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The Zoladex In Pre-menopausal Patients (ZIPP) study was designed to determine whether addition of goserelin (‘Zoladex’) and/or tamoxifen to adjuvant therapy (radiotherapy and/or chemotherapy), provided benefit to pre- or peri-menopausal women with operable, early breast cancer.

Abstract Background To evaluate outpatient healthcare expenditure associated with different levels of BMI and glucose metabolism alterations. Methods The study is based on a representative national sample of adults, with data obtained from electronic clinical records of 900 Italian general practitioners. Data relative to the year 2018 were analyzed. The study population was classified according to BMI (normal weight, overweight, and obesity classes 1, 2, and 3) and glucose metabolism status (normoglycemia – NGT; impaired fasting glucose – IFG; diabetes mellitus – DM). Outpatient health expenditures include diagnostic tests, specialist visits, and drugs. Results Data relative to 991,917 adults were analyzed. Annual per capita expenditure rose from 252.2 Euro among individuals with normal weight to 752.9 Euro among those with class 3 obesity. The presence of obesity determined an excess cost, particularly among younger individuals. Within each BMI class, the presence of IFG or DM2 identified subgroups of individuals with substantially higher healthcare expenditures. Conclusions Outpatient healthcare costs markedly increased with increasing BMI in all age categories, particularly among individuals below 65. Addressing the double burden of excess weight and hyperglycemia represents a significant challenge and a healthcare priority.

As online platforms grow, they find themselves increasingly trying to balance two competing priorities: individual rights and public health. This has coincided with the professionalization of platforms’ trust and safety operations—what we call the “customer service” model of online governance. As professional trust and safety teams attempt to balance individual rights and public health, platforms face a crisis of legitimacy, with decisions in the name of individual rights or public health scrutinized and criticized as corrupt, arbitrary, and irresponsible by stakeholders of all stripes. We review early accounts of online governance to consider whether the customer service model has obscured a promising earlier model where members of the affected community were significant, if not always primary, decision-makers. This community governance approach has deep roots in the academic computing community and has re-emerged in spaces like Reddit and special purpose social networks and in novel platform initiatives such as the Oversight Board and Community Notes. We argue that community governance could address persistent challenges of online governance, particularly online platforms’ crisis of legitimacy. In addition, we think community governance may offer valuable training in democratic participation for users.

Abstract Background An “obesity paradox” for mortality has been shown in chronic disorders such as diabetes, and attributed to methodological bias, including the use of body mass index (BMI) for obesity definition. This analysis investigated the independent association of BMI versus surrogate measures of central adiposity with all-cause mortality in individuals with type 2 diabetes. Methods The Renal Insufficiency And Cardiovascular Events Italian Multicentre Study is a prospective cohort study that enrolled 15,773 patients in 19 Italian centres in 2006–2008. Exposures were BMI and the surrogate measures of central adiposity waist circumference (WC), waist-to-height ratio (WHtR), and A Body Shape Index (ABSI). Vital status was retrieved on 31 October 2015 for 15,656 patients (99.3%), Results Age- and sex-adjusted hazard ratios and 95% confidence intervals were significantly higher in BMI-based underweight (1.729 [1.193–2.505), P = 0.004), moderately obese (1.214 [1.058–1.392), P = 0.006) and severely obese (1.703 [1.402–2.068), P

Background: We sought to describe global patterns in achievement of risk factor control for primary prevention in patients with T2D and explore the association of country's GNI/capita with risk factor control. Methods: The DISCOVER study is a prospective, observational study of patients with T2D from 38 countries enrolled at initiation of second-line glucose-lowering therapy. We examined achievement of risk factor control (glycosylated hemoglobin 0.08 for all). Interpretation: In a global, prospective study of patients with T2D, we found that cardiovascular risk factor control achievement was suboptimal despite 3 years of follow-up in specialized health care systems. Neither country-level nor patient-level socioeconomic factors fully explained this finding.

Summary: Background: A delay in reaching HbA1c targets in patients with newly-diagnosed type 2 diabetes (T2D) is associated with an increased long-term risk of developing cardiovascular diseases (CVD), a phenomenon referred to as legacy effect. Whether an early introduction of glucose-lowering drugs with proven benefit on CVD can attenuate this phenomenon is unknown. Methods: Using data derived from a large Italian clinical registry, i.e. the AMD Annals, we identified 251,339 subjects with newly-diagnosed T2D and without CVD at baseline. Through Cox regressions adjusted for multiple risk factors, we examined the association between having a mean HbA1c between 7.1 and 8% or >8%, compared with ≤7%, for various periods of early exposure (0–1, 0–2, 0–3 years) and the development of later (mean subsequent follow-up 4.6 ± 2.9 years) CVD, evaluated as a composite of myocardial infarction, stroke, coronary or peripheral revascularization, and coronary or peripheral bypass. We performed this analysis in the overall cohort and then splitting the population in two groups of patients: those that introduced sodium-glucose transport protein 2 inhibitors (SGLT-2i) during the exposure phase and those not treated with these drugs. Findings: Considering the whole cohort, subjects with both a mean HbA1c between 7.1 and 8% and >8%, compared with patients attaining a mean HbA1c ≤ 7%, showed an increased risk of developing the outcome in all the three early exposure periods assessed, with the highest risk observed in patients with mean HbA1c > 8% in the 3 years exposure period (hazard ratio [HR]1.33; 95% confidence interval [CI] 1.063–1.365). The introduction of SGLT-2i during the exposure periods of 0–1 and 0–2 years eliminated the association between poor glycemic control and the outcome (p for interaction 0.006 and 0.003, respectively, vs. patients with the same degree of glycemic control but not treated with these drugs). Interpretation: Among patients with newly diagnosed T2D and free of CVD at baseline, a poor glycemic control in the first three years after diagnosis is associated with an increased subsequent risk of CVD. This association is no longer evident when SGLT-2i are introduced in the first two years, suggesting that these drugs attenuate the phenomenon of legacy effect. An early treatment with these drugs might thus promote a long-lasting benefit in patients not attaining proper glycemic control after T2D diagnosis. Funding: This work was supported, in part, by the Italian Ministry of Health (Ricerca Corrente) to IRCCS MultiMedica.

Background: Familial chylomicronemia syndrome (FCS) is a rare inherited condition due to lipoprotein lipase deficiency, characterized by hyperchylomicronemia and severe hypertriglyceridemia. Diagnosis is often delayed, thus increasing the risk of acute pancreatitis and hospitalization. Hypertriglyceridemia is a common finding in patients with type 2 diabetes (T2D), who may harbor FCS among the most severe forms. Aim of the Study: We investigated the prevalence and clinical characteristics associated with severe hypertriglyceridemia in a range indicative of FCS, in a large population of subjects with T2D. Methods: Within the large population of the AMD Annals Initiative, patients with T2D with a lipid profile suggestive of FCS [triglycerides >880 mg/dL and/or high-density lipoprotein (HDL)-cholesterol <22 mg/dL or non-HDL-cholesterol ≤70 mg/dL] and their clinical features have been identified. Results: Overall, 8592 patients had triglyceride values >880 mg/dL in a single examination, 613 in two examinations, and 34 in three or more measurements. Patients with high triglyceride levels were mostly male (80%), with a relatively young age (54 years), short duration of diabetes (6.3 years), and elevated hemoglobin A1c (HbA1c) levels (9.4%). By stratifying this group of patients according to the severity of hypertriglyceridemia, more severe hypertriglyceridemia (triglyceride levels ≥2000 mg/dL) was associated with an even younger age (52 vs. 54 years), even higher mean HbA1c values (10.0% vs. 9.4%), and significantly higher HDL-cholesterol levels (37.9 vs. 32.4 mg/dL; P < 0.0001). Patients with persistently elevated triglyceride levels (n = 34), on three measurements, had a younger age; lower body mass index, HbA1c, and HDL-cholesterol levels; more frequent use of fibrates and insulin; and a higher prevalence of major cardiovascular events. Conclusions: Severe hypertriglyceridemia is a frequent condition in outpatients with T2D participating in the AMD Annals Initiative, and it is associated with male sex, young age, short disease duration, and a worse glycemic profile. Among patients with persistent severe hypertriglyceridemia, hidden FCS may be present. [ABSTRACT FROM AUTHOR]

Aim: To compare the effectiveness of different basal insulins (BI) prescribed as an add‐on to or switch from glucagon‐like peptide‐1 receptor agonist (GLP‐1 RA) therapy. Materials and Methods: Retrospective, real‐world data from electronic medical records of 32 Italian diabetes clinics were used, after propensity score adjustment, to compare effectiveness after 6 months of treatment with second‐ versus first‐generation BI (2BI vs. 1BI) or glargine 300 U/ml versus degludec 100 U/ml (Gla‐300 vs. Deg‐100), when added to (ADD‐ON) or in substitution of (SWITCH) GLP‐1 RA. Only comparisons, including a minimum of 100 patients per group, were performed to ensure adequate robustness of the analyses. Results: In the ADD‐ON cohort (N = 700), greater benefits of 2BI versus 1BI were found in glycated haemoglobin {HbA1c; estimated mean difference: −0.32% [95% confidence interval (CI) −0.62; −0.02]; p =.04} and fasting blood glucose [FBG; −20.73 mg/dl (95% CI −35.62; −5.84); p =.007]. In the SWITCH cohort (N = 2097), greater benefits of 2BI versus 1BI were found in HbA1c [−0.22% (95% CI −0.42; −0.02); p =.03], FBG [−10.15 mg/dl (95% CI −19.04; −1.26); p =.03], and body weight [−0.67 kg (95% CI −1.30; −0.04); p =.04]. In the SWITCH cohort starting 2BI (N = 688), marked differences in favour of Gla‐300 versus Deg‐100 were documented in HbA1c [−0.89% (95% CI −1.26; −0.52); p <.001] and FBG [−17.89 mg/dl (95% CI −32.45; −3.33); p =.02]. Using propensity score matching as a sensitivity analysis, the benefit on HbA1c was confirmed [−0.55% (95% CI –1.02; −0.08); p =.02]. BI titration was suboptimal in all examined cohorts. Conclusions: 2BI are a valuable option to intensify GLP‐1 RA therapy. Switching to Gla‐300 versus Deg‐100 was associated with greater HbA1c improvement. [ABSTRACT FROM AUTHOR]

Abstract The dramatic increase in overweight and obesity among children and adolescents has become a major public health problem. Obesity in children and young adults is associated with an increased prevalence of cardiometabolic risk factors. Obesity during adolescence represents a strong predictor of obesity and higher mortality in adulthood. Due to the serious implications of obesity in adolescents, effective treatments are urgently needed. Lifestyle interventions represent the recommended therapy. Nevertheless, real world data show that the majority of adolescents do not achieve weight loss in the long term, and are reluctant to participate in lifestyle interventions. Pharmacological treatment is recommended if a formal lifestyle modification program fails to limit weight gain or to improve comorbidities. However, until 2020 the European Medicines Agency (EMA) had not approved any pharmacotherapeutic agents for obesity in pediatric patients. On April 2021, EMA has authorized the use of Liraglutide, a glucagon-like peptide (GLP)-1 analog, for the treatment of obesity in adolescents (12–17 years). The efficacy and safety of Liraglutide were demonstrated in a randomized, double-blind trial, enrolling 251 adolescents. After 56 weeks, a reduction in BMI of at least 5% was observed in 43.3% of participants in the liraglutide group vs. 18.7% in the placebo group, and a reduction in BMI of at least 10% was observed in 26.1 and 8.1%, respectively. Gastrointestinal events were the events most frequently reported with liraglutide. Bariatric surgery represents another effective treatment for adolescents with severe obesity, with sustained benefits on weight loss and cardiometabolic risk factors. However, long-term safety and effectiveness data in adolescents are still scarce. Risks of bariatric surgery include the need for additional abdominal surgical procedures and specific micronutrient deficiencies. Hopefully, new pharmacological treatments in addition to lifestyle interventions will offer more chances of success.

Abstract Background HbA1c variability has emerged as risk factor for cardiovascular diseases in diabetes. However, the impact of HbA1c variability on cardiovascular diseases in subjects within the recommended HbA1c target has been relatively unexplored. Methods Using data from a large database, we studied 101,533 people with type 2 diabetes without cardiovascular diseases. HbA1c variability was expressed as quartiles of the standard deviation of HbA1c during three years (exposure phase). The primary composite outcome included non-fatal myocardial infarction, non-fatal stroke, all-cause mortality and was assessed during five years following the first three years of exposure to HbA1c variability (longitudinal phase). An expanded composite outcome including non-fatal myocardial infarction, non-fatal stroke, coronary revascularization/reperfusion procedures, peripheral revascularization procedures, and all-cause mortality was also considered, as well as a series of specific cardiovascular complications. Cox models were adjusted for a large range of risk factors and results were expressed as adjusted hazard ratios. Results An association between HbA1c variability and all the outcomes considered was found. The correlation between HbA1c variability and cardiovascular complications development was confirmed in both the subgroups of subjects with a mean HbA1c ≤ 53 mmol/mol (recommended HbA1c target) or > 53 mmol/mol during the exposure phase. The risk related to HbA1c variability was higher in people with mean HbA1c ≤ 53 mmol/mol for the primary outcome (p for interaction 0.004), for the expanded secondary outcome (p for interaction 0.001) and for the stroke (p for interaction 0.001), even though HbA1c remained at the target during the follow-up. Conclusions These findings suggest that HbA1c variability may provide additional information for an optimized management of diabetes, particularly in people within the target of HbA1c.

To unfold the energy spectrum of two kilovoltage (kV) X-ray beams from transmission curves through a mathematical methodology based on Laplace transform and the generalized simulated annealing algorithm. Energy spectra of photon beams and transmission data were associated by means of a mathematical expression derived from the analytical solution of Laplace transform. Transmission data was calculated by relating the air kerma of the attenuated beams, passing through aluminium plates of different thickness, to that of the non-attenuated beam. Generalized simulated annealing function, developed in an early work, was employed to find the parameters of the expression and so determine the spectra. Validation of the methodology was done by the comparison of the half-value layers obtained from transmission curves and the spectra. The mean square percentage error between transmission data and fitting curve of each spectrum defined from the parameters found was lower than 1% indicating a good adjustment. The same error was observed when the first half-value layer (HVL) from the transmission curves and those of each reconstructed spectrum were compared. Calculation time of parameters was 5 sec for 80 kV and 14 sec for 120 kV. In no case, non-realistic solution of energy spectra was obtained. These results were better than an early work where least-squares were used. The reconstruction methodology based on generalized simulated annealing employed in this manuscript can efficiently derive the spectra of two X-ray beams with comparable accuracy to previous work. A limitation is that validation was not done by comparing data with the equipment’s spectra.

IntroductionObesity is a global pandemic and is cause of serious concern in all regions of the world. It is important to raise the attention of health care professionals in order to provide early treatment of patients with obesity. Obesity management, however, varies greatly amongst endocrinologists with respect to attitudes to diagnosis and treatment. Aim of this study was to identify practices and needs of Italian endocrinologists with respect to people with obesity.MethodsIn this study, all members of the Italian Association of Clinical Endocrinologists (AME) were invited to participate in a web-based survey concerning the management of obesity.ResultsThe response rate was 24.1% (542/2248). Nutritional and obesity problems were reported as major areas of interest by 29.4% of the participants. A large proportion of patients seeking an endocrine consultation for other reasons are affected by obesity, but one in five respondents addressed the issue in 25% or less of the cases, while one in three always dealt with the problem. Obesity was managed personally/within a dedicated team by 42.6% of participants, while the remainders referred the patient to a dietician/nutritionist or a 2nd level center for obesity therapy. Metformin was used in a median of 30% of the patients (Interquartile range: 10-50) and liraglutide in 10% of the cases (IQR 0-30), while orlistat (median 0%; IQR 0-10) and naltrexone/bupropion (median 0%; IQR 0-5) were seldom prescribed. Cost of therapy was considered as the major limitation to the use of anti-obesity drugs, affecting adherence to long-term treatment. According to 41.9% of respondents, psychological support should be offered to all patients with obesity. Finally, 56% of participants believe that the availability of new drugs will increase the number of patients candidate to drug therapy.DiscussionIn conclusion, it is of primary importance to raise the awareness of endocrinologists towards the problem of obesity and increase their confidence in managing this pathological condition.