects and mental health outcomes. The field would benefit from consistently employing a priori hypotheses, more transparent reporting and sufficiently powered statistical analyses. Furthermore, the use of a broader range of assessments tools of acute psychoactive effects during ketamine administration would be beneficial.

Familial Hypercholesterolaemia in a Bulgarian Population of Patients with Dyslipidaemia and Diabetes: An Observational Study.

INTRODUCTION: Patients with diabetes and familial hypercholesterolaemia (FH) are at very high risk of cardiovascular events, but rates of FH detection are very low in most countries, including Bulgaria. Given the lack of relevant data in the literature, we conducted a retrospective observational study to (1) identify individuals with previously undiagnosed FH among patients being treated at Bulgarian diabetes centres, and (2) gain insight into current management and attainment of low-density lipoprotein cholesterol (LDL-C) goals in such patients. METHODS: From a database of diabetes centres across Bulgaria we retrieved medical records from patients aged ≥ 18 years with type 1/2 diabetes mellitus (T1DM/T2DM) who were being treated with insulin/insulin analogues, dipeptidyl peptidase 4 inhibitors, glucagon-like peptide 1 receptor agonists and/or sodium-glucose co-transporter-2 inhibitors. Patients with FH (Dutch Lipid Clinic Network score ≥ 3) were identified, and their data analyzed (lipid-modifying therapy (LMT), diabetes treatment, cardiovascular events and glycaemic and lipid parameters). RESULTS: A total of 450 diabetic patients with FH (92.0% with T2DM; 52.4% receiving insulin/insulin analogues) were included in the analysis. LMT consisted of statin monotherapy (86% of patients; 18% receiving high-intensity statin monotherapy), statin-based combination therapy (13%) or fenofibrate (< 1%). Median LDL-C was 4.4 mmol/L. Although 30% of patients had a glycated haemoglobin level of ≤ 7%, only one patient (< 1%) achieved the LDL-C target recommended in 2016 European guidelines for very high-risk patients (< 1.8 mmol/L). Previous cardiovascular events were documented in 40% of patients. CONCLUSION: To our knowledge, this is the first study to specifically explore lipid target achievement in diabetic patients with FH. In this preselected Bulgarian population, < 1% of patients achieved the 2016 European guideline-defined LDL-C target. These data highlight the importance of identifying FH in diabetic patients as early as possible so that they can receive appropriate treatment.

Increased prevalence of depression and anxiety among subjects with metabolic syndrome and known type 2 diabetes mellitus - a population-based study.

OBJECTIVES: The metabolic syndrome (MetS) is a cluster of cardiovascular risk factors associated with high cardiovascular morbidity and mortality. The MetS and its elements have been linked to anxiety and depressive disorders. The aim of the current cross-sectional study was to assess the prevalence of depression and anxiety, measured by the Zung Self-Rating Scale in subjects with and without the metabolic syndrome and diabetes. METHODS: A total of 2111 adults were included, 1155 female, age 47.6 (13.7) and 956 male, age 45.2 (13.5). All participants filled questionnaires covering current and past disorders and medication, smoking and family history. Zung self-rating depression and anxiety scales were completed. Body weight, height and waist circumference were measured, BMI was calculated, serum glucose and lipids were measured. RESULTS: Depression (SDSi) and anxiety scores (SASi) were higher in the females and increased with age (p < 0.001). SDSi was higher in the females and males with metabolic syndrome (MetS) (50.9 ± 9.8 vs. 45.9 ± 8.9, p < 0.001 and 42.7 ± 9.2 vs. 40.5 ± 7.9 p < 0.001, respectively). SASi was higher in the MetS subjects (females 50.59 ± 11.35 vs. 45.97 ± 10.58, p < 0.001; males 40.48 ± 10.1 vs. 38.04 ± 8.42, p < 0.001). Both SDSi and SASi were higher in the subjects with known diabetes than in those with normal glucose tolerance (Mann-Whitney both p < 0,001). Positive depressive scores were more prevalent in subjects with MetS than those without (females 54% vs. 31.6%, p < 0.001; males 22.7% vs. 12.3%, p < 0.001). Depression and anxiety were more prevalent in the subjects with known diabetes than in those with normal glucose tolerance but not in the newly-diagnosed diabetes. The OR for depressiveness was 2.0 (1.3; 2.6) in subjects with MetS and 4.2 (2.3; 7.8) in those with known diabetes. CONCLUSIONS: In conclusion, depressiveness and anxiety were associated positively with age and female gender and were more prevalent among subjects with MetS and known diabetes mellitus.

Differences in the prevalence of vitamin D deficiency and hip fractures in nursing home residents and independently living elderly

ABSTRACT Objective To compare the prevalence of vitamin D deficiency and fracture history in nursing home residents and community-dwelling elderly subjects and to explore the association of vitamin D levels with various characteristics. Materials and methods Sixty-six nursing home residents and 139 community-dwelling elderly subjects participated. Marital status, medical history, medication including vitamin D supplements, smoking, past fractures were assessed. Weight and height were measured and body mass index calculated. Serum 25-hydroxyvitamin D (25-OHD), PTH, Ca, phosphate, creatinine and eGFR were determined. Results In the nursing home residents 25-OHD was lower (17.8 nmol/l, [9.4-28.6] vs. 36.7 nmol/l, [26.9-50], p < 0.001), PTH was higher (5.6 pmol/l, [3.9-8.9] vs. 4.7 pmol/l [3.6-5.8], P = 0.003) and 25-OHD deficiency was more prevalent (65.2% [53.7-76.7] vs. 22.3% [15.4-29.2], p < 0.001) as was elevated PTH (23% [12.8-33] vs. 5.8% [2-10], p = 0.001). 25-OHD correlated negatively with PTH (institutionalized r = -0.28, p = 0.025 and community-dwelling r = -0.36, p < 0.001). Hip fractures were reported by 8% of the residents and 2% of the independent elderly. The only predictor for hip fracture was elevated PTH (OR = 7.6 (1.5-36.9), p = 0.013). Conclusion The prevalence of vitamin D deficiency and secondary hyperparathyroidism was high in the institutionalized subjects. Hip fracture risk was associated with elevated PTH and not directly with vitamin D levels or the residency status.

Differences in the prevalence of vitamin D deficiency and hip fractures in nursing home residents and independently living elderly.

OBJECTIVE: To compare the prevalence of vitamin D deficiency and fracture history in nursing home residents and community-dwelling elderly subjects and to explore the association of vitamin D levels with various characteristics. MATERIALS AND METHODS: Sixty-six nursing home residents and 139 community-dwelling elderly subjects participated. Marital status, medical history, medication including vitamin D supplements, smoking, past fractures were assessed. Weight and height were measured and body mass index calculated. Serum 25-hydroxyvitamin D (25-OHD), PTH, Ca, phosphate, creatinine and eGFR were determined. RESULTS: In the nursing home residents 25-OHD was lower (17.8 nmol/l, [9.4-28.6] vs. 36.7 nmol/l, [26.9-50], p < 0.001), PTH was higher (5.6 pmol/l, [3.9-8.9] vs. 4.7 pmol/l [3.6-5.8], P = 0.003) and 25-OHD deficiency was more prevalent (65.2% [53.7-76.7] vs. 22.3% [15.4-29.2], p < 0.001) as was elevated PTH (23% [12.8-33] vs. 5.8% [2-10], p = 0.001). 25-OHD correlated negatively with PTH (institutionalized r = -0.28, p = 0.025 and community-dwelling r = -0.36, p < 0.001). Hip fractures were reported by 8% of the residents and 2% of the independent elderly. The only predictor for hip fracture was elevated PTH (OR = 7.6 (1.5-36.9), p = 0.013). CONCLUSION: The prevalence of vitamin D deficiency and secondary hyperparathyroidism was high in the institutionalized subjects. Hip fracture risk was associated with elevated PTH and not directly with vitamin D levels or the residency status.

Changes in the prevalence of diabetes mellitus in bulgaria (2006-2012).

AIM: The aim of this study was to compare two nationwide cross-sectional studies of diabetes prevalence in Bulgaria (2006 and 2012) and to assess its dynamics. MATERIAL AND METHODS: The two studies included 2396 and 2033 subjects, respectively. The International Diabetes Federation (IDF) diagnostic criteria were applied, and the data were weighed for type of settlement and age. RESULTS: Diabetes prevalence was found to be 7.9% in 2006 and 9.55% in 2012, P = 0.06, showing an increase of 20.9%. The absolute increase was 0.9% in the females and 2.3% in the males (P < 0.09). The increase was the largest in those aged 50-59: [9.4%, 2006 vs. 15.7%, 2012, P < 0.01]. Diabetes prevalence increased in the 20-60-year olds by 6.8% and decreased in the elderly by 6.1%. Obesity increased from 26.7 to 32.7%, P < 0.02. CONCLUSIONS: A significant increase in diabetes prevalence was found that necessitates healthcare measures and resources for community-based awareness and prevention programs.

The prevalence of the metabolic syndrome increases through the quartiles of thyroid stimulating hormone in a population-based sample of euthyroid subjects / Prevalência de síndrome metabólica aumenta em quartis de hormônio tireoestimulante em uma amostra de sujeitos eutiroides baseada na população

Objective The aim of the study was to assess the prevalence and characteristics of metabolic syndrome (MetS) and its elements in relation to TSH in euthyroid subjects. Materials and methods In the cross-sectional study, 2,153 euthyroid adults, 47.2 ± 14.5 years (20-94) with no current antithyroid or thyroid replacement therapy were enrolled. All participants filled a questionnaire on past and current morbidities, medication and smoking. Body weight, height, waist circumference, serum TSH, glucose and lipids were measured. The subjects were stratified by quartiles of TSH (QTSH) and the prevalence of the MetS elements was calculated. MetS was determined by the IDF 2005 criteria. Results Overweight prevalence was 37.2% (35.2-39.2), obesity in 25.1% (23.3-26.9), abdominal obesity – 61.4% (59.3-63.5), hypertension – 42.1% (38.9-43.1), diabetes/increased fasting glucose – 13.6% (12.1-15), low HDL-cholesterol – 27.6% (25.7-29.5), hypertriglyceridemia – 24.1% (22.3-25.9), MetS – 32.2% (30.2-34.2). MetS was more prevalent in the highest QTSH (34.9%, 30.9-38.9) than the lowest (27%, 23.3-30.9), p < 0.001, as were low HDL-C (32%, 28-35.9 vs. 25%, 21.3-28.7, p < 0.001) and hypertriglyceridemia (26.8%, 23-30.5 vs. 20.4%, 17-23.8, p = 0.015). Each QTSH increased the risk of MetS by 14%, p < 0.001, of hypertriglyceridemia by 20%, p = 0.001 and of low LDL-C by 9%, p = 0.042. Other significant factors for MetS were age, male gender and obesity. Conclusion The prevalence of MetS increased with higher QTSH within the euthyroid range, mostly by an increase in the dyslipidemia. Arq ...

Objetivo O objetivo deste estudo foi avaliar a prevalência e características da síndrome metabólica (MetS) e seus elementos em relação ao TSH em sujeitos eutireoides. Materiais e métodos Foram analisados, em um estudo transversal, 2.153 adultos eutiroides, de 47,2 ± 14,5 anos (20-94) sem terapia antitiroidiana ou de reposição. Todos os participantes preencheram um questionário sobre doenças atuais e passadas, medicações e tabagismo. O peso corporal, altura, circunferência da cintura, TSH, glicose e lipídios séricos foram medidos. Os sujeitos foram estratificados em quartis de TSH (QTSH) e a prevalência dos elementos da MetS foram calculados. Os critérios da MetS foram determinados pela IDF 2005. Resultados A prevalência de sobrepeso foi de 37,2% (35,2-39,2), de obesidade – 25,1% (23,3-26,9), obesidade abdominal – 61,4% (59,3-63,5), hipertensão – 42,1% (38,9-43,1), diabetes/aumento da glicose de jejum – 13,6% (12,1-15), baixo colesterol HDL – 27,6% (25,7-29,5), hipertrigliceridemia – 24,1% (22,3-25,9), MetS – 32,2% (30,2-34,2). A MetS foi mais prevalente no QTSH mais alto (34,9%; 30,9-38,9) do que no mais baixo (27%; 23,3-30,9), p < 0,001, assim como o baixo HDL-C (32%, 28-35,9 contra 25%, 21,3-28,7; p < 0,001) e hipertrigliceridemia (26,8%; 23-30,5 contra 20,4%, 17-23,8; p = 0,015). Cada QTSH aumentou o risco MetS em 14%, p < 0,001, de hipertrigliceridemia em 20%, p = 0,001 e de baixo LDL-C em 9%, p = 0,042. Outros fatores significativos para a MetS foram idade, sexo masculino e obesidade. ...

Age and menopausal status affect osteoprotegerin and osteocalcin levels in women differently, irrespective of thyroid function.

UNLABELLED: Osteoprotegerin (OPG) and osteocalcin (OC) are essential bone proteins. Recent studies have demonstrated that they are not secreted solely by bone cells; they play roles in the vascular function and energy metabolism, and they are influenced by multiple factors. The aim of the current study was to investigate the influence of menopause and age on OPG and OC in women with different thyroid-stimulating hormone (TSH) levels. MATERIAL AND METHODS: We studied 49 women with elevated TSH, 26 with suppressed TSH, and 67 age-matched euthyroid controls. Of them 64 were menstruating and 78 postmenopausal. Body weight, height, waist circumference (WC), body mass index (BMI), serum TSH, free thyroxin (FT4), OPG, and OC were measured. RESULTS: Generally, both OPG and OC were higher in the postmenopausal women than in the menstruating subjects (OPG 3.85 ± 1.49 pmol/L vs. 5.84 ± 2.42 pmol/L, P < 0.001; OC 8.84 ± 3.70 ng/dL vs. 12.87 ± 6.45 ng/dL, P < 0.001), and within the two thyroid dysfunction subgroups and the controls (all P < 0.05). OPG correlated with age (postmenopausal rho = 0.57, P < 0.001; premenopausal rho = 0.31, P = 0.015). Among the premenopausal subjects, OPG was higher in those with low TSH than in the controls (P = 0.048). OC correlated negatively with BMI and WC in the postmenopausal group (Spearman rho = -0.25, P = 0.03 and rho = -0.42, P < 0.001 respectively). OC was higher in the postmenopausal subjects with low TSH than in those with elevated TSH (P = 0.024), and correlated positively with FT4 (rho = 0.40, P = 0.002) and negatively with TSH (rho = -0.29, P = 0.013). CONCLUSIONS: In women, OPG and OC depended differently on age and menopause and, to a lesser extent, on the thyroid function and body composition.