In adult population, Growth Hormone Deficiency (GHD) is a complex clinical condition with heterogeneity of causes and duration. Growth Hormone (GH) replacement therapy has beneficial effects ...entailing a chronic and expensive use. Therefore, entity, appropriateness and standardization of GHD treatment need to be accurately analysed. In Italy, the epidemiological surveillance on somatropin therapy is entrusted to the National Register of Growth Hormone Therapy (Registro Nazionale degli Assuntori dell'Ormone della Crescita-RNAOC) by the Italian Regulation, in accordance of which the RNAOC-database is collecting the notifications of somatropin prescriptions.
Aim of this study is to analyse data on somatropin-treated adult population communicated to the RNAOC by the specialist centres of 15 Italian regions and 2 autonomous provinces.
From 2011 to 2019, the somatropin-treated adults were 970 with 4061 examinations (1.21 ± 0.33 visits/year). The diagnoses were: hypopituitarism (n = 579); hypophysectomy (n = 383); and congenital GHD (n = 3). Five subjects were addressed with diagnoses not included in the regulation. The starting posology of somatropin was 0.320 (± 0.212) mg/day, 0.292 (± 0.167) mg/day in male and 0.360 (± 0.258) in female patients, with 7 administrations/week in 70.31% of the prescriptions. The differences in posology by gender persisted at 10th year of the follow-up. Starting dosage was higher in patients diagnosed with adult GHD before the age of 30 (0.420 ± 0.225 mg/day), with a progressive decrease of the dosage during the follow-up.
This is the first report on adult GH treatment, describing numbers, diagnoses, and pharmaceutical prescriptions associated to somatropin therapy in a large cohort of Italian GHD-adults.
Recombinant human growth hormone (rhGH) is an approved and effective treatment for short children born small for gestational age (SGA). Prevalence of children eligible for treatment as SGA is ...reported to be 1:1800. The latest data from the National Registry of Growth Hormone therapy (RNAOC) showed that the number of children treated with SGA indication is still small (prevalence 0.37/100,000) and these children are significantly less reported than those treated for growth hormone deficiency (GHD), although GHD prevalence is 1:4000-1:10,000. This means that many short children born SGA are still not properly identified, and therefore not treated with rhGH, or misdiagnosed as GHD. This article provides some practical tools for the identification of children eligible for rhGH treatment.
Background
Epidemiological data obtained during the initial wave of the COVID-19 epidemic showed that persons dying with COVID-19 were typically older men with multiple chronic conditions. No studies ...have assessed if the characteristics of patients dying with COVID-19 have changed in the second phase of the epidemic, when the initial wave subsided. The aim of the present study was to compare characteristics of patients dying with COVID-19 in Italy in the first ‘peak’ phase of the epidemic and in its second phase.
Methods
Medical charts of patients with COVID-19 who died while in hospital in Italy were reviewed to extract information on pre-existing comorbidities, in-hospital complications, and disease trajectories. The course of the epidemic was classified in two 3-month periods: March–May 2020 and June–August 2020.
Findings
Overall, in the Italian population, 34,191 COVID-19 deaths occurred in March–May 2020 and 1,404 in June–August 2020. Patients dying in March–May were significantly younger (80.1 ± 10.6 vs. 82.8 ± 11.1 years,
p
< 0.001) and less frequently female (41.9% vs. 61.8%,
p
< 0.001) than those dying in June–August. The medical charts of 3533 patients who died with PCR-confirmed SARS-CoV-2 infection in March–May 2020 (10.3% of all deaths occurring in this period) and 203 patients who died in June–August 2020 (14.5% of all deaths occurring in this period) were analysed. Patients who died in March–May 2020, compared to those who died in June–August 2020, had
significantly lower rates
of multiple comorbidities (3 or more comorbidities: 61.8% vs 74.5%,
p
= 0.001) and superinfections (15.2% vs. 52.5%,
p
< 0.001). Treatment patterns also substantially differed in the two study periods, with patients dying in March–May 2020 being less likely to be treated with steroids (41.7% vs. 69.3%,
p
< 0.001) and more likely to receive antivirals (59.3% vs. 41.4%,
p
< 0.001). Survival time also largely differed, with patients dying in March–May 2020 showing a shorter time from symptoms onset to death (mean interval: 15.0 vs. 46.6 days,
p
< 0.001). The differences observed between the two periods remained significant in a multivariate analysis.
Interpretation
The clinical characteristics of patients dying with COVID-19 in Italy, their treatment and symptom-to-death survival time have significantly changed overtime. This is probably due to an improved organization and delivery of care and to a better knowledge of disease treatment.
Objective
This study aimed to assess the impact of obesity on nonrespiratory complications in patients dying with coronavirus disease (COVID‐19).
Methods
Medical charts of 3,694 of patients dying ...with COVID‐19 in Italy were reviewed to extract information on demographics, preexisting comorbidities, and in‐hospital complications leading to death. Multivariate logistic regressions were performed to assess the association of obesity with nonrespiratory complications. These analyses were adjusted for age, gender, and number of preexisting comorbidities.
Results
Obesity was present in 411/3,694 (11.1%) patients dying with COVID‐19. Obesity was significantly associated with increased probability of experiencing acute renal failure (adjusted odds ratio OR, 1.33; 95% CI: 1.04‐1.71) and shock (adjusted OR, 1.54; 95% CI: 1.19‐1.99). The associations of obesity with acute renal failure and shock were stronger in patients aged < 60 years (adjusted OR, 2.00; 95% CI: 1.09‐3.67 and OR, 2.37; 95% CI 1.29‐4.36) than in those aged 60 years or older (adjusted OR, 1.20; 95% CI: 0.90‐1.60 and OR, 1.22; 95% CI: 0.91‐1.65).
Conclusions
In patients dying with COVID‐19 in Italy, obesity is associated with an increased probability of nonrespiratory complications, particularly shock and acute renal failure. These associations seem stronger in younger than in older adults. Strategies should be put in place in patients with COVID‐19 with obesity to prevent these complications.
Among the unknowns posed by the coronavirus disease 2019 (COVID-19) outbreak, the role of biological sex to explain disease susceptibility and progression is still a matter of debate, with limited ...sex-disaggregated data available.
A retrospective analysis was performed to assess if sex differences exist in the clinical manifestations and transitions of care among hospitalized individuals dying with laboratory-confirmed SARS-CoV-2 infection in Italy (February 27-June 11, 2020). Clinical characteristics and the times from symptoms' onset to admission, nasopharyngeal swab, and death were compared between sexes. Adjusted multivariate analysis was performed to identify the clinical features associated with male sex.
Of the 32,938 COVID-19-related deaths that occurred in Italy, 3517 hospitalized and deceased individuals with COVID-19 (mean 78 ± 12 years, 33% women) were analyzed. At admission, men had a higher prevalence of ischemic heart disease (adj-OR = 1.76, 95% CI 1.39-2.23), chronic obstructive pulmonary disease (adj-OR = 1.7, 95% CI 1.29-2.27), and chronic kidney disease (adj-OR = 1.48, 95% CI 1.13-1.96), while women were older and more likely to have dementia (adj-OR = 0.73, 95% CI 0.55-0.95) and autoimmune diseases (adj-OR = 0.40, 95% CI 0.25-0.63), yet both sexes had a high level of multimorbidity. The times from symptoms' onset to admission and nasopharyngeal swab were slightly longer in men despite a typical acute respiratory illness with more frequent fever at the onset. Men received more often experimental therapy (adj-OR = 2.89, 95% CI 1.45-5.74) and experienced more likely acute kidney injury (adj-OR = 1.47, 95% CI 1.13-1.90).
Men and women dying with COVID-19 had different clinical manifestations and transitions of care. Identifying sex-specific features in individuals with COVID-19 and fatal outcome might inform preventive strategies.
Patients hospitalised for COVID-19 may present with or acquire bacterial or fungal infections that can affect the course of the disease. The aim of this study was to describe the microbiological ...characteristics of laboratory-confirmed infections in hospitalised patients with severe COVID-19.
We reviewed the hospital charts of a sample of patients deceased with COVID-19 from the Italian National COVID-19 Surveillance, who had laboratory-confirmed bacterial or fungal bloodstream infections (BSI) or lower respiratory tract infections (LRTI), evaluating the pathogens responsible for the infections and their antimicrobial susceptibility.
Among 157 patients with infections hospitalised from February 2020 to April 2021, 28 (17.8%) had co-infections (≤ 48 h from admission) and 138 (87.9%) had secondary infections (> 48 h). Most infections were bacterial; LRTI were more frequent than BSI. The most common co-infection was pneumococcal LRTI. In secondary infections, Enterococci were the most frequently recovered pathogens in BSI (21.7% of patients), followed by Enterobacterales, mainly K. pneumoniae, while LRTI were mostly associated with Gram-negative bacteria, firstly Enterobacterales (27.4% of patients, K. pneumoniae 15.3%), followed by A. baumannii (19.1%). Fungal infections, both BSI and LRTI, were mostly due to C. albicans. Antibiotic resistance rates were extremely high in Gram-negative bacteria, with almost all A. baumannii isolates resistant to carbapenems (95.5%), and K. pneumoniae and P. aeruginosa showing carbapenem resistance rates of 59.5% and 34.6%, respectively.
In hospitalised patients with severe COVID-19, secondary infections are considerably more common than co-infections, and are mostly due to Gram-negative bacterial pathogens showing a very high rate of antibiotic resistance.
there is concern about the increased risk for SARS-CoV-2 infection, COVID-19 severe outcomes and disparity of care among patients with a psychiatric disorder (PD). Based on the Italian COVID-19 death ...surveillance, which collects data from all the hospitals throughout the country, we aimed to describe clinical features and care pathway of patients dying with COVID-19 and a preceding diagnosis of a PD.
in this cross-sectional study, the characteristics of a representative sample of patients, who have died with COVID-19 in Italian hospitals between February 21st and August 3rd 2020, were drawn from medical charts, described and analysed by multinomial logistic regression according to the recorded psychiatric diagnosis: no PD, severe PD (SPD) (i.e. schizophrenia and other psychotic disorders, bipolar and related disorders), common mental disorder (CMD) (i.e. depression without psychotic features, anxiety disorders).
the 4020 COVID-19 deaths included in the study took place in 365 hospitals across Italy. Out of the 4020 deceased patients, 84 (2•1%) had a previous SPD, 177 (4.4%) a CMD. The mean age at death was 78.0 (95%CI 77.6–78.3) years among patients without a PD, 71.8 (95%CI 69.3–72.0) among those with an SPD, 79.5 (95%CI 78.0–81.1) in individuals with a CMD. 2253 (61.2%) patients without a PD, 62 (73.8%) with an SPD, and 136 (78.2%) with a CMD were diagnosed with three or more non-psychiatric comorbidities.
When we adjusted for clinically relevant variables, including hospital of death, we found that SPD patients died at a younger age than those without a PD (adjusted OR per 1 year increment 0.96; 95% CI 0.94–0.98). Women were significantly more represented among CMD patients compared to patients without previous psychiatric history (aOR 1.56; 95% CI 1.05–2.32). Hospital admission from long-term care facilities (LTCFs) was strongly associated with having an SPD (aOR 9.02; 95% CI 4.99–16.3) or a CMD (aOR 2.09; 95% CI 1.19–3.66). Comorbidity burden, fever, admission to intensive care and time from symptoms’ onset to nasopharyngeal swab did not result significantly associated with an SPD or with a CMD in comparison to those without any PD.
even where equal treatment is in place, the vulnerability of patients with a PD may reduce their chance of recovering from COVID-19. The promotion of personalised therapeutic projects aimed at including people with PD in the community rather than in non-psychiatric LTCFs should be prioritised.
Introduction
In hospitalized patients with COVID-19, bloodstream infections (BSI) are associated with high mortality and high antibiotic resistance rates. The aim of this study was to describe BSI ...etiology, antimicrobial resistance profile and risk factors in a sample of patients deceased with COVID-19 from the Italian National COVID-19 surveillance.
Methods
Hospital charts of patients who developed BSI during hospitalization were reviewed to describe the causative microorganisms and their antimicrobial susceptibility profiles. Risk factors were analyzed in univariate and multivariate analyses.
Results
The study included 73 patients (71.2% male, median age 70): 40 of them (54.8%) received antibiotics and 30 (41.1%) systemic steroids within 48 h after admission; 53 (72.6%) were admitted to intensive care unit. Early steroid use was associated with a significantly shorter interval between admission and BSI occurrence. Among 107 isolated microorganisms, the most frequent were
Enterococcus
spp.,
Candida
spp.,
Acinetobacter baumannii
, and
Klebsiella pneumoniae
. Median time from admission to BSI was shorter for
Staphylococcus aureus
compared to all other bacteria (8 vs. 24 days,
p
= 0.003), and longer for
Enterococcus
spp., compared to all other bacteria (26 vs. 18 days,
p
= 0.009). Susceptibility tests showed a high rate of resistance, with 37.6% of the bacterial isolates resistant to key antibiotics. Resistance was associated with geographical area adjusted odds ratio (AOR) for Central/South Italy compared to North Italy: 6.775,
p
= 0.002, and with early use of systemic steroids (AOR 6.971,
p
= 0.018).
Conclusions
In patients deceased with COVID-19, a large proportion of BSI are caused by antibiotic-resistant bacteria. Early steroid use may facilitate this occurrence.
Maize (
Zea mays L., cv. Samodek) callus cultures were exposed for long period (22 months) to lead (0.5 mM lead chloride) and lead content, oxidative damage and antioxidative response were evaluated ...at different steps. Inductively coupled plasma (ICP) emission spectroscopy analysis showed that lead entered the cells and it accumulated, but its internal concentration was maintained 10-fold less than the external one. Increase of both polyamine and lipid peroxide content indicated that cells underwent a stress condition due to an oxidative attack, counteracted by an increase of antioxidative defence enzyme activities, ascorbate peroxidase (APX, EC 1.11.1.11) and glutathione reductase (GR, EC 1.6.4.2). After 10 months, from the start of the lead treatment, a stock of calli was transferred for 6 months in a lead-deprived medium and then re-exposed to lead for a further 6 months. Analysis indicated that lead-deprived calli maintained high levels of APX and GR activities, suggesting that, over the experimental time–course, cells with high APX and GR activity were selected and allowed to enrich the cultures. These cultures, after a new lead treatment, showed a lower oxidative damage compared to continuously lead-treated calli.
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