Data collected in the European Cystic Fibrosis Society Patient Registry (ECFSPR) database were used to investigate whether risk factors for death in childhood and adolescents CF patients have ...different impact in countries of different income. In this way, it is possible to recognize where interventions could improve the quality of care and survival in these patients. We matched deceased and alive patients by age, country, year of follow-up. Multivariable logistic models were developed. In the years of this study, the ECFSPR collected information on 24,416 patients younger than 18 years: 7830 patients were from countries with low/middle income and 16,586 from countries with high income; among these the dead are 102 and 107 (
< 0.001), respectively. The use of oxygen, forced expiratory volume in one second (FEV₁) below 40% and BMI standard deviation score (SDS) below -2 represent risk factors for death. However, some patients from countries with high income remain alive even if their values of FEV₁% and BMI-SDS were low, and some deceased patients from countries with high income had high values of FEV₁% (>60%). Evaluation of mortality in pediatric age may reflect the availability of resources for CF diagnosis and treatment in some countries.
This exercise can be given to a group of students with basic knowledge of mathematics and physics at the beginning of a lesson. We can imagine that there will be some students that will solve the ...exercise using the “common sense” solution recalling basic notions of physics and some students that will solve the exercise recalling basic notion of physics and computing a mean velocity using the arithmetic mean, the most common mean. At the end of the exercise, the teacher will compare the two solutions and will present the harmonic mean as the fastest solution for the students that solved the problem using the “common sense” solution and as the correct mean to be used for the students that solved the exercise computing a mean velocity
Restoration of BECN1/Beclin 1-dependent autophagy and depletion of SQSTM1/p62 by genetic manipulation or autophagy-stimulatory proteostasis regulators, such as cystamine, have positive effects on ...mouse models of human cystic fibrosis (CF). These measures rescue the functional expression of the most frequent pathogenic CFTR mutant, F508del, at the respiratory epithelial surface and reduce lung inflammation in Cftr
F508del
homozygous mice. Cysteamine, the reduced form of cystamine, is an FDA-approved drug. Here, we report that oral treatment with cysteamine greatly reduces the mortality rate and improves the phenotype of newborn mice bearing the F508del-CFTR mutation. Cysteamine was also able to increase the plasma membrane expression of the F508del-CFTR protein in nasal epithelial cells from F508del homozygous CF patients, and these effects persisted for 24 h after cysteamine withdrawal. Importantly, this cysteamine effect after washout was further sustained by the sequential administration of epigallocatechin gallate (EGCG), a green tea flavonoid, both in vivo, in mice, and in vitro, in primary epithelial cells from CF patients. In a pilot clinical trial involving 10 F508del-CFTR homozygous CF patients, the combination of cysteamine and EGCG restored BECN1, reduced SQSTM1 levels and improved CFTR function from nasal epithelial cells in vivo, correlating with a decrease of chloride concentrations in sweat, as well as with a reduction of the abundance of TNF/TNF-alpha (tumor necrosis factor) and CXCL8 (chemokine C-X-C motif ligand 8) transcripts in nasal brushing and TNF and CXCL8 protein levels in the sputum. Altogether, these results suggest that optimal schedules of cysteamine plus EGCG might be used for the treatment of CF caused by the F508del-CFTR mutation.
Background: There is a large heterogeneity among the courses of medical statistics in Italian Medical Schools.
Aims: (1) To describe issues that are dealt with in the statistics undergraduate ...medical courses in Italian medical Schools. (2) To investigate which methodological topics are deemed as more useful for the education of undergraduate medical students by clinical teachers.
Methods: (1) An online questionnaire, covering the qualifying teaching issues of medical statistics, was sent to all academic biostatisticians, asking what they were teaching to undergraduate medical students. The reference year was 2015-2016. Undergraduate medical courses were the statistical units. (2) A second survey involved teachers of other medical disciplines with institutional roles, asking to score the usefulness for medical education of a number of topics concerning medical statistics, on a 5-point Likert scale. Only descriptive analyses were performed.
Results: Fifty-two (96%) case report forms (CRF) were returned from teachers of medical statistics. Most statistical and epidemiological topics were taught except comparison of >2 groups, impact of biases and standardization of rates. Conversely, issues of clinical epidemiology were neglected in about half of degree courses.
Thirty-three (31%) CRFs were returned from clinical teachers. The percentage of issues deemed very useful or essential ranged from 57% to 94%, with higher scores for those referring to critical assessment of the literature.
Conclusions: More extensive coverage of clinical epidemiology issues is needed to meet the demand of physicians, as responsible consumers of quantitative research. As biostatisticians we should operate to increase the homogeneity of medical statistics teaching in medical undergraduates’ education
We investigated the relationship between the International Prognostic Scoring System of the International Working Group for Myelofibrosis Research and Treatment and the European Consensus on grading ...of bone marrow fibrosis (MF) in patients with primary myelofibrosis. We compared them in 196 consecutive primary myelofibrosis patients (median follow-up 45.7 months; range 7.4–159). International Prognostic Scoring System classified 42 cases as low risk, 73 as intermediate risk-1, 69 as intermediate risk-2, and 12 as high risk; European Consensus on grading of bone marrow fibrosis classified 83 cases as MF-0, 58 as MF-1, 41 as MF-2, and 14 as MF-3. By the time of the analysis, 30 patients (15.3%) had died. Overall median survival was 3.8 years (95% confidence interval: 3.3–4.3). Multivariate analysis confirmed that both scoring systems independently predicted survival, with hazard ratios similar to those provided by univariate analysis (respectively, 2.40 (95% confidence interval: 1.47–3.91) and 2.58 (95% confidence interval: 1.72–3.89) but the likelihood ratio increased from 19.6 of the International Prognostic Scoring System or 29.0 of the European Consensus on grading of bone MF to 42.3 when both measures were considered together. Analysis of the overall survival curves documented that patients classified as having the most favourable rate with both prognostic scores (ie low risk and MF-0) survive longer than those with only one favourable score (ie low risk but MF >0 or MF-0, but International Prognostic Scoring System >low risk). In contrast, those patients classified as having the most unfavourable rate for both scores (high risk and MF-3) have a shorter survival than those with only one unfavourable score (ie high risk but MF<3 or MF-3, but International Prognostic Scoring System <high risk). In conclusion, our analysis suggests that better prognostication can be achieved in primary myelofibrosis patients when both systems are used together.
Aims
To evaluate whether a comprehensive histological evaluation of reticulin fibrosis, collagen deposition and osteosclerosis in bone marrow trephine biopsies (BMBs) of primary myelofibrosis (PMF) ...patients may have prognostic implications.
Methods and results
Reticulin fibrosis, collagen deposition and osteosclerosis were graded from 0 to 3 in a series of 122 baseline BMBs. Then, we assigned to each case a comprehensive score reticulin, collagen, osteosclerosis (RCO) score, ranging from 0 to 9 that allowed us to distinguish two groups of patients, with low‐grade (RCO score 0–4) and high‐grade (RCO score 5–9) stromal changes. Of 122 patients, 88 displayed a low‐grade and 34 a high‐grade RCO score. The latter was associated more frequently with anaemia, thrombocytopenia, peripheral blood blasts and increased lactate dehydrogenase levels. The RCO score was correlated strictly with overall mortality (P = 0.013) and International Prognostic Scoring System (IPSS) risk categories, and was able to discriminate the overall survival of both low‐ and high‐grade patients (log‐rank test: P < 0.001). Moreover, it proved to be more accurate than the European Consensus on Grading of Bone Marrow Fibrosis (ECGMF grade) in identifying high‐risk patients with poor prognosis. Finally, a combined analysis of RCO scores and IPSS risk categories in an integrated clinical–pathological evaluation was able to increase the positive predictive value (PPV) for mortality in high‐risk patients.
Conclusion
The comprehensive RCO score, obtained by histological evaluation of reticulin fibrosis, collagen deposition and osteosclerosis was prognostically significant and more accurate than ECGMF grade in identifying high‐risk patients and improved PPV when applied in addition to IPSS.
Salmonella enterica serotype Napoli (S. Napoli) is currently emerging in Europe and particularly in Italy, where in 2014 it caused a large outbreak associated with elevated rates of bacteremia. ...However, no study has yet investigated its invasive ability and phylogenetic classification. Here, we show that between 2010 and 2014, S. Napoli was the first cause of invasive salmonellosis affecting 40 cases out of 687 (invasive index: 5.8%), which is significantly higher than the invasive index of all the other nontyphoidal serotypes (2.0%, p < 0.05). Genomic and phylogenetic analyses of an invasive isolate revealed that S. Napoli belongs to Typhi subclade in clade A, Paratyphi A being the most related serotype and carrying almost identical pattern of typhoid-associated genes. This work presents evidence of invasive capacity of S. Napoli and argues for reconsideration of its nontyphoidal category.
Abstract Background The existence of gender-related differences since childhood in survival of cystic fibrosis (CF) patients has been recently challenged. Methods We evaluated the effect of gender on ...survival of 2293 CF patients born after 01/01/1988, followed up by 29 CF centres until 31/12/2004 and recorded in the Italian Registry for CF (IRCF). Results We observed similar annual mortality rates in females (3.59‰) and males (4.00‰), similar survival curves (log-rank test p = 0.64) and similar hazards of death (hazard ratio adjusted for presence of symptoms at diagnosis, meconium ileus, F508del mutation and age at diagnosis: 1.29, 95%CI: 0.60; 2.76). However, excess mortality due to CF was higher for females (5.9) than males (5.1). Conclusions In our population CF females do not experience higher mortality than males but, due to the disease, they lose the expected survival advantage occurring in the general population at this age. We do not exclude, however, that differences in mortality will establish after adolescence.
To evaluate the effect of allergic bronchopulmonary aspergillosis (ABPA) on FEV
percent predicted in children and adolescents with cystic fibrosis.
Longitudinal data analysis (2008-2010).
Patients ...participating in the European Cystic Fibrosis Society Patient Registry.
3350 patients aged 6-17 years.
FEV
percent predicted was the main outcome measure (one measurement per year per child). To describe the effect of ABPA (main explanatory variable) on FEV
while controlling for other prognostic factors, a linear mixed effects regression model was applied.
In 2008, the mean (±SD) FEV
percent predicted was 78.6 (±20.6) in patients with ABPA (n=346) and 88 (±19.8) in those without ABPA (n=2806). After considering other variables, FEV
in subjects with ABPA on entry to the study was 1.47 percentage points lower than FEV
in patients of similar age without ABPA (p=0.003). There was no FEV
decline associated with ABPA over the subsequent study years as the interaction of ABPA with age was not significant (p>0.05). For patients aged 11.82 years (population mean age), poor body mass index had the greatest impact on FEV
in 2008, followed by high-risk genotype (two severe mutations), female gender, diabetes mellitus, chronic
infection and ABPA in descending order of effect size.
In contrast to the common clinical belief of ABPA having a serious impact on lung function, the difference in FEV
between young patients with and without the complication was found to be modest when the effect of other prognostic factors was considered.
In this study, we investigate in detail the morphological, clinical and molecular features of 71 consecutive patients with a diagnosis of myeloproliferative neoplasms, unclassifiable. We performed a ...meticulous morphological analysis and found that most of the cases displayed a hypercellular bone marrow (70%) with normal erythropoiesis without left-shifting (59%), increased granulopoiesis with left-shifting (73%) and increased megakaryocytes with loose clustering (96%). Megakaryocytes displayed frequent giant forms with hyperlobulated or bulbous nuclei and/or other maturation defects. Interestingly, more than half of the cases displayed severe bone marrow fibrosis (59%). Median values of hemoglobin level and white blood cells count were all within the normal range; in contrast, median platelets count and lactate dehydrogenase were increased. Little less than half of the patients (44%) showed splenomegaly. JAK2V617F mutation was detected in 72% of all patients. Among the JAK2-negative cases, MPLW515L mutation was found in 17% and CALR mutations in 67% of the investigated cases, respectively. Finally, by multiple correspondence analysis of the morphological profiles, we found that all but four of the cases could be grouped in three morphological clusters with some features similar to those of the classic BCR-ABL1-negative myeloproliferative neoplasms. Analysis of the clinical parameters in these three clusters revealed discrepancies with the morphological profile in about 55% of the patients. In conclusion, we found that the category of myeloproliferative neoplasm, unclassifiable is heterogeneous but identification of different subgroups is possible and should be recommended for a better management of these patients.
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