Trust of Italian healthcare professionals in COVID-19 (anti-SARS-COV-2) vaccination.

ABSTRACT: Background. Vaccination is one of the most effective tools available to Public Health. Its potential usefulness is threatened by the rise of vaccine hesitancy among the general population, which has grown as much as to prompt the World Health Organization to express its concerns on the matter. The risk posed by vaccine hesitancy is even more concerning in the light of the efforts to curb the ongoing COVID-19 pandemic, which focus mainly on mass vaccination campaigns. This holds especially true when applied to healthcare professionals, among whom vaccine hesitancy can be particularly detrimental. For these reasons, our study focuses on potential determinants of vaccine hesitancy among healthcare professionals. Study design. The study is a cross-sectional study. Methods. Data were collected from January 1st to February 16th, by means of a self-administered online questionnaire in a cohort of Italian healthcare professionals. Results. Overall, 10,898 questionnaires were collected. Among the respondents, 1.1% expressed vaccine hesitancy. Hesitancy was less frequent in professionals involved in Primary Care and in the Clinical Scien-ces/Public Health group. Among clinicians, paediatricians, oncologists, and geriatrists showed especially accepting attitudes towards vaccination. Lower hesitancy rates were also registered among the respondents who already had received influenza vaccination and who never had any adverse effects following vaccination. Higher hesitancy rates were observed among individuals who had family members aged >65 years and with a history of severe adverse reactions to vaccination. Conclusion. Vaccine hesitancy rates were extremely low among participants in our study. Some medical specialties shown were particularly accepting towards vaccination. The potential predictors and protective factors pointed out by our analysis might allow more refined targets.

COVID-19 Vaccine Hesitancy and Early Adverse Events Reported in a Cohort of 7,881 Italian Physicians.

Background: The COVID-19 vaccination campaign began in Italy at the end of December 2020, with the primary aim of immunizing healthcare professionals, using the EMA approved mRNA vaccines (Comirnaty® by Pfizer/BioNTech; mRNA-1273 by Moderna) and recombinant adenoviral vaccine (Vaxzevria® by AstraZeneca). The study aimed at evaluating the prevalence and motivations underlying Vaccine Hesitancy, as well as the incidence and type of adverse events associated with COVID-19 vaccination. Methods: Cross-sectional study. Data were collected January 1st to 28th 2021 using a purposely created online self-administered questionnaire from a selected cohort of Italian physicians. Results: Overall, 7,881 questionnaires were analyzed: 6,612 physicians had received one dose, and 1,670 two doses of Comirnaty®; 30 had received one dose of mRNA-1273. Vaccine Hesitancy rate was 3.6%; it correlated with prior SARS-CoV-2 infection, diabetes, Adverse Eventss at previous vaccinations and refusal of 2020 flu vaccine, and was mainly motivated by concerns about vaccine Adverse Events. Typical Adverse Events were pain/itching/paresthesia at the inoculation site, followed by headache, fever, fatigue and myalgia/arthralgia occurring more frequently after the second dose (77.8 vs 66.9%; p<0.001), and in subjects with a prior SARS-CoV-2 infection. Conclusion: Adherence to COVID-19 vaccination is high among physicians. Adverse Events are typically mild and more frequent in people with a prior SARS-CoV-2 infection.

Increased prevalence of impulse control disorder symptoms in endocrine diseases treated with dopamine agonists: a cross-sectional study.

INTRODUCTION: Impulse control disorders (ICDs) have been described as a side effect of dopamine agonists (DAs) in neurological as well as endocrine conditions. Few studies have evaluated the neuropsychological effect of DAs in hyperprolactinemic patients, and these have reported a relationship between DAs and ICDs. Our objective was to screen for ICD symptoms in individuals with DA-treated endocrine conditions. MATERIALS AND METHODS: A cross-sectional analysis was conducted on 132 patients with pituitary disorders treated with DAs (DA exposed), as well as 58 patients with pituitary disorders and no history of DA exposure (non-DA exposed). Participants responded to the full version of the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's disease (QUIP). RESULTS: Compared with the non-DA-exposed group, a higher prevalence of DA-exposed patients tested positive for symptoms of any ICD or related behavior (52% vs. 31%, p < 0.01), any ICD (46% vs. 24%, p < 0.01), any related behavior (31% vs. 17%, p < 0.05), compulsive sexual behavior (27% vs. 14%, p < 0.04), and punding (20% vs. 7%, p < 0.02) by QUIP. On univariate analysis, DA treatment was associated with a two- to threefold increased risk of any ICD or related behavior [odds ratio (OR) 2.43] and any ICD (OR 2.70). In a multivariate analysis, independent risk factors for any ICD or related behavior were DA use (adjusted OR 2.22) and age (adjusted OR 6.76). Male gender was predictive of the risk of hypersexuality (adjusted OR 3.82). DISCUSSION: Despite the QUIP limitations, a clear sign of increased risk of ICDs emerges in individuals with DA-treated pituitary disorders. Our data contribute to the growing evidence of DA-induced ICDs in endocrine conditions.

Results and predictors of outcome of endoscopic endonasal surgery in Cushing's disease: 20-year experience of an Italian referral Pituitary Center.

PURPOSE: To assess outcomes and predictors of early and long-term remission in patients with Cushing's disease (CD) due to ACTH-secreting adenomas treated via endoscopic endonasal approach (EEA). METHODS: This is a retrospective study. Consecutive patients operated for CD from 1998 to 2017 in an Italian referral Pituitary Center were enrolled. Clinical, radiological, and histological data at enrollment and follow-up were collected. RESULTS: 151 patients (107 F) were included; 88.7% were naïve for treatment, 11.3% had been treated surgically and 11.2% medically. At pre-operative magnetic resonance imaging (MRI), 35 had a macroadenoma and 80 a microadenoma, while tumor was undetectable in 36 patients. Mean age at surgery was 41.1 ± 16.6 years. Diagnosis was confirmed histologically in 82.4% of the cases. Patients with disease persistence underwent second surgery and/or medical and/or radiation therapy. Mean follow-up was 92.3 ± 12.0 (range 12-237.4) and median 88.2 months. Remission rate was 88.1% after the first surgery and 90.7% at last follow-up. One patient died of pituitary carcinoma. Post-surgical cortisol drop (p = 0.004), tumor detection at MRI (p = 0.03) and size < 1 cm (p = 0.045) increased the chance of disease remission; cavernous sinus invasion was a negative predictor of outcome (p = 0.002). Twenty-seven patients developed diabetes insipidus and 18 hypopituitarism. Surgery repetition increased the risk of hypopituitarism (p = 0.03), but not of other complications, which included epistaxis (N = 2), cerebrospinal fluid leakage (1), pneumonia (3), myocardial infarction (1), and pulmonary embolisms (2). CONCLUSIONS: Selective adenomectomy via EEA performed by experienced surgeons, supported by a multidisciplinary dedicated team, allows long-term remission in the vast majority of CD patients with low complication rate.

An update on heart disease risk associated with testosterone boosting medications.

INTRODUCTION: The cardiovascular (CV) safety of testosterone replacement therapy (TRT) remains a crucial issue in the management of subjects with late-onset hypogonadism. The authors systematically reviewed and discussed the available evidence focusing our analysis on heart-related issues. AREAS COVERED: All the available data from prospective observational studies evaluating the role endogenous T levels on the risk of acute myocardial infarction (AMI) were collected and analyzed. In addition, the impact of TRT on heart-related diseases, as derived from pharmaco-epidemiological studies as well as from randomized placebo-controlled trials (RCTs), was also investigated. EXPERT OPINION: Available evidence indicates that endogenous low T represents a risk factor of AMI incidence and its related mortality. TRT in hypogonadal patients is able to improve angina symptoms in subjects with ischemic heart diseases and exercise ability in patients with heart failure (HF). In addition, when prescribed according to the recommended dosage, TRT does not increase the risk of heart-related events.

Arthropathy in acromegaly: a questionnaire-based estimation of motor disability and its relation with quality of life and work productivity.

PURPOSE: Arthropathy is a common and disabling complication of acromegaly. Since in this condition radiological findings rarely correspond to functional impairment, we elected to quantify in a large cohort of acromegalic patients: the degree of motor disability compared with data from general population, the impact of joint involvement on quality of life and work productivity, and to look for associated factors. METHODS: In 211 acromegalic patients, 131 with controlled disease and 80 with active disease, eight validated scales were used to evaluate the (i) prevalence and distribution of arthropathy, (ii) degree of motor disability and joint symptoms (VAS, AIMS symptoms and WOMAC), (iii) quality of life (AcroQoL and PASQ) and work capability (WPAI:GH) as consequences of joint complications. RESULTS: Using the WOMAC questionnaire, for which population based normative values are available, a significantly higher prevalence and severity of motor disability was detected in acromegalics compared to the general population from literature. The results provided by the different questionnaires turned out to be highly concordant. All measures of motor disability correlated both with impaired quality of life and motor disability and were worse in females and in patients with higher BMI. CONCLUSIONS: The questionnaires VAS, AIMS symptoms, and WOMAC (this latter both as a whole and with its functionality subscale), with their scores, proved to be the most adequate tools to evaluate motor disability and its consequences on both quality of life and work productivity in acromegaly. Female gender and higher BMI are associated with worse articular symptoms.

Comparative assessment of hypothalamic-pituitary-adrenal axis suppression secondary to intrabursal injection of different glucocorticoids: a pilot study.

BACKGROUND: Hypothalamic-pituitary-adrenal axis (HPAA) suppression is the most common and dangerous, although often unrecognized and untreated, side effect of glucocorticoid administration. The risk and duration depend both on patient and treatment characteristics. High-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) currently represents the gold standard method to evaluate the metabolism of endogenous and exogenous steroids. OBJECTIVE: To assess prevalence, severity, and duration of HPAA suppression subsequent to the injection of two steroids with equivalent potency but different pharmacokinetics. SUBJECTS AND METHODS: Single-blind randomized case-control pilot study. Forty patients (22 F; age 48.7 ± 7.2 years) with shoulder calcific tendinopathy received an intrabursal injection of 40 mg of 6α-methylprednisolone acetate (MA) or triamcinolone acetonide (TA). Just before (T0) and after 1 (T1), 7 (T2), 15 (T3), 30 (T4) and 45 (T5) days, we assessed morning blood cortisol and ACTH by RIA, and 24-h urinary levels of MA, TA and free cortisol by HPLC-MS/MS. RESULTS: HPAA function was normal at baseline. At T1, all patients presented HPAA suppression reaching the lowest cortisol, ACTH and UFC levels, that were similar between groups. At T2, mean cortisol remained lower than at baseline (p < 0.0001) in the TA group. In both groups, mean cortisol and ACTH levels progressively normalized, suggesting HPA recovery, except for three patients in the MA and two in the TA group. UFC levels remained lower than normal (p < 0.0001) up to T5, despite the disappearance of exogenous GCs. No patient developed manifestations of hypocortisolism. CONCLUSIONS: A single 40-mg intrabursal injection of MA or TA is sufficient to suppresses HPAA up to 45 days. Although typically asymptomatic, patients should be instructed to recognize and report symptoms suggestive for hypocortisolism, to provide prompt diagnosis, and eventually, treatment, thus avoiding severe complications.

Validation of a clinicopathological score for the prediction of post-surgical evolution of pituitary adenoma: retrospective analysis on 566 patients from a tertiary care centre.

Objective and design A clinicopathological score has been proposed by Trouillas et al. to predict the evolution of pituitary adenomas. Aim of our study was to perform an independent external validation of this score and identify other potential predictor of post-surgical outcome. Methods The study sample included 566 patients with pituitary adenomas, specifically 253 FSH/LH-secreting, 147 GH-secreting, 85 PRL-secreting, 72 ACTH-secreting and 9 TSH-secreting tumours with at least 3-year post-surgical follow-up. Results In 437 cases, pituitary adenomas were non-invasive, with low (grade 1a: 378 cases) or high (grade 1b: 59 cases) proliferative activity. In 129 cases, tumours were invasive, with low (grade 2a: 87 cases) or high (grade 2b: 42 cases) proliferative activity. During the follow-up (mean: 5.8 years), 60 patients developed disease recurrence or progression, with a total of 130 patients with pituitary disease at last follow-up. Univariate analysis demonstrated a significantly higher risk of disease persistence and recurrence/progression in patients with PRL-, ACTH- and FSH/LH-secreting tumours as compared to those with somatotroph tumours, and in those with high proliferative activity (grade 1b and 2b) or >1 cm diameter. Multivariate analysis confirmed tumour type and grade to be independent predictors of disease-free-survival. Tumour invasion, Ki-67 and tumour type were the only independent prognostic factors of disease-free survival. Conclusions Our data confirmed the validity of Trouillas' score, being tumour type and grade independent predictors of disease evolution. Therefore, we recommend to always consider both features, together with tumour histological subtype, in the clinical setting to early identify patients at higher risk of recurrence.

Characterization and implications of thyroid dysfunction induced by immune checkpoint inhibitors in real-life clinical practice: a long-term prospective study from a referral institution.

PURPOSE: Autoimmune diseases are typically associated with immune checkpoints blockade. This study aims at assessing, in real-life clinical practice, the prevalence and impact of thyroid disorders induced by immune checkpoint inhibitors. METHODS: 52 patients (30 F; age 61 ± 13 years) with advanced melanoma treated with ipilimumab (3 mg/kg i.v./3 weeks; 4 doses) were included. For disease progression, 29 (16 F) of them received nivolumab (3 mg/kg i.v./2 weeks) or pembrolizumab (2 mg/kg i.v./3 weeks). Thyroid function and autoimmunity were assessed before, after 6 weeks, at the end of ipilimumab, as well as before and every 3 months during nivolumab/pembrolizumab treatment. RESULTS: During ipilimumab, 7 (4 F) patients developed thyroid dysfunction (4 thyroiditis, 1 associated with hypothyroidism; 2 thyrotoxicosis in a previously euthyroid multinodular goiter; 1 hypothyroidism worsened). During PD1 inhibitors, 7 patients (3 F) developed hypothyroidism with severe manifestations in 6 of them; 3 patients suffered from euthyroid autoimmune thyroiditis from baseline, one after ipilimumab; 2 patients developed after transient thyrotoxicosis. Mean follow-up after anti-CTLA4 inhibitors treatment was 36 ± 28 months. Thyroid disorders occurred 45.1 ± 20.8 and 151 ± 67 days after the initiation of CTLA4 and PD1 inhibitors, respectively. Autoimmune disorders and BRAF mutation were associated with a better clinical response to CTLA4 followed by PD1 treatment. CONCLUSIONS: Immune checkpoint blockade is burdened by a high incidence of autoimmune thyroid dysfunction, which is often severe. Therefore, early and careful monitoring and, eventually, treatment are crucial to prevent the negative impact of thyroid dysfunction on the clinical outcome.

Effectiveness of educational and lifestyle interventions to prevent paediatric obesity: systematic review and meta-analyses of randomized and non-randomized controlled trials.

OBJECTIVE: This review and meta-analysis aim at updating a previous meta-analysis carried out by Waters et al. on the efficacy of interventions aimed at preventing childhood obesity and at identifying predictors of outcome. METHODS: Using an ad-hoc search string, PubMed database was searched for studies assessing body mass index reduction associated with programmes lasting ≥12 weeks in overweight and obese children aged 2-18 years. Studies designed for children with eating disorders or relevant comorbidities were excluded. Studies meeting inclusion criteria were classified according to patient age (<6, 6-12 and 13-18 years), and intervention type (physical activity, diet or both), setting (educational, family or both) and duration (≤1 or >1 year). The search was also extended to other databases. Hand-searching techniques were also applied. The Cochrane 'risk of bias' was applied for quality assessment. RESULTS: Seventy-two studies were meta-analysed. Overall, the best results were achieved by programmes combining diet and physical activity (n = 39). With regard to the setting, programmes involving both school and family and lasting ≤1 year were the most efficacious for 6- to 12-year-old children (n = 26); family-based-only interventions were also effective in children <6 years old (n = 2), although results have to be interpreted cautiously because of the small number of patients enrolled and the high study heterogeneity. In 13- to 18-year-old patients, interventions delivered at school (n = 8) were substantially unsuccessful. CONCLUSIONS: Interventions for childhood obesity prevention should include both diet and physical activity, be preferentially targeted towards school age children and involve both the school and family setting. However, because of the important methodological limitations associated with currently available literature, additional studies are needed to draw definite conclusions.

Usefulness of an ad hoc questionnaire (Acro-CQ) for the systematic assessment of acromegaly comorbidities at diagnosis and their management at follow-up.

PURPOSE: To determine the validity of a self-administered questionnaire (Acro-CQ) developed to systematically assess the presence, type and time of onset of acromegaly comorbidities. METHODS: This is a cross-sectional study; 105 acromegaly patients and 147 controls with other types of pituitary adenoma, referred to a specialized Italian Center, autonomously compiled Acro-CQ in an outpatient clinical setting. To test its reliability in a different setting, Acro-CQ was administered via mail to 78 patients with acromegaly and 100 with other pituitary adenomas, referred to a specialized US Center. Data obtained from questionnaires in both settings were compared with medical records (gold standard). RESULTS: Demographics of patients and controls from both countries were similar. In both settings, >95 % of the questionnaires were completely filled; only one item was missed in the others. Concordance with medical record was excellent (k > 0.85) for most of the items, independently from the way of administration, patient age, gender and nationality, pituitary adenoma type and disease activity. CONCLUSIONS: Acro-CQ is an inexpensive, highly accepted from patients and reliable tool recommended to expedite systematic collection of relevant clinical data in acromegaly at diagnosis, to be replicated at follow-ups. This tool may guide a targeted, cost-effective management of complications. Moreover, it could be applied to retrieve data for survey studies in both acromegaly and other pituitary adenomas, as information is easily and rapidly accessible for statistical analysis.