Determinants Of Drug Utilisation During Childhood

Paediatric pharmacology is a neglected area in terms of rational use of drugs. Wide differences have been observed in children’s exposure to drugs between and within countries and regions. The aim of the current thesis is to investigate the determinants of drug prescription in paediatrics. Pharmacoepidemiology and the use of administrative databases can be a useful tool for this scope. Data collected in regional and multiregional administrative prescription databases were analysed. Prevalence data by sex and age were calculated by dividing the number of drug users by the total number of male and female residents in each age group. Univariable and multivariable analyses were performed with the aim to identify the determinants of drug prescriptions. The studies showed quantitative and qualitative differences in drug prescription to children and adolescents among Italian regions and within regions. The prescription of a great number of different, redundant, active substances, even among experienced paediatricians, was found. A North-South trend was found in antiasthmatic and antibiotic prevalence, with an important association with average income at the area level. A confirmation of the high prevalence of these drugs and poor qualitative profile was also found. Large heterogeneity was found in psychotropic drug prevalence among different Italian regions. Psychotropic drugs were scantly prescribed and some of the most used drugs were prescribed off-label. The analyses of the prescription of generic antibiotics showed that generic formulations are scantly prescribed by Italian paediatricians, and the lowest prescription rate of generic drugs was found in paediatricians who prescribe more antibiotics. Some quality indicators for antibiotic prescribing were developed at the paediatrician level. The youngest paediatricians and those who were not exposed to educational interventions showed a significantly worse quality of prescribing. The thesis provide some useful data for policy makers in order to improve the rational drug use in children

Escollos y peligros del análisis de supervivencia: el caso de los datos de COVID-19: English

Non-parametric survival analysis has become a very popular statistical method in current medical research. However, resorting to survival analysis when its fundamental assumptions are not fulfilled can severely bias the results. Currently, hundreds of clinical studies are using survival methods to investigate factors potentially associated with the prognosis of coronavirus disease 2019 (COVID-19) and test new preventive and therapeutic strategies.In the pandemic era, it is more critical than ever to base decision-making on evidence and rely on solid statistical methods, but this is not always the case. Serious methodological errors have been identified in recent seminal studies about COVID-19: One reporting outcomes of patients treated with remdesivir and another one on the epidemiology, clinical course, and outcomes of critically ill patients.High-quality evidence is essential to inform clinicians about optimal COVID-19 therapies and policymakers about the true effect of preventive measures aiming to tackle the pandemic. Though timely evidence is needed, we should encourage the appropriate application of survival analysis methods and careful peer-review to avoid publishing flawed results, which could affect decision-making.In this paper, we recapitulate the basic assumptions underlying non-parametric survival analysis and frequent errors in its application and discuss how to handle data on COVID-19.El análisis de supervivencia es un método estadístico muy popular en la investigación médica actual. Sin embargo, el recurrir al análisis de supervivencia cuando no se cumplen sus supuestos fundamentales puede sesgar gravemente los resultados. Actualmente, cientos de estudios clínicos están utilizando esta metodología para estudiar los factores potencialmente asociados con el pronóstico de la COVID-19 y probar nuevas estrategias preventivas y terapéuticas.En la pandemia actual es más importante que nunca que las decisiones se basen en pruebas y en métodos estadísticos sólidos. Sin embargo, este no es siempre el caso. Se han detectado errores metodológicos graves en estudios seminales recientes sobre COVID-19: uno que informa los resultados de los pacientes tratados con remdesivir y otro sobre la epidemiología, el curso clínico y los resultados de los pacientes críticamente enfermos.La evidencia de calidad es esencial para informar a los médicos sobre las terapias óptimas ontra la enfermedad y, a los legisladores, sobre el verdadero efecto de las medidas preventivas destinadas a abordar la pandemia. Aunque se necesitan pruebas oportunas, debemos fomentar la aplicación adecuada de los métodos de análisis de supervivencia y una cuidadosa revisión por pares para evitar la publicación de resultados defectuosos que pueden afectar la adopción de decisiones.En este artículo, recapitulamos los supuestos básicos que subyacen al análisis de supervivencia y los errores frecuentes en su aplicación, y discutimos cómo manejar los datos sobre la COVID-19

Use of proton pump inhibitors and risk of gastric cancer

View full abstracthttps://openworks.mdanderson.org/leading-edge/1004/thumbnail.jp

Multiple outcome meta-analysis of gene-expression data in inflammatory bowel disease

We performed a multivariate meta-analysis of microarray data in Crohn's disease (CD) and Ulcerative colitis (UC), which are the main forms of inflammatory bowel disease (IBD). They share similar symptoms but differ in the location and extent of inflammation and in complications. We identified 249 differentially expressed genes (DEGs) in CD and 38 in UC at a false discovery rate of 1%. 20 of the DEGs were common to both diseases. A multivariate test identified 260 DEGs associated with IBD, 53 of which were not found in any of the disorders. We identified important molecular pathways implicated in the pathogenesis of IBD, such as the JAK/STAT and interferon-gamma signaling pathways, genes involved in cell adhesion, apoptosis and carcinogenesis. Among others, BCAT1 and GZMB are interesting novel DEGs that deserve further investigation in experimental models. The method could also be useful to other cases of meta-analysis of gene expression data

Click-Chemistry Cross-Linking of Hyaluronan Graft Copolymers

An easy and viable crosslinking procedure by click-chemistry (click-crosslinking) of hyaluronic acid (HA) was developed. In particular, the clickable propargyl groups of hyaluronane-based HA-FA-Pg graft copolymers showing low and medium molecular weight values were exploited in crosslinking by click-chemistry by using a hexa(ethylene glycol) spacer. The resulting HA-FA-HEG-CL materials showed an apparent lack of in vitro cytotoxic effects, tuneable water affinity, and rheological properties according to the crosslinking degree that suggests their applicability in different biomedical fields

Reply to Ghirardello et al Letter to the Editor

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Validation of a new optical diagnosis training module to improve dysplasia characterization in inflammatory bowel disease:a multicenter international study

Background and aims Inflammatory bowel disease (IBD) increases risk of dysplasia and colorectal cancer. Advanced endoscopic techniques allow for the detection and characterization of IBD dysplastic lesions, but specialized training is not widely available. We aim to develop and validate an online training platform to improve the detection and characterization of colonic lesions in IBD: OPTIC-IBD. Methods We designed a web-based learning module that includes surveillance principles, optical diagnostic methods, approach to characterization, classifications of colonic lesions, utilizing still images and videos. We invited gastroenterologists from Canada, Italy, and the UK, with a wide range of experience. Participants reviewed 24 educational videos of IBD colonic lesions, predicted histology, and rated their confidence. The primary endpoint was to improve accuracy in detecting dysplastic lesions following training on the platform. Furthermore, participants were randomized 1:1 to get additional training or not, with a final assessment occurring after 60 days. Diagnostic performance for dysplasia and rater confidence were measured. Results One hundred seventeen participants completed the study and were assessed for the primary endpoint. Diagnostic accuracy improved from 70.8% to 75.0% (p 0.002) following training, with the greatest improvements seen in less experienced endoscopists. Improvements in both accuracy and confidence were sustained after 2 months of assessment, although the group randomized to receive additional training did not improve further. Similarly, participants’ confidence in characterizing lesions significantly improved between pre- and post-course (

Use of biologics for the management of Crohn's disease: IG-IBD clinical guidelines based on the GRADE methodology

A cure for Crohn's disease (CD), a chronic inflammatory disease of the gastrointestinal tract of unknown etiology, is not available, so patients require lifelong management to keep inflammation under control. The therapeutic armamentarium has expanded with approval of several biological drugs, including in-fliximab, adalimumab, vedolizumab and ustekinumab - monoclonal antibodies that target different in-flammatory pathways - and darvadstrocel, a suspension of expanded human allogeneic, adipose-derived, mesenchymal stromal cells for the treatment of refractory complex perianal fistula. Notwithstanding ex-isting practice guidelines on medical therapy for CD, the Italian Group for the Study of Inflammatory Bowel Disease felt the need to issue new guidelines focused on the use of biologics for managing the intestinal manifestations of CD and based on the GRADE methodology. This document presents recom-mendations regarding six clinical settings, from the induction to the maintenance of clinical remission, and from optimization and de-escalation of treatments to dealing with perianal CD and post-operative recurrence. The 19 evidence-based statements are supported by information on the quality of the evi-dence, agreement rate among panel members, and panel comments mainly based on evidence from real world studies

Autoimmune polyglandular syndrome type 4: experience from a single reference center

Purpose: To characterize patients with APS type 4 among those affected by APS diagnosed and monitored at our local Reference Center for Autoimmune Polyglandular Syndromes. Methods: Monocentric observational retrospective study enrolling patients affected by APS diagnosed and monitored in a Reference Center. Clinical records were retrieved and analyzed. Results: 111 subjects (51 males) were affected by APS type 4, mean age at the onset was 23.1 ± 15.1 years. In 15 patients the diagnosis of APS was performed during the first clinical evaluation, in the other 96 after a latency of 11 years (range 1-46). The most frequent diseases were type I diabetes mellitus and celiac disease, equally distributed among sexes. Conclusions: The prevalence of APS type 4 is 9:100,000 people. Type I diabetes mellitus was the leading indicator of APS type 4 in 78% subjects and in 9% permitted the diagnosis occurring as second manifestation of the syndrome. Our data, showing that 50% of patients developed APS type 4 within the first ten years, don't suggest any particular follow-up time and, more importantly, don't specify any particular disease. It is important to emphasize that 5% of women developed premature ovarian failure

The Effect of Adjuvant Radiotherapy on One- and Two-Stage Prosthetic Breast Reconstruction and on Autologous Reconstruction: A Multicenter Italian Study among 18 Senonetwork Breast Centres

Purpose: In modern breast cancer treatment, a growing role has been observed for breast reconstruction together with an increase in clinical indications for postmastectomy radiotherapy (PMRT). Choosing the optimum type of reconstructive technique is a clinical challenge. We therefore conducted a national multicenter study to analyze the impact of PMRT on breast reconstruction. Methods: We conducted a retrospective case-control multicenter study on women undergoing breast reconstruction. Data were collected from 18 Italian Breast Centres and stored in a cumulative database which included the following: autologous reconstruction, direct-to-implant (DTI), and tissue expander/immediate (TE/I). For all patients, we described complications and surgical endpoints to complications such as reconstruction failure, explant, change in type of reconstruction, and reintervention. Results: From 2001 to April 2020, 3116 patients were evaluated. The risk for any complication was significantly increased in patients receiving PMRT (aOR, 1.73; 95% CI, 1.33-2.24; p < 0.001). PMRT was associated with a significant increase in the risk of capsular contracture in the DTI and TE/I groups (aOR, 2.24; 95% CI, 1.57-3.20; p < 0.001). Comparing type of procedures, the risk of failure (aOR, 1.82; 95% CI, 1.06-3.12, p=0.030), explant (aOR, 3.34; 95% CI, 3.85-7.83, p < 0.001), and severe complications (aOR, 2.54; 95% CI, 1.88-3.43, p < 0.001) were significantly higher in the group undergoing DTI reconstruction as compared to TE/I reconstruction. Conclusion: Our study confirms that autologous reconstruction is the procedure least impacted by PMRT, while DTI appears to be the most impacted by PMRT, when compared with TE/I which shows a lower rate of explant and reconstruction failure. The trial is registered with NCT04783818, and the date of registration is 1 March, 2021, retrospectively registered