Management of Hypothyroidism in Internal Medicine: Patient Profile and Effects of an Educational Programme in the Cluster-Randomized FADOI TIAMO Study.

Background and aims: There is still limited knowledge regarding the clinical profile and appropriateness of treatment in patients with hypothyroidism hospitalized in Internal Medicine (IM) Departments in Italy. The aim of this study is to evaluate: 1) the characteristics of patients and possible deviations from national and international clinical practice recommendations (CPRs) in evidence-based guidelines (EBGs); 2) the improvement of patient management by means of a standardized educational programme (EP). Methods: A nationwide multicentre study, comprising two replications of a retrospective survey (phases 1 and 3) with an intervening EP (phase 2) in half of the centres and no EP in the other half, was conducted. The EP was based on outreach visits. Centres were assigned to the two arms of the study, labelled the training group (TG) and control group (CG) respectively, by cluster randomization. Four EBGs and 39 CPRs provided the basis on which 22 treatment management indicators were identified (7 referring to the time of hospital admission, 15 to post-admission). Results: The 21 participating centres recruited 587 hospitalized patients with hypothyroidism, 421 of which were females (71.7%, mean age 74.1 + 14.4 yrs): 318 in phase 1 and 269 in phase 3. The cause of hypothyroidism was unknown in 282 patients (48%). Evaluation at the time of admission identified satisfactory adherence to CPRs (>50%) for 63.6% of the indicators. In the phase 3, TG centres showed significant improvement vs CG in 4 of the 15 post-admission indicators, while 1 out of 15 was significantly worse. Conclusions: The EP based on outreach visits significantly improved some indicators in the management of patients with hypothyroidism, with specific reference to appropriateness of TSH dosage and levothyroxine (LT4) treatment modality. Clinical Trial Registration: ClinicalTrials.gov, identifier NCT05314790.

TSH evaluation in hypothyroid patients assuming liquid levothyroxine at breakfast or 30 min before breakfast.

PURPOSE: To compare TSH levels of hypothyroid patients treated with liquid LT4 at breakfast or 30 min before breakfast. PATIENTS AND METHODS: Subjects, aged 18-75 years old, were eligible if they presented hypothyroidism, due to Hashimoto's thyroiditis or after thyroidectomy for proven benign goiter. Seven hundred ninety-eight patients were recruited and enrolled in the study. Thirty-seven subjects withdrew from the trial. A total of 761 patients (mean age 46.2 ± 10.8 years) completed the study. The starting dose of LT4 was determined through clinical judgment, taking into account TSH levels, estimated residual thyroid function, age, body weight and comorbidities. All patients underwent TSH, fT4, and fT3 evaluation to verify achievement of euthyroidism with their initial fasting state assumption of LT4 after 8 weeks of therapy. If euthyroidism was not achieved, an appropriately adjusted LT4 dose was administered for 8 weeks, after which thyroid function parameters were checked again. If euthyroidism was achieved, the patients were asked to take LT4 at breakfast and hormone levels were checked again after 6 months. RESULTS: At the end of the study period, no significant differences in serum TSH level were observed whether LT4 was ingested at breakfast or 30 min prior in a fasting state: 2.61 ± 1.79 vs. 2.54 ± 1.86 mIU/L, respectively (p = 0.455). CONCLUSIONS: This study confirms in a large set of patients that a liquid LT4 formulation can be taken directly at breakfast and potentially improve therapeutic compliance.

The basal to total insulin ratio in outpatients with diabetes on basal-bolus regimen.

OBJECTIVE: To evaluate the basal/total ratio of daily insulin dose (b/T) in outpatients with diabetes type 1 (DM1) and type 2 (DM2) on basal-bolus regimen, by investigating whether there is a relationship with HbA1c and episodes of hypoglycemia. METHODS: Multicentric, observational, cross-sectional study in Italy. Adult DM1 (n = 476) and DM2 (n = 541) outpatients, with eGFR >30 mL/min/1.73 m2, on a basal-bolus regimen for at least six months, were recruited from 31 Italian Diabetes services between March and September 2016. Clinicaltrials.govID: NCT03489031. RESULTS: Total daily insulin dose was significantly higher in DM2 patients (52.3 ± 22.5 vs. 46 ± 20.9 U/day), but this difference disappeared when insulin doses were normalized for body weight. The b/T ratio was lower than 0.50 in both groups: 0.46 ± 0.14 in DM1 and 0.43 ± 0.15 in DM2 patients (p = 0.0011). The b/T was significantly higher in the patients taking metformin in both groups, and significantly different according to the type of basal insulin (Degludec, 0.48 in DM1 and 0.44 in DM2; Glargine, 0.44 in DM1 and 0.43 in DM2; Detemir, 0.45 in DM1 and 0.39 in DM2). The b/T ratio was not correlated in either group to HbA1c or incidence of hypoglycemia (<40 mg/dL, or requiring caregiver intervention, in the last three months). In the multivariate analysis, metformin use and age were independent predictors of the b/T ratio in both DM1 and DM2 patients, while the type of basal insulin was an independent predictor only in DM1. CONCLUSION: The b/T ratio was independent of glycemic control and incidence of hypoglycemia.

Correction to: The basal to total insulin ratio in outpatients with diabetes on basal-bolus regimen.

[This corrects the article DOI: 10.1007/s40200-018-0358-2.].

Factors associated with autonomic nervous function in type 1 and type 2 diabetic subjects free of clinical manifestations of autonomic neuropathy.

Even though autonomic diabetic neuropathy is highly prevalent and a noted risk factor for cardiovascular morbidity and mortality, very little is known about factors associated with it. We carried out standard autonomic nervous system function tests by means of a computerized portable system on 55 diabetic patients (22 with type 1 diabetes, 33 with type 2 diabetes) who had no signs or symptoms of autonomic diabetic neuropathy and on 10 age- and sex-matched healthy control subjects. Test results of patients with type 1 diabetes did not differ significantly from those with type 2 diabetes. Of the clinical, metabolic, and anthropometric variables considered, only the duration of diabetes was inversely and independently correlated to deep breathing test scores (E:I ratio value of deep breathing 1.38-0.009. years of diabetes; R2 = 0.25). The duration of diabetes was inversely correlated to variations in orthostatic systolic blood pressure (r = -0.37, p < 0.01). The prevalence of diabetic retinopathy (score: 1 = no; 2 = yes) was significantly higher in the diabetic group with lower deep breathing values (1.8 +/- 0.3 vs 1.0 +/- 0.0; p < 0.01). The prevalence of ischemic electrocardiographic alterations (score: 1 = no; 2 = yes) was significantly higher in the diabetic group with a poorer orthostatic systolic blood pressure response (1.4 +/- 0.1 vs 1.2 +/- 0.1; p < 0.01). This study suggests that 1) autonomic neuropathy is correlated to disease duration; 2) type of diabetes, present level of metabolic compensation, and anthropometric characteristics do not seem correlated to this complication; 3) diabetic retinopathy and ischemic cardiopathy may be correlated to autonomic neuropathy.

[Ultrasonographic study of gallbladder kinetic activity in patients with motor-like dyspepsia]. / Lo studio ecografico dell'attività motoria della colecisti nei pazienti con dispepsia semil-motoria.

BACKGROUND AND METHODS: Forty-six subjects affected with functional dyspepsia (the coherence of illness was excluded by proper research) not classifiable, according to Drossman principles, into reflex-like or ulcer-like dyspepsia class have been studied. All the patients, asked about either the presence or the absence of any dyspeptic symptoms, with the only condition that the symptom indicated had been present at least for three months continuously, were subjected to abdominal ultrasonography and after-meal cholecystokinetic. The emptying of cholecyst has been monitored until 150 minutes after meal, at near intervals. As Control Group subjects have been used, free from dyspeptic symptomatology and superimposable by age, sex and alimentary habits to the patients of the Study Group. RESULTS: The authors observed a) that the initial cholecystic volume after 15 minutes was significantly (p<0.001) reduced in the patients with dyspeptic symptoms, compared with those of the Control Group; b) that there was not significant difference between the two groups at 30, 45, 60 minutes; c) that in the patients of the Control Group cholecyst had returned to its normal volume in 90-120 minutes while, in the Study Group it had kept its volume almost unchanged until 150 min after meal, with a highly significant difference between the two groups (p<0.001). From the clinic-symptomatologic point view, the authors have verified, besides the proper symptoms of motor-like dyspepsia, also other symptoms not indicated by other authors, and precisely ''after meal sleepiness'', ''bitter mouth'' and ''after meal cephalea'', in 41 to 63%. CONCLUSIONS: The authors suppose that in the patients with functional dyspepsia, not reflex-like or ulcer-like dyspepsia the kinetic disorder responsible for symptomatology is in any way related to a disorder of kinetic activity of cholecyst.

[Correlation between skinfold thickness and ultrasonography in the study of subcutaneous adipose tissue in females]. / Correlazione plicometria-ecografia nello studio dell'adipe sottocutaneo in soggetti di sesso femminile.

The aim of this study was to verify if there is a 1:2 correlation between subcutaneous adipose tissue thickness measured by ultrasonography and skinfold caliper and if this correlation varies in function of the degree of obesity, subcutaneous fat thickness, and the area evaluated. Forty women (age 27.9 +/- 11.7 years, body mass index 28.75 +/- 5.40 Kg/m2, waist to hip ratio 0.77 +/- 0.06) underwent ultrasonographic measurement of subcutaneous adipose tissue and skinfold caliper measurement at nine different sites (bicipital, tricipital, subscapular, suprailiac, epigastric umbilical, hypogastric, gluteal, and femoral). Data analysis confirmed a significant correlation between measurements made by ultrasonography and skinfold plicometry at all sites when the patients were not subdivided according to body mass index or skinfold thickness. When they were subdivided on the basis of body mass index, a significant correlation was found for subjects with a body mass index < 30; when the index was > 30, the correlation was observed at only the subscapular and suprailiac sites, and to a lesser degree at the tricipital and femoral sites. Moreover, a highly significant correlation was found only at sites at which ultrasonographic thickness was not > 20 mm (p < 0.001) with an r value decreasing progressively from 0.685 (thickness < 10 mm) to 0.248 (thickness > 40 mm). Given the great variability of this correlation, we suggest that ultrasonography is preferable to plicometry for the measurement of fat.

Correlation between digestive disease and psychiatric disease: casual or causal implication?

The aim of this study was to evaluate the prevalence of psychiatric disturbances among patients affected with digestive diseases (both organic and functional) and, viceversa, the prevalence of digestive disturbances among patients with psychiatric diseases. We performed a trasversal study on: 100 patients with organic digestive diseases and 100 patients with functional digestive diseases afferent from a Gastroenterologic Ambulatory (gastroenterologic group); 50 patients afferent from a Psychiatry Service (psychiatric group) and 50 patients afferent from a General Medicine Ambulatory affected with a non gastroenterologic active problem (control group). Each patient underwent an anamnestic, laboratory and instrumental evaluation, in order to ascertain or exclude the presence of digestive symptoms and their eventual organic basis; moreover, a semistructured interview was performed aimed at identifying a psychiatric disturbance, according to DSM-IIIr criteria. Our results showed a significantly higher prevalence: 1) of psychiatric disturbances, in the gastroentorologic group versus the control group (p<0.001), especially of somatoform (p<0.05) and anxious (p<0.001) disorders; 2) of psychiatric disturbances among patients affected by functional digestive disorders versus patients affected by organic digestive disorders; 3) of gastroenterologic disorders, in the psychiatric group versus the control group (p<0.001), with a significantly higher prevalence of functional gastroenterologic syndromes in comparison the organic ones (p<0.001). The well-established bidirectional correlation between digestive functional and psychiatric disorders is a necessary but not sufficient condition to state a relationship of direct causality between the two syndromes; however we can hypothesize that the well documented neuro-hormonal alterations may cause, on clinical grounds different symptoms, that are differently interpreted by the different specialists (gastroenterologists or psychiatrists) consulted.

Recognizing potential toxicity of phenol.

Data is presented which correlates phenol levels in human urine with inhalatory and skin exposures (phenol is rapidly collected and excreted in urine). "Normal" phenol levels in human urine are compared with urine levels resulting from exposure to phenol. A correlation is made between urine phenol levels and potential human toxicity.

Cadmium levels in hair and other tissues during continuous cadmium intake.

Rats that received cadmium 300 ppm in drinking water (average daily cadmium intake = 4.5 mg/rat) for 12 wk attained peak cadmium levels of 112, 34, and 19 mug/g in hair, liver, and kidney, respectively, at week 4. Rats that ingested cadmium 200 ppm (average daily cadmium intake = 3.6 mg/rat) for 13 wk attained peak cadmium levels of 29 mug/g in kidney at week 7, and 94 and 27 mug/g in hair and liver, respectively, at week 9. Despite continuous exposure to the heavy metal, tissue cadmium concentrations declined to steady-state levels of 24-33 mug/g in hair and 10-17 mug/g in liver and kidney. Histopathologic effects were not observed in liver or kidney. In contrast to cadmium in hair, blood cadmium levels, which remained consistently low (less than 0.04 mug/ml) throughout the study, did not correlate with changes in cadmium levels in liver and kidney.