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.

Dental implant procedures in immunosuppressed organ transplant patients: a systematic review.

During the last decades, the number of immunosuppressed organ transplant patients has increased consistently. Nevertheless, immunosuppression has been discussed as a contraindication for dental implant procedures for many years. Hence, the purpose of this systematic review was to assess the survival rate and outcomes of dental implants after solid organ transplantation. An electronic and manual literature search was conducted up to March 2021. Publications describing dental implants placed in patients after organ transplantation were included without any limitations regarding study design or date of publication. Ten articles met the inclusion criteria, leading to a sample of 93 patients with 249 implants. Implant survival rates were 100% over a mean follow-up of 60 months. In every case, implant surgery was performed under antibiotic coverage. No major medication-related complications were reported. Despite the limited amount of evidence in the literature, implant procedures seem to be a safe treatment option in immunosuppressed organ transplant patients. The observance of appropriate treatment protocols including a strict maintenance programme seems to be crucial for the long-term success of such treatments. However, stringent data regarding various influencing factors such as the prevalence of peri-implantitis are still missing.

Emerging new avian reovirus variants from cases of enteric disorders and arthritis/tenosynovitis in Brazilian poultry flocks.

1. The objective of this study was to characterise circulating Brazilian avian reovirus (ARV) strains by genetic analysis of the σC protein encoded by segment 1 of the viral genome and compare these with those of viral strains used for immunising commercial poultry.2. The analysis detected the presence of ARV genomes by quantitative reverse transcriptase PCR (RT-qPCR) in the enteric samples and the joint tissues (JT) of birds with signs of viral arthritis/tenosynovitis. Nucleotide sequencing used 16 strains (three commercial vaccines, 10 from enteric tissues and three from JT). The results indicated high variability in the amino acid sequences of 13 wild strains, showing between 40% and 75% similarity compared with the vaccine strains (S1133 and 2177).3. The sequences were grouped into three well-defined clusters in a phylogenetic tree, two of these clusters together with previous Brazilian σC ARV sequences, and one cluster (VII) that was novel for Brazilian strains. Antigenic analysis showed that there were amino acids within putative epitopes located on the surface of the receptor-binding region of the σC protein with a high degree of variability.4. The study confirmed the presence of ARV genetic variants circulating in commercial birds in Brazil, and according to the antigenic prediction, the possibility of antigenic variants appears to be high.

Intraligamentary anaesthesia as a possible anaesthetic option in oral implantology: a retrospective analysis.

This investigation was conducted to analyse the usefulness of intraligamentary anaesthesia (ILA) as an alternative anaesthetic procedure in oral implantology. Forty consecutive patients with single-tooth gaps in the posterior mandible were included in the analysis. Implant insertion was performed after ILA of the gap-delimiting teeth (two injections distal to the mesial tooth, two injections mesial to the distal tooth). Implant surgery was performed successfully under ILA of the gap-delimiting teeth in 39 cases. Injection pain correlated significantly with lower periodontal probing depths (<3mm) of the delimiting teeth (P=0.003). The total amount of anaesthetic solution and the pain during surgery were significantly higher if a root canal-treated tooth was present in the area of surgery (P=0.010 and P=0.020, respectively). Overall, the mean pain score during treatment was low at 0.76±0.51 on a numerical rating scale from 0 to 10. At the control visit, no major complication was encountered. All implants were successfully restored with single crowns after a healing period of 2 months. Taking into consideration the limitations of the study, ILA seems to fulfil all conditions to be defined as an alternative, minimally invasive anaesthetic technique for the insertion of single-gap implants.

Usos del láser terapéutico en Odontopediatría: Revisión de la literatura. Reporte de casos / Uses of Therapeutic Laser in Pediatric Dentistry: Review of the Literature. Case Reports

RESUMEN El término "LÁSER" es un acrónimo de "Light Amplification by the Stimulated Emission of Radiation" (en español "Amplificación de Luz por Emisión Estimulada de Radiación"). La utilización de la tecnología láser en Odontología ha tenido una constante evolución y desarrollo en los últimos 30 años. Se deben distinguir dos grandes grupos de láseres: De alta potencia o quirúrgicos y de baja potencia o terapéuticos. El más empleado en odontología pediátrica es el terapéutico o LLLT (o "blando"). El láser terapéutico está indicado para diversas anomalías tales como la hipersensibilidad, gingivitis, herpes, parestesias, neuralgias del trigémino, trismus, disfunción ATM, implantes, activación de químicos de blanqueamiento dental, entre otros. Este artículo pretende realizar una actualización de las aplicaciones del láser de baja potencia en el ámbito de la Odontología Pediátrica, así como la presentación de 4 casos clínicos representativos.

ABSTRACT The term "LASER" is an acronym for "Light Amplification by the Stimulated Emission of Radiation" (in Spanish "Amplificación de Luz por Emisión Estimulada de Radiación"). The use of laser technology in dentistry has had a constant evolution and development in the last 30 years. Two large groups of lasers should be distinguished: high-power or surgical and low-power or therapeutic. The most used in pediatric dentistry is the therapeutic or LLLT (or "soft"). The therapeutic laser is indicated for various anomalies such as hypersensitivity, gingivitis, herpes, paresthesias, trigeminal neuralgias, trismus, TMJ dysfunction, implants, activation of teeth whitening chemicals, among others. This article intends to perform an update of the applications of low power laser in the field of Pediatric Dentistry, as well as the presentation of 4 representative clinical cases.

Long-term influence of mandibular advancement on the volume of the posterior airway in skeletal Class II-patients: a retrospective analysis.

In the past, maxillomandibular advancement has resulted in considerable improvement in the volume of the posterior airway space. The objective of the present study was to find out how mandibular advancement without maxillary involvement would affect the posterior airway space in patients with mandibular retrognathism. Cone-beam computed tomographic (CT) scans were done for 20 patients before, and six months after, mandibular advancement. Cephalometric analysis at both time points included 2-dimensional and 3-dimensional assessment of the upper airway. Eight men and 12 women presented a preoperative mean (SD) Wits value of 7.4 (1.54) mm, with an airway area of 7.11 (1.88) cm2 and a volume of 14.92 (4.46) cm3. Six months postoperatively they showed a Wits value of 2.7 (0.41) mm, an airway area of 11.33 (3.49) cm2, and a volume of 25.7 (6.10) cm3. There was a mean (range) enlargement of 59 (22-82) % of the area and 73 (29-108) % of the volume. A preoperative Wits value of 8mm or more correlated significantly with a larger increase of the posterior airway space (p=0.002). At the same time, an improvement in the Wits value of 4.5mm or more correlated significantly with an increase in volume (p=0.016). The effect of mandibular advancement on the posterior airway space was significant, and the volumetric effect seems to be even more relevant than the two-dimensional changes.

The impact of sexual behavior on oral HPV infections in young unvaccinated adults.

OBJECTIVE: Different authors hypothesized an important impact of sexual behavior on the prevalence of oral human papillomavirus (HPV) infections. In order to investigate this relationship more in detail and in contrast to most other studies, the present work focused on the population group with the highest risk for sexually transmitted infections: young and sexual active adults. MATERIALS AND METHODS: Three hundred and ten men and women aged 18-30 years could be recruited. After the completion of a risk-factor survey, brush smear samples for oral HPV detection were taken in every participant. RESULTS: In 18.1 %, oral HPV could be detected. Overall, smoking (p = 0.0074) and a high number of different sexual partners (vaginal: p = 0.0001; oral: p < 0.0001) were significantly correlated with a positive HPV testing. In case of high risk HPV infections, besides tobacco and sexual behavior, alcohol consumption showed a significant association with a positive testing (p = 0.0212). CONCLUSIONS: Overall, the prevalence of oral HPV seems to be higher in young, sexual active adults compared to other population groups. Tobacco and alcohol may facilitate an oral HPV infection. Sexual behavior, especially oral sex practices, seems to play a crucial role in the transmission of oral HPV. CLINICAL RELEVANCE: The presented data, especially the association of oral high risk HPV positivity and promiscuity, may lead to improvements in the existing oral HPV prevention strategies like a HPV vaccination for both genders.

Ridge augmentation in an organ transplant patient.

With the continuing progress in medicine, the number of successful organ transplantations has continued to increase, a fact that also concerns dentists and implantologists. Implantology after organ transplantation remains controversial due to the patient's immunocompromised situation and the corresponding risk of infection. Only a few studies on this topic have been reported, with all of them showing the dental implant success rates in transplant patients to be similar to those in healthy subjects. However, immunosuppression has been identified as a contraindication to bone augmentation. Consequently, there is still a lack of knowledge regarding pre-implantology bone grafting procedures. The following case report describes the use of ridge augmentation and extended bilateral sinus lift procedures in a liver transplant patient. The patient was treated with an implant-supported fixed prosthesis in the upper jaw and was followed up for a total of 28 months after implant insertion. According to the findings presented, pre-implantology augmentation procedures may be performed successfully in immunosuppressed organ transplant patients. Stable peri-implant conditions were shown over a period of more than 2 years. Nevertheless, further investigations are needed to define a safe treatment protocol for these high-risk patients.

Ultralow-dose computed tomography imaging for surgery of midfacial and orbital fractures using ASIR and MBIR.

The influence of dose reductions on diagnostic quality using a series of high-resolution ultralow-dose computed tomography (CT) scans for computer-assisted planning and surgery including the most recent iterative reconstruction algorithms was evaluated and compared with the fracture detectability of a standard cranial emergency protocol. A human cadaver head including the mandible was artificially prepared with midfacial and orbital fractures and scanned using a 64-multislice CT scanner. The CT dose index volume (CTDIvol) and effective doses were calculated using application software. Noise was evaluated as the standard deviation in Hounsfield units within an identical region of interest in the posterior fossa. Diagnostic quality was assessed by consensus reading of a craniomaxillofacial surgeon and radiologist. Compared with the emergency protocol at CTDIvol 35.3 mGy and effective dose 3.6 mSv, low-dose protocols down to CTDIvol 1.0 mGy and 0.1 mSv (97% dose reduction) may be sufficient for the diagnosis of dislocated craniofacial fractures. Non-dislocated fractures may be detected at CTDIvol 2.6 mGy and 0.3 mSv (93% dose reduction). Adaptive statistical iterative reconstruction (ASIR) 50 and 100 reduced average noise by 30% and 56%, and model-based iterative reconstruction (MBIR) by 93%. However, the detection rate of fractures could not be improved due to smoothing effects.

Odontogenic deep neck space infection as life-threatening condition in pregnancy.

Odontogenic deep neck space infections represent a severe disease with possible life-threatening complications. Despite knowledge of these infectious diseases, treatment remains a challenge for every maxillofacial surgeon. Therapy of severe neck infections is even more crucial during pregnancy because of the possible life-threatening situation for both the mother and the foetus. The possible compromise of oral health during pregnancy is well known, however severe odontogenic infections are rarely considered in the literature. The following case report describes the dramatic course of a deep neck space infection in a pregnant patient, commencing with typical symptoms of localized odontogenic infection and ending in a critical, life-threatening condition for the patient and a lethal condition for the foetus. The case represents the first description of intrauterine, foetal death caused by a deep neck space infection. Implications for dental and medical treatment during pregnancy, especially regarding odontogenic infections, are presented and discussed with findings in the international literature.

High sensitive thyroglobulin assay on thyroxine therapy: can it avoid stimulation test in low and high risk differentiated thyroid carcinoma patients?

Thyroglobulin (Tg) is a key marker in the follow-up of differentiated thyroid cancer (DTC). Diagnostic accuracy of serum Tg is higher after TSH stimulation than during thyroxine treatment. However, some studies suggest that TSH stimulation could be not necessary in a large part of patients, if Tg is measured by high sensitive assay under replacement therapy. The aim of this study was to evaluate the need of Tg stimulation test in DTC followed-up by sensitive Tg assay. In a prospective multicenter explorative study, 68 low or high risk patients underwent Tg measurement on thyroxine (ON-LT4-Tg) and after LT4 withdrawal (OFF-LT4-Tg). Undetectable ON-LT4-Tg and OFF-LT4-Tg values (i. e.,<0.15 ng/ml) were found in 56/68 patients, all with negative imaging workup. Twelve subjects had skewed OFF-LT4-Tg: 8 cases had increased ON-LT4-Tg and local recurrence (n=6), distant metastasis (n=1), or benign thyroglossal duct (n=1); the remaining 4 patients had undetectable ON-T4-Tg but detectable OFF-LT4-Tg and neck metastasis was recorded in one of these. By ROC analysis, the most accurate cutoff for ON-LT4-Tg and OFF-LT4-Tg were set at 0.23 ng/ml and 0.70 ng/ml, respectively. A positive ON-LT4-Tg value accurately predicts a positive stimulation test and confers an Odds Ratio of 464 (95% CI from 26.3 to 8 173.2, p<0.0001) to have persistent/recurrent disease. This study shows that DTC patients with ON-LT4-Tg below 0.23 ng/ml by our high sensitive assay should be considered disease free and they can avoid Tg stimulation test. High sensitive Tg assays should be used to better manage DTC patients.

Solving inverse problems for biological models using the collage method for differential equations.

In the first part of this paper we show how inverse problems for differential equations can be solved using the so-called collage method. Inverse problems can be solved by minimizing the collage distance in an appropriate metric space. We then provide several numerical examples in mathematical biology. We consider applications of this approach to the following areas: population dynamics, mRNA and protein concentration, bacteria and amoeba cells interaction, tumor growth.

Necrotizing periodontitis as a possible manifestation of common variable immunodeficiency.

Common variable immunodeficiency (CVID) is an inherited disease characterized by hypogammaglobulinaemia and impaired humoural immunoresponse and is mainly associated with recurrent infections of the airway and the digestive tract. An 18-year old female with a diagnosis of CVID associated with a devastating necrotizing periodontitis, ultimately resulting in complete destruction of the periodontium and loss of all teeth, is reported. Clinical, biochemical, microbiological and radiographic examinations are presented. The report highlights the likely importance of immunoglobulin replacement and intensive dental hygiene in CVID patients, and the devastating effect of non-compliance in such patients.

Point defects on graphene on metals.

Understanding the coupling of graphene with its local environment is critical to be able to integrate it in tomorrow's electronic devices. Here we show how the presence of a metallic substrate affects the properties of an atomically tailored graphene layer. We have deliberately introduced single carbon vacancies on a graphene monolayer grown on a Pt(111) surface and investigated its impact in the electronic, structural, and magnetic properties of the graphene layer. Our low temperature scanning tunneling microscopy studies, complemented by density functional theory, show the existence of a broad electronic resonance above the Fermi energy associated with the vacancies. Vacancy sites become reactive leading to an increase of the coupling between the graphene layer and the metal substrate at these points; this gives rise to a rapid decay of the localized state and the quenching of the magnetic moment associated with carbon vacancies in freestanding graphene layers.

Potential clinical role of telomere length in human glioblastoma.

Glioblastoma Multiforme (GBM) is the most common and lethal of human primary central nervous system (CNS) tumors. Due to the tumour's intrinsic clinical and molecular heterogeneity, choice of initial treatment, prediction of survival, stratification of patients, prediction and monitoring of response to therapy, represent some of the greatest challenges in the management of GBM patients. Patients, despite optimal surgery, radiation and chemotherapy, still have a median survival of 14-16 months. A reason for this dismal prognosis is because of the relative inaccuracy of current prognostic markers, so far based on clinical or pathological variables. Molecular markers that effectively predict response to therapy and survival outcomes are limited. Consequently, there is a strong need to develop novel and independent markers of prognosis. Ideal biomarkers for solid tumors would serve one or more important functions. Telomeres, guanine-rich tandem DNA repeats of the chromosomal end, provide chromosomal stability, regulates important cellular processes, and seem to be implicated in human carcinogenesis. Recently, telomeres have been shown either to be associated with clinical markers of disease progression or to be independent markers of cancer prognosis in solid tumours, including GBM. Nevertheless, a corresponding comprehensive discussion of these promising developments in brain tumours has not yet been available in the literature. Therefore, here we reviewed studies focused on the assessment of telomeric length in brain tumours with the aim to emphasized those findings indicating a potential clinical role of telomeres in GBM. With the aim to enhance the awareness of the potential clinical role of telomeres' length information in GBM, using a southern blot analysis, telomeric length in excised tumour samples was analyzed. Moreover, an attempt to correlated telomere length with patients' overall survival, was also performed. The findings here reviewed shows some contradictory results, due to different tissues used as controls, but mainly to cellular and molecular heterogeneity in GBMs that drive molecular mechanisms controlling telomere length, included telomerase and Alternative Lengthening of Telomeres (ALT), through multiple mechanisms. However, overall these studies, including our own, are consistent with the hypothesis that GBMs' telomeres were always shorter when compared with Normal Brain Tissue (NBT), and together with higher telomerase activity seem to be associated with malignancy and poor outcome; while tumours with ALT phenotype have longer telomeres, "less malignant" behaviour and better prognosis. We conclude that, although not entirely consistent in the type of telomere alteration, i.e., attrition vs. elongation, and unclear on the underlying mechanisms, multiple studies in brain tumours have shown that telomere dysfunctions are associated with parameters of clinical outcome in patients with GBMs and therefore will be part of novel risk assessment and prognostic modalities for patients with these still dismal disease.

AMEE 2009 spotlight on educational research.

The AMEE meeting is unique among the medical education conferences in that it is truly international. Educational research presented at the 2009 AMEE Meeting was both diverse and robust. In this article, we will present an overview of educational research from the meeting. We will begin with outlining our methods for the selection and categorization of themes, discuss some highpoints from some of the respective themes, and finally from the conference overall.

Insulin receptor and IGF1R are not required for oocyte growth, differentiation, and maturation in mice.

In mammals, insulin and insulin-like growth factors (IGFs: IGF1 and IGF2) act through 2 structurally related receptors, the insulin receptor (INSR) and the type 1 IGF receptor (IGF1R), both of which are expressed in developing oocytes. IGF1 plays an important role in female reproduction, and female Igf1 knockout mice fail to ovulate and are infertile. On the other hand, little is known about the in vivo role of the insulin signaling pathway in oocytes during follicular development, although exposure to insulin or IGF1 in vitro improves oocyte maturation. To further address the significance of insulin/IGF signaling, we used conditional mutant mice and ablated the function of the genes encoding INSR, IGF1R, or both receptors specifically in developing mouse oocytes. Our genetic evidence showed unexpectedly that the female reproductive functions are not affected when Insr, Igf1r or both Insr;Igf1r are ablated in oocytes, as the female mice are fertile and exhibit normal estrous cyclicity, oocyte development and maturation, parturition frequency, and litter size. In view of these novel observations indicating that the insulin/IGF signaling is not essential in oocytes, the IGF1-dependent female fertility is re-evaluated and discussed.

A qualitative evaluation of medical student learning with concept maps.

PURPOSE AND AIMS: The purpose of this study was to investigate the ways in which the use of concept maps influenced the learning processes of third year internal medicine students in the context of medical education. Reported here are the qualitative results of this study. METHODS: One-hundred thirty four medical students were taught to use concept mapping as a learning strategy at the beginning of their internal medicine rotations. Upon completion of the internal medicine rotation students were asked to evaluate how concept maps fostered the process of linking theoretical information to clinical practice. Additionally, students described how concept maps impacted their learning. RESULTS: In this study, concept maps fostered a positive connection between theory and practice. Additionally, students described three major themes impacting their learning: concept mapping as a facilitator of knowledge integration and critical thinking, as a teaching methodology and finally, as a learning method. CONCLUSIONS: This study suggests concept maps may be an instructional method to foster the learning and thinking process of medical students.