The economic burden of pediatric growth hormone deficiency in Italy: a cost of illness study.

PURPOSE: Growth hormone deficiency (GHD) is a rare condition with a worldwide prevalence of 1 patient in 4000 to 10,000 live births, placing a significant economic burden on healthcare systems. The aim of this study is to generate evidence on the economic burden of children and adolescents with GHD treated with rhGH and their parents in Italy. METHODS: A cost of illness analysis, adopting the prevalence approach, has been developed, producing evidence on the total annual cost sustained by the Italian National Health System (NHS) and by the society. The study is based on original data collected from a survey conducted among Italian children and adolescents with GHD and their parents. RESULTS: 143 children/adolescents with GHD and their parents participated to the survey, conducted from May to October 2021. Patients had a mean age of 12.2 years (SD: 3.1) and were mostly males (68.5%). The average direct healthcare cost sustained by the NHS was € 8,497.2 per patient/year; adding the out-of-pocket expenses (co-payments and expenses for private healthcare service), the total expense was € 8,568.6. The indirect costs, assessed with the human capital approach, were € 847.9 per patient/year. The total of direct and indirect cost is € 9,345.1 from the NHS perspective, and € 9,416.5 from a social perspective. The total cost incurred by the Italian NHS for children with GHD (range: 5,708-8,354) was estimated in € 48.5-71.0 million, corresponding to 0.04-0.06% of the total Italian public health expense in the year 2020. CONCLUSIONS: The total annual cost for GHD children is close to € 10,000, and is mainly due to the cost of rhGH treatment. This cost is almost entirely sustained by the NHS, with negligible out-of-pocket expenses. The economic burden on the Italian NHS for the health care of established GHD children is fourfold higher than the prevalence of the disease in the overall Italian population.

Quality of life in children and adolescents with growth hormone deficiency and their caregivers: an Italian survey.

PURPOSE: The aim of this study was to produce evidence on quality of life (QoL) among Italian growth hormone deficiency (GHD) children and adolescents treated with growth hormone (GH) and their parents. METHODS: A survey was conducted among Italian children and adolescents aged 4-18 with a confirmed diagnosis of GHD and treated with GH therapy and their parents. The European Quality of Life 5 Dimensions 3 Level Version (EQ-5D-3L) and the Quality of Life in Short Stature Youth (QoLISSY) questionnaires were administered between May and October 2021 through the Computer-Assisted Personal Interview (CAPI) method. Results were compared with national and international reference values. RESULTS: The survey included 142 GHD children/adolescents and their parents. The mean EQ-5D-3L score was 0.95 [standard deviation (SD) 0.09], while the mean visual analogue scale (VAS) score was 86.2 (SD 14.2); the scores are similar to those of a reference Italian population aged 18-24 of healthy subjects. As for the QoLISSY child-version, compared to the international reference values for GHD/ idiopathic short stature (ISS) patients, we found a significantly higher score for the physical domain, and lower scores for coping and treatment; compared to the specific reference values for GHD patients, our mean scores were significantly lower for all domains except the physical one. As for the parents, we found a significantly higher score for the physical domain, and a lower score for treatment; compared to reference values GHD-specific, we found lower score in the social, emotional, treatment, parental effects, and total score domains. CONCLUSIONS: Our results suggest that the generic health-related quality of life (HRQoL) in treated GHD patients is high, comparable to that of healthy people. The QoL elicited by a disease specific questionnaire is also good, and comparable with that of international reference values of GHD/ISS patients.

Host factors and history of SARS-CoV-2 infection impact the reactogenicity of BNT162b2 mRNA vaccine: results from a cross-sectional survey on 7,014 workers in healthcare.

OBJECTIVE: This study aimed to improve the post-marketing surveillance on mRNA anti-SARS-CoV-2 vaccines, characterizing the adverse events (AEs) after the first dose of mRNA BNT162b vaccine. The associations between the AEs and individuals' characteristics were explored. PATIENTS AND METHODS: All adult healthcare workers at Niguarda Hospital (Milan, Italy) who were referred for the first dose of vaccine were offered to participate in a cross-sectional survey during the second-dose administration, between 18 January and 7 February 2021. All participants completed a questionnaire about age, gender, weight, height, medical history, concurrent therapies, employment status, previous diagnosis/testing for SARS-CoV-2 infection, and a list of 24 AEs (solicited AEs). The development of at least one solicited AEs was the main outcome. AEs were stratified by the presence of injection-site symptoms, systemic symptoms or both, and the differences between strata were assessed as a secondary outcome. Biometric data and reports of a previous diagnosis of SARS-CoV-2 infection were also explored, as predictors of the main outcome. RESULTS: 7,014 healthcare workers were included. An incidence of 3 per 10.000 persons for serious AEs following the first administration of the mRNA BNT162b vaccine was found. An association between the development of non-serious AEs with young age, female gender, low body mass index, and previous history of SARS-CoV-2 was described. CONCLUSIONS: This real-life study supported data on the safety profile of the BNT162b2 mRNA vaccine. Our findings on the associations between the development of non-serious AEs with some individual characteristics may help physicians and patients make educated and informed medical decisions towards anti-COVID-19 vaccination.

Worldwide prevalence of malocclusion in the different stages of dentition: A systematic review and meta-analysis.

AIM: The aim of this review is to quantify the prevalence and type of malocclusion among children and adolescents during the different stages of dentition worldwide. MATERIALS AND METHODS: Recent studies (from 2009 to 2019), published in Medline, Web of Science and Embase and orthodontic text-books have been comprehensively reviewed herein. The methodological quality of the included studies was assessed using STROBE criteria. RESULTS: After screening 450 records and analysing 284 relevant full-text publications, 77 studies were included in this review. A good degree of evidence was obtained due to the medium-high methodological quality level of included studies. The worldwide prevalence of malocclusion was 56% (95% CI: 11-99), without differences in gender. The highest prevalence was in Africa (81%) and Europe (72%), followed by America (53%) and Asia (48%). The malocclusion prevalence score did not change from primary to permanent dentition with a common score of 54%. Malocclusion traits such as Angle's classes, overjet, overbite, and asymmetrical midline shift essentially did not change their prevalence during different dentitions. Conversely, traits such as cross-bite and diastema reduced their prevalence during permanent dentition, while scissor-bite and dental crowding increased their scores. CONCLUSION: The worldwide high prevalence of malocclusion and its early onset during childhood should induce policymakers as well as paediatric physicians and dentists to devise policies and adopt clinical strategies for preventing malocclusion since younger children's ages.

Sub-ablative laser irradiation to prevent acid demineralisation of dental enamel. A systematic review of literature reporting in vitro studies.

AIM: Caries lesions begin with enamel acid demineralisation mediated by microorganisms. Lasers with sub-ablative energy might act as a prophylactic intervention to reinforce enamel against lesions caused by acid. MATERIALS AND METHODS: A systematic review of the literature was performed evaluating only in vitro studies published from 2010 to 2018. The research was performed using the following databases: Medline, Embase and the Web Of Science. A further search was performed consulting the list of references of the included studies as well as book chapters which dealt with this topic. RESULTS: A total of 347 records were retrieved and, after their evaluation, 36 studies were included. CO2 lasers were the most described and effective device in preventing acid demineralisation. This type of laser was unique in improving the already positive results obtained with fluoride-based interventions. Er,Cr:YSGG (with fluencies > 8.5J/cm2), diode and argon lasers also improved enamel acid resistance (p-values ranging from 0.05 to 0.001) producing similar effects with fluoride-based interventions. Regarding the sealant retention outcome, the Er:YAG laser was able to perform an enamel etching which was as effective as the traditional acid etching with the advantage of being easier and usually well accepted by low-compliant patients (i.e. younger children). Nd:YAG presented the worst results. The most common structural changes after the laser irradiation were water and carbonate reduction in the enamel combined with a phosphate and calcium enamel content increase. Moreover, the calcium/phosphate ratio was found to reach the 1.67 ideal ratio. CONCLUSION: The in vitro studies that examined the prophylactic use of lasers for increasing enamel acid resistance presented interesting results that are enough to support a further in vivo experiment. This would entail the use of a clinical laser as an alternative or in combination with fluoride-based interventions.

[Occupational diseases caused by artificial optical radiation (AOR)]. / Le malattie professionali da radiazioni ottiche artificiali (ROA).

BACKGROUND: Italian national legislation guarantees safety and health for workers exposed to artificial optical radiations (AOR) by Legislative Decree 81/2008. OBJECTIVES AND METHODS: Effects and damages to health resulting from AOR exposure were analyzed from literature data. RESULTS: Ultraviolet radiations (UV), particularly those in the wavelength range between 220 and 310 nm, causes chronic conjunctivitis and kerato-conjunctivitis. Skin cancer caused by UV exposure included basal cell carcinoma, squamous cell carcinoma and melanoma. As regards Infrared Radiations (portion of the spectrum between 780 nm and 1 mm), the biological effect is essentially of thermal nature. Exposure to blue light (portion ofthe spectrum of visible light radiation in a wavelength range between 380 and 550 nm) causes exclusively retinal damage and is considered to be responsible for the development of situations of age-related macular degeneration (AMD). Even if experimental data are available, at the present time there is still no epidemiological evidence of retinal damage caused by blue light. CONCLUSIONS: The forensic criteria for investigating the causality link between occupational exposure to AOR and damage, and the methodology necessary for the assessment process, are reported. Two lists of occupational diseases which were included in the Italian Ministerial Decrees, issued respectively on April 2008 and 11 December 2009, are also considered. Lastly, on the basis of the current existing guidelines and scientific evidence, the authors propose occupational health surveillance protocols for workers exposed to AOR risk.

Involvement of X-box binding protein 1 and reactive oxygen species pathways in the pathogenesis of tumour necrosis factor receptor-associated periodic syndrome.

OBJECTIVES: To investigate convergence of endoplasmic reticulum stress pathways and enhanced reactive oxygen species (ROS) production, due to intracellular retention of mutant tumour necrosis factor receptor 1 (TNFR1), as a disease mechanism in TNFR-associated periodic syndrome (TRAPS). METHODS: Peripheral blood mononuclear cells from patients with TRAPS (n=16) and healthy controls (HC) (n=22) were studied alongside HEK293T cells expressing wild type-TNFR1 or TRAPS-associated mutations. Unfolded protein response (UPR)-associated proteins (protein kinase-like endoplasmic reticulum kinase, PERK), phosphorylated-PERK (p-PERK), phosphorylated inositol-requiring enzyme 1α (p-IRE1α) and spliced X-box binding protein 1 (sXBP1)) were measured by flow cytometry. XBP1 splicing and UPR-associated transcript expression were assessed by reverse transcription PCR/quantitative real-time PCR. ROS levels were measured using CM-H(2)DCFDA and MitoSOX Red in patients' monocytes or HEK293T cells by flow cytometry. RESULTS: Mutant TNFR1-expressing HEK293T cells had increased TNFR1 expression associated with intracellular aggregation. TRAPS patients had increased sXBP1 transcripts (p<0.01) compared with HC. Raised p-PERK protein was seen, indicative of an UPR, but other UPR-associated transcripts were normal. Increased ROS levels were observed in TRAPS monocytes compared with HCs (p<0.02); these increased further upon IL-6 stimulation (p<0.01). Lipopolysaccharide-stimulated peripheral blood mononuclear cells of patients with TRAPS, but not HCs, demonstrated increased sXBP1 levels (p<0.01), which were reduced by antioxidant treatment (p<0.05). CONCLUSIONS: Patients with TRAPS have evidence of increased sXBP1 and PERK expression but without other signs of classical UPR, and also with high ROS generation that may contribute to the pro-inflammatory state associated with TRAPS. The authors propose a non-traditional XBP1 pathway with enhanced sXBP1 as a novel disease-contributing mechanism in TRAPS.

The contribution of Enrico C. Vigliani (1907-1992) to the international development of occupational medicine and industrial hygiene.

BACKGROUND: One of the last century's greatest personalities in Occupational Medicine was Enrico Carlo Vigliani (1907-1992), director of the "Clinica del Lavoro" in Milan (1942-1977), editor-in-chief of "La Medicina del Lavoro" (1942-1991), Secretary-Treasurer and then President of the "Permanent Commission and International Association on Occupational Health" (1957-1981), the original nucleus of the ICOH. OBJECTIVES: The 20th anniversary of his death provides us with the opportunity to discuss the role of this brilliant scholar in the international development of Occupational Medicine and Industrial Hygiene. METHODS: A comprehensive analysis of Vigliani's scientific works was conducted. In addition, his close collaborators and pupils were interviewed. RESULTS: In the 1930s, as a young doctor, Vigliani, first in the world, demonstrated the effect of lead on porphyrin metabolism. Afterwards he conducted pioneering studies on occupational oncology (benzene-induced leukaemia, bladder cancer due to aromatic amines, asbestos-related tumours), pathogenesis of silicosis, encephalopathy in carbon disulfide poisoning, byssinosis and metal fume fever, so influencing international research and the implementation of preventive measures against these conditions. Vigliani's scientific authority was widely recognized internationally, as confirmed by his role in ICOH. During his period of active service, the Commission developed from an academic institution to a more open association, substantially increasing its membership. Furthermore, he contributed to establishing subcommittees devoted to specific topics (now called "scientific committees"), one of the strengths of the present Commission. CONCLUSIONS: Vigliani's contribution to the development of Occupational Health may be considered as an expression of his genial eclecticism which ranged from clinical medicine to the environment.

[Evaluation of residual osteomuscular function using computerised movement analysis for building sector workers: specificity and technical problem]. / La valutazione della funzionalità osteomuscolare residua tramite l'analisi computerizzata del movimento nei lavoratori del comparto edile: specificità e problematicità.

Occupational Health Doctors active in building sector firms frequently have to evaluate residual workers' osteomuscular function in patients coming back to work after an accident happened during work time or free time. Definition of their specific individual work suitability is usually carried out utilizing semeiotic tests in which subjective evaluation of every single Medical Doctor is real important in definition of final results and this fact can cause legal controversies. In our research we describe the application of computerised movement analysis on 10 workers of building sector. In every patient examined this technical method has been able to study objectively the tridimensional ranges of motion of most important osteomuscular districts. The possibility to have an objective evaluation of residual osteomuscular function has a relevant importance both in definition of workers' work suitability at the moment in which they start again their activities and in possible future legal conflicts.

[Use of barrier creams in occupational health: utility, limits and actual diffusion in clinical practice]. / L'utilizzo delle creme barriera in Medicina dei Lavoro: finalità, limiti ed attuale impiego nella pratica clinica.

Use of barrier creams among workers exposed to chemical risk has changed during last years and actually seems not to be very largely widespread even if there are not many up to date data about it. We report a research carried out evaluating effective presence in pharmacological market of barrier creams, their chemical characteristics, their composition, their prize. We analyzed the prescription of barrier creams made by 45 Occupational Doctors active in 2730 firms, their knowledge of chemical and pharmacological aspects which can make the difference among creams. We also considered motivations of their frequent or rare barrier cream prescription.

[A survey on dental offices: risk assessment and practicable preventive and protective measures]. / Indagine su un campione di studi odontoiatrici: valutazione dei rischi e misure preventive e protettive attuabili.

The survey was aimed at developing a method and providing valuable tools to be used for risk assessment in dental practices and for the implementation of preventive and protective measures. For these purposes general (inspection card for the definition of risk level for health and safety) and specific tools (check-lists) were used. In each dental office chemical and physical hazards (noise and hand-arm vibration) were assessed. Adequate levels of security were achieved, even if workers' training was evidenced as a critical element. In the 90% of cases, rooms for specific use were available and suitable according the law. The risk of work-related stress was acceptable in almost all the analyzed dental offices. Chemical and specific physical hazards appeared to be below the action level. Biological risk doesn't seem to be a critical element, even though its control could be further improved.

[Hepatitis B vaccination coverage and booster dose: results from a survey on healthcare students]. / Copertura vaccinale anti-epatite B e dose di rinforzo: risultati di uno studio su una popolazione universitaria.

This study assessed the immunisation status against hepatitis B in healthcare students and residents, before their hospital internship, as suggested by the "National Immunization Prevention Plan 2012-2014". The concentration of antibodies against hepatitis B was measured in 2,491 subjects (70.90% women), born between 1980 and 1993 and visited between January 1st 2000 and July 15th 2012. Personal and serologic data were collected for each subjects. Individuals with antibody less than 10 mIU/mL (327, 13.3%) were given a booster dose and re-tested 2 months later. The multivariate logistic regression evidenced that immunization is influenced by the gender, the age at first vaccination, the time elapsed between first vaccination and antibody measurement. This study confirms the importance of measuring the concentration of antibodies against hepatitis B among healthcare students, even if they have previously been vaccinated, according to the "National Immunization Prevention Plan 2012-2014".

[Use of computerized stabylometric footboard in evaluation of work suitability at height work in building firms]. / L'utilizzo della pedana stabilometrica computerizzata come ausilio nella definizione della idoneità al lavoro in altezza nel comparto edile.

A relevant part of deadly work accidents and of severe work accidents reported in national specific statistics coming from INAIL is until today caused by workers' falls during their at height work activities. Medical evaluation of eventual workers' hyper susceptibility to fall caused by balance alterations, if included in medical surveillance, is frequently carried out by medical doctors using different subjective tests included in different clinical protocols. Use of a computerized stabylometric footboard on the contrary allows to obtain objective and reproducible data concerning vestibular function which, associated with traditional clinical medical evaluation, seem to better detect eventual presence of balance disturbances, especially those non clinically perceivable by workers and therefore more dangerous. We report results evidenced in a research carried out in a group of 185 workers engaged in building firms and having work tasks including phases of at height work.

[Medical surveillance in university: organizational difficulties, legal problems, scientific e technical specificities. Experience of University of Milan Bicocca]. / La sorveglianza sanitaria nelle università: problemi organizzativi, medico legali e tecnico scientifici. La esperienza della Università di Milano Bicocca.

Our research describes activities of Occupational Health carried out during last year in University of Milan Bicocca by Occupational Doctors. We describe results of medical surveillance in 1153 employees or students exposed to occupational risks for health and safety. We report results obtained, technical difficulties, organizational problems, and preventive actions decided to improve functionality of our activity. Students seem to be less protected and consequently seem to have higher professional safety and health risks.

[Medical surveillance of Italian Red Cross Volunteers: actual limits of law, technical and scientific problems. The experience of Red Cross Provincial Committee of Monza and Brianza]. / La sorveglianza sanitaria dei Volontari della Croce Rossa Italiana: limiti normativi e problematiche tecnico scientifiche. La esperienza del Comitato Provinciale CRI di Monza e Brianza.

Our research describes a medical surveillance, not included in usual Occupational Health activities, carried out in last year among Red Cross Volunteers active in Monza e Brianza Provincial Committee. This medical surveillance has been managed according to internal rules of Red Cross and national specific Laws. We report data concerning medical examination of 1285 volunteers, their consequences on their voluntary activities, problems arisen during and after medical controls. Starting from results of our medical controls, we evaluated legal and organizational possibilities of evolution of medical surveillance of Red Cross Volunteers specifically and more generally of Civil Protection Volunteers, considering specific new law recently promulgated which seem partially not homogeneous with 81/08 Decree.

[Work-related stress risk assessment in a home care agency]. / La valutazione del rischio stress lavoro-correlato in una cooperativa di assistenza domiciliare.

The workload, the quality of professional relationships and emotional involvement have a significant impact on distress and burnout in health care-workers; this impact has an hight variability among the different environments and different care facilities (hospital, erderly nursing homes, home care). The risk assessment of work-related stress performed in 2010 in a homecare agency highlighted organizational problems related to the content/context of work and risk factors for health and safety. High turn-over is evidenced as critical among the "sentinel events". The level of job-strain was moderate, even if some critical issues were evidenced especially in the group of physiotherapists; nurses were configured as a homogeneous group with a low level of job-strain. In informative meetings the workers identified the discomfort related to the time for transferring patients from their homes in a high-traffic metropolitan area was identified as the most critical aspect.

[Urinary evaluations of drug consumption among workers having high risk of accident: technical difficulties, limits and possibilities of increasing efficacy of the law]. / Le valutazioni bioumorali del consumo di stupefacenti nei lavoratori a rischio di infortunio per terzi: criticità tecniche, limiti e possibilità di incremento della efficacia della norma.

Urinary evaluations of drug consumption among workers having high risk of accident became compulsory in Italian legislation few years ago. We report results of 322.110 single urinary drug detections carried out between 2008 and 2011 on 35.789 subjects. We verified technical difficulties arisen during laboratory detections and organizational difficulties evidenced by Occupational Doctors during collections of samples. We screened 701 positive samples (1.96%), mostly to Cannabinoids and Cocaine, verified using first and second level screening according to national law. Many patients referred regular or irregular use of medicines active on Central Nervous System frequently ignoring their collateral effects. After the evidence of a positive result, during a second medical visit, many workers referred assumption of "natural diet supplements" acquired not in traditional commercial distributors. In two cases we have had the possibility of analyzing these supplements which have shown the presence of law concentrations of drugs in their compositions.

[The movement computerized analysis as instrumental support for occupational doctors in evaluation of upper limb pathologies in engineering workers]. / L'analisi computerizzata del movimento come strumento di supporto al Medico del Lavoro nella valutazione dei disturbi muscolo-scheletrici degli arti superiori nel comparto metalmecanico.

The movement computerized analysis of upper limb is a valid support in the definition of residual functional capability and of specific work suitability in complex cases. This methodology of evaluation is able to correctly and objectively define the tridimensional ranges of motion of every patient's upper limb. This fact can be particularly useful for workers coming back to work after a work-related or a not work-related accident of for handicapped workers at the beginning of a new work activity. We report a research carried out using computerized analysis of motion of upper limbs in 20 engineering workers.

[Sentinel events for work-related stress in hospital and their monitoring in the decade 2001-2010]. / Eventi sentinella stress lavoro-correlati in ambito ospedaliero e lore monitoraggio nel decennio 2001-2010.

This survey was aimed at showing the relationship between some working organizational indicators--work-related stress "sentinel events" such as sick leaves and work accident--and some sociodemographic (gender, age) and organizational (homogeneous tasks, departmental areas) parameters. In the decade 2001-2010 a progressive decrease of the absenteeism and work accident rates was evidenced. The absenteeism rate was inversely related to job-qualification and it was higher among female workers. The highest requests of medical visits by auxiliary personnel showed a lower adaptation to job content, looked upon as low-rewarding in this homogeneous task.