Patients' perceptions of quality of care delivery by urology residents: A nationwide study.

OBJECTIVE: To present the results of a nationwide survey among urological patients to evaluate their perception of the quality of care provided by residents. METHODS: An anonymous survey was distributed to patients who were referred to 22 Italian academic institutions. The survey aimed to investigate the professional figure of the urology resident as perceived by the patient. RESULTS: A total of 2587 patients were enrolled in this study. In all, 51.6% of patients were able to correctly identify a urology resident; however, almost 40% of respondents discriminated residents from fully trained urologists based exclusively on their young age. Overall, 98.2% patients rated the service provided by the resident as at least sufficient. Urology trainees were considered by more than 50% of the patients interviewed to have good communication skills, expertise and willingness. Overall, patients showed an excellent willingness to be managed by urology residents. The percentage of patients not available for this purpose showed an increasing trend that directly correlated with the difficulty of the procedure. Approximately 5-10% of patients were not willing to be managed by residents for simple procedures such as clinical visits, cystoscopy or sonography, and up to a third of patients were not prepared to undergo any surgical procedure performed by residents during steps in major surgery, even if the residents were adequately tutored. CONCLUSIONS: Our data showed that patients have a good willingness to be managed by residents during their training, especially for medium- to low-difficulty procedures. Furthermore, the majority of patients interviewed rated the residents' care delivery as sufficient. Urology trainees were considered to have good communication skills, expertise and willingness.

Asthma in the Real-World: The Relevance of Gender.

BACKGROUND: The possible gender impact on asthma arouses current and outstanding interest, but few studies addressed this issue in the real-world setting. OBJECTIVE: This cross-sectional study tested the hypothesis of a potential difference between asthmatic males and females in a real-life setting, such as a third-level asthma clinic. METHODS: A total of 499 asthmatic outpatients (301 females and 198 males, mean age 58.25 years) were consecutively visited. The visit included history, asthma control, and severity grade, physical examination, lung function, fractional exhaled nitric oxide assessment, and blood sample for biomarkers. RESULTS: There were more females than males (about 3 of 5). Asthmatic females smoked less (p < 0.0001) than males and had higher FEV1 (p = 0.0022) and FVC (p = 0.0004) values than asthmatic males. CONCLUSIONS: Gender difference was associated with smoking and lung function impairment; thus, this issue should be carefully considered in asthmatic patients in daily clinical practice.

Awareness of European practitioners toward uncommon tropical diseases: are we prepared to deal with mass migration? Results of an international survey.

PURPOSE: The recent rise in migration from Africa through the Mediterranean basin into Europe has resulted in an increased incidence of uncommon diseases such as schistosomiasis and genito-urinary tuberculosis, which were previously largely unknown in this region. This study aimed to evaluate the insight of European urologists into diagnosing and managing these disease conditions and to determine whether they were adequately prepared to deal with the changing disease spectrum in their countries. METHODS: A survey including specific questions about the diagnosis and management of 'tropical' urological diseases was distributed among urologists working in Europe and Africa. Multivariate logistic regression models were performed to detect the continent (African or European) effect on knowledge of and insight into tropical urological diseases. RESULTS: A total of 312 surveys were administered. African and European respondents accounted for 109 (36.09%) and 193 (63.91%) respondents, respectively. The multivariate logistic regression analysis demonstrated a significant deficiency in the knowledge of tropical urological diseases in the European cohort compared with the African cohort (p < 0.05). Moreover, in the European cohort, markedly superior knowledge of tropical urological diseases was observed for respondents who had previously worked in a developing country. CONCLUSIONS: Though European urologists are not required to have the same insight as African urologists, they showed a very unsatisfactory knowledge of tropical urological diseases. The experience of working in a developing country could improve the knowledge of European urologists regarding tropical urological diseases.

A real-world assessment of asthma with chronic rhinosinusitis.

BACKGROUND: Chronic rhinosinusitis (CRS) includes 2 main phenotypes: CRS without nasal polyps (CRSsNP) and CRS with nasal polyps (CRSwNP). CRS has been reported to be a comorbidity of asthma. OBJECTIVE: This study aimed to investigate the role of CRS in outpatients with asthma visited in real-world setting. METHODS: This cross-sectional study enrolled 499 consecutive outpatients with asthma. Age, sex, body mass index, smoking status, lung function, Asthma Control Test, inflammatory type 2 biomarkers (including fractional exhaled nitric oxide, blood eosinophils, serum total immunoglobulin E, and allergy), treatment step according to the Global Initiative for Asthma, and comorbidities (obstructive sleep apnea syndrome, arterial hypertension, bronchiectasis, diabetes mellitus type 2, and osteoporosis) were evaluated. RESULTS: A total of 179 (35.87%) patients had CRS, in particular 93 (18.64%) had CRSsNP and 86 (17.23%) had CRSwNP. Type 2 inflammation (defined by at least 1 positive biomarker) was present in 81.44% of patients (fractional exhaled nitric oxide > 30 parts per billion in 46.9%, blood eosinophil count > 300 cell/µL in 39.67%, serum total immunoglobulin E >100 IU/mL in 51.54%, and allergy in 53.71%). By multivariate analysis, type 2 inflammation and blood eosinophils greater than 300 cell/µL were the main predictors (odds ratio [OR] 2.54 and 2.26, respectively) of CRS-asthma association. In particular, CRSwNP comorbidity was predicted by type 2 inflammation (OR 3.4) and blood eosinophils greater than 300 cell/µL (OR 3.0). Smoking had conflicting outcome. CONCLUSION: This study confirmed that CRS is a frequent asthma comorbidity because it affects more than one-third of outpatients with asthma. CRSwNP is associated with type 2 inflammation and blood eosinophilia. These outcomes underline that CRSwNP asthma phenotype deserves adequate attention for careful management and optimal identification of the best-tailored therapy.

Evaluation of bradykinin, VEGF, and EGF biomarkers in gingival crevicular fluid and comparison of PhotoBioModulation with conventional techniques in periodontitis: a split-mouth randomized clinical trial.

Periodontal disease is a chronic progressive inflammatory process leading to damage of tooth-supporting tissues. This comparative study assessed the effect of PhotoBioModulation (PBM) versus conventional therapy, and investigated biomarkers involved in the healing process. The test group comprised twenty systemically-healthy non-smoking subjects with chronic periodontitis with the presence of two matched contro-lateral premolar sites (probing depth > 5 mm); twenty subjects without chronic periodontitis (CP) served as control group. Patients were treated at baseline, either with scaling and root planing (SRP group) or with a procedure entailing SRP supported by PBM (PBM group). The laser used was a diode laser operating at 645 nm wavelength, 10 J/cm2, and 0.5 W/cm2 with a 600 µm fiber optic. Crevicular fluid levels of bradykinin (BK), vascular endothelial growth factor (VEGF), and epidermal growth factor z (EGF) were determined at both sites. Crevicular fluid specimens from both groups were analyzed with the ELISA TEST. Clinical differences in analyzed outcomes were observed in favor of PBM treatment. Taking average values as 100%, the reduction in BK concentration was 47.68% with SRP and 68.43% with PBM on day 3; the VEGF concentration decreased by 35.73% with SRP and 48.59% with PBM on day 7; the EGF concentration increased by 55.58% with SRP and by 58.11% with PBM on day 21.Clinical parameters improved significantly in both groups (pooled mean values of probing depth decreased from 5.6 to 4.5 mm; gingival index from 1.92 to 1.1; and bleeding on probing from 49.67 to 23.23) but did not vary significantly between the PBM and the SRP group. The results confirmed that PBM have beneficial effects in the early phases of the healing process playing a role in modulation of BK, EGF, and VEGF in gingival crevicular fluid levels; both groups had significant clinical improvement over control but there was no significant difference between them, only a trend for PBM group. The overall results of the study suggest a potential benefit of PBM in conjunction with SRP in treating chronic periodontitis.

Determinants of therapy switch in multiple sclerosis treatment-naïve patients: A real-life study.

BACKGROUND: With many options now available, first therapy choice is challenging in multiple sclerosis (MS) and depends mainly on neurologist and patient preferences. OBJECTIVES: To identify prognostic factors for early switch after first therapy choice. METHODS: Newly diagnosed relapsing-remitting MS patients from 24 Italian centers were included. We evaluated the association of baseline demographics, clinical, and magnetic resonance imaging (MRI) data to the switch probability for lack of efficacy or intolerance/safety with a multivariate Cox analysis and estimated switch rates by competing risks models. RESULTS: We enrolled 3025 patients. The overall switch frequency was 48% after 3 years. Switch risk for lack of efficacy was lower with fingolimod (hazard ratio (HR) = 0.50; p = 0.009), natalizumab (HR = 0.13; p < 0.001), dimethyl-fumarate (HR = 0.60; p = 0.037), teriflunomide (HR = 0.21; p = 0.031) as compared to interferons. Younger age (HR = 0.96; p < 0.001), diagnosis delay (HR = 1.23; p = 0.021), higher baseline Expanded Disability Status Scale (HR = 1.17; p = 0.001), and spinal cord lesions (HR = 1.46; p = 0.001) were independently associated with higher inefficacy switch rates. We found lower switch for intolerance/safety with glatiramer acetate (HR = 0.61; p = 0.001), fingolimod (HR = 0.35; p = 0.002), and dimethyl-fumarate (HR = 0.57; p = 0.022) as compared to interferons, while it increased with natalizumab (HR = 1.43; p = 0.022). Comorbidities were associated with intolerance switch (HR = 1.28; p = 0.047). CONCLUSION: Several factors are associated with higher switch risk in patients starting a first-line therapy and could be integrated in the decision-making process of first treatment choice.

Identification of IL-17F/frequent exacerbator endotype in asthma.

BACKGROUND: Severe asthma might be associated with overexpression of Th17 cytokines, which induce neutrophil recruitment via neutrophil-mobilizing cytokines in airways. OBJECTIVE: To study IL-17-related cytokines in nasal/bronchial biopsies from controls and mild asthmatics (MAs) to severe asthmatics (SAs) in relation to exacerbation rate. METHODS: Inflammatory cells and IL-17A+, IL-17F+, IL-21+, IL-22+, and IL-23+ cells were examined by immunohistochemistry in cryostat sections of bronchial/nasal biopsies obtained from 33 SAs (21 frequent exacerbators [FEs]), 31 MAs (3 FEs), and 14 controls. IL-17F protein was also measured by ELISA in bronchial/nasal lysates and by immunohistochemistry in bronchial tissue obtained from subjects who died because of fatal asthma. Immunofluorescence/confocal microscopy was used for IL-17F colocalization. RESULTS: Higher number (P < .05) of neutrophils, IL-17A+, IL-17F+, and IL-21+ cells in bronchial biopsies and higher numbers (P < .01) of IL-17F+ and IL-21+ cells in nasal biopsies were observed in SAs compared with MAs. Bronchial IL-17F+ cells correlated with bronchial neutrophils (r = 0.54), exacerbation rate (r = 0.41), and FEV1 (r = -0.46). Nasal IL-17F+ cells correlated with bronchial IL-17F (r = 0.35), exacerbation rate (r = 0.47), and FEV1 (r = -0.61). FEs showed increased number of bronchial neutrophils/eosinophils/CD4+/CD8+ cells and bronchial/nasal IL-17F+ cells. Receiver operating characteristic curve analysis evidenced predictive cutoff values of bronchial neutrophils and nasal/bronchial IL-17F for discriminating between asthmatics and controls, between MAs and SAs and between FEs and non-FEs. IL-17F protein increased in bronchial/nasal lysates of SAs and FEs and in bronchial tissue of fatal asthma. IL-17F colocalized in CD4+/CD8+ cells. CONCLUSIONS: IL-17-related cytokines expression was amplified in bronchial/nasal mucosa of neutrophilic asthma prone to exacerbation, suggesting a pathogenic role of IL-17F in FEs.

Fractional Exhaled Nitric Oxide: A Potential Biomarker in Allergic Rhinitis?

BACKGROUND: The fractional concentration of exhaled nitric oxide (FeNO) is a surrogate biomarker for Th2-dependent bronchial inflammation. The present study investigated whether FeNO may characterize allergic rhinitis (AR) patients. METHODS: A total of 553 AR patients (497 males, mean age 28.8 years) were evaluated. Those patients with a high FeNO underwent a 2-year follow-up. RESULTS: Increased FeNO was associated with a significantly longer AR duration, impaired lung function, more severe symptoms, and more frequent bronchial hyperresponsiveness (BHR). At follow-up, 22 out of 82 patients (26.8%) with high FeNO levels (>50 ppb) developed asthma. CONCLUSIONS: AR patients may frequently have high FeNO values, exceeding 50 ppb. This might be associated with an initial impaired lung function, BHR, a perceived worsening of respiratory symptoms, and potential progression to asthma.

Assessing long-term prognosis improvement as a consequence of treatment pattern changes in MS.

OBJECTIVE: To assess whether the age at which multiple sclerosis (MS) patients reach Expanded Disability Status Scale (EDSS) milestones changed as long as new drugs for the treatment of MS became available. METHODS: We evaluated the long-term impact of therapies on disability progression assessing whether there is a detectable delay in the age at which patients reached EDSS milestones in more recent years. We used data collected over more than 30 years in the Center of Brescia, Italy. We compared the age at EDSS = 6 among patients diagnosed with relapsing-remitting MS in different time periods, adjusting for age at diagnosis and median interval among EDSS visits, by a multivariate Cox model. RESULTS: A total of 1324 MS patients were included. Patients diagnosed in more recent periods reached EDSS = 6 at an older age: the rate at which patients reached EDSS = 6 in those diagnosed in 1991-1995 was similar to those diagnosed in 1980-1990 (hazard ratio ( HR) = 1.09, p = 0.68) and to those diagnosed in 1996-2000 ( HR = 0.85, p = 0.44), it was reduced by 37% in patients diagnosed in 2001-2005 ( HR = 0.63, p = 0.05), by 46% in patients diagnosed in 2006-2010 ( HR = 0.54, p < 0.02). CONCLUSION: A clear modification of MS course is observed after 2000; among other causes, this can be associated to the changes in the treatment patterns experienced in those years.

Intrarater and Inter-rater Reliability of Active Cervical Range of Motion in Patients With Nonspecific Neck Pain Measured With Technological and Common Use Devices: A Systematic Review With Meta-regression.

OBJECTIVES: The purpose of this systematic review was to compare intrarater and inter-rater reliability of active cervical range of motion (ACROM) measures obtained with technological devices to those assessed with low-cost devices in patients with nonspecific neck pain. As a secondary outcome, we investigated if ACROM reliability is influenced by the plane of the assessed movement. METHODS: Medline, Scopus, Embase, the Cochrane Library, CINHAL, PEDro, and gray literature were searched until August 2016. Inclusion criteria were reliability design, population of adults with nonspecific neck pain, examiners of any level of experience, measures repeated at least twice, and statistical indexes on reliability. A device was considered inexpensive if it cost less than €500. The risk of bias of included studies was assessed by Quality Appraisal of Reliability Studies. RESULTS: The search yielded 35 151 records. Nine studies met all eligibility criteria. Their Quality Appraisal of Reliability Studies mean score was 3.7 of 11. No significant effect of the type of device (inexpensive vs expensive) on intraclass correlation coefficient (ICC) was identified for intrarater (ICC = 0.93 vs 0.91; P > .99) and inter-rater reliability (ICC = 0.80 vs 0.87; P > .99). The plane of movement did not affect inter-rater reliability (P = .11). Significant influences were identified with intrarater reliability (P = .0001) of inexpensive devices, where intrarater reliability decreased (P = .01) in side bending, compared with flexion-extension. CONCLUSIONS: The use of expensive devices to measure ACROM in adults with nonspecific neck pain does not seem to improve the reliability of the assessment. Side bending had a lower level of intrarater reliability.

Immediate versus delayed loading: comparison of primary stability loss after miniscrew placement in orthodontic patients-a single-centre blinded randomized clinical trial.

INTRODUCTION: The aim of this randomized clinical trial was to compare torque recordings at insertion time and 1 week post-placement between immediately loaded orthodontic miniscrews and an unloaded control group. TRIAL DESIGN: This RCT was designed as parallel with an allocation ratio of 1:1. METHODS: Eligibility criteria to enroll patients were: needs of fixed orthodontic treatment, no systemic disease, absence of using drugs altering bone metabolism. All patients were consecutively treated in a private practice and the miniscrews were placed by the same author. Patients received ORTHOImplant (3M Unitek) miniscrews and they were blindly divided in two groups: group 1 screws were unloaded between T0 and T1, group 2 received immediately loaded screws with NiTi coil. For each patient, maximum insertion torque (MIT) was evaluated at T0. After 1 week, without loading, the screw torque was measured again (T1) and at the end of the treatment maximal removal torque was evaluated (T2). Torque variation in the first week was considered as the primary outcome. RANDOMIZATION: A randomization list was created for the group assignment, with an allocation ratio of 1:1. BLINDING: The study was single blinded in regard of the statistical analysis. RESULTS: Patients enrolled in the clinical trial were 51 for a total of 81 miniscrews. The recruitment started in November 2012 and the observation period ended in August 2014. Twenty-six and twenty-five patients were analysed in group 1 and 2, respectively. The MIT mean in each placement time was 18.25 Ncm (SD = 3.00), 11.41 Ncm (SD = 3.51) and 10.52 Ncm (SD = 5.14) at T0, T1, and T2 time, respectively. In group 1, the torque decrease between T1 and T0 was statistically higher compared to group 2 (P value = 0.003). Statistically significant effects of the placement times on MIT were found (P value <0.0001). No serious harm was observed. LIMITATIONS: This study was performed using only direct force on the miniscrew and not using the miniscrew as an indirect anchorage. It was not possible to obtain quantitative data on bone quality or root proximity to miniscrews. CONCLUSIONS: A significant stability loss was observed in the first week in both groups; Group 1 showed a statistically higher torque loss in the first week when compared to the immediately loaded group. There were statistically significant effects of the measurement times on MIT and of the miniscrew location on MIT. The overall failure rate was 7.4%. TRIAL REGISTRATION: This trial was not registered. PROTOCOL: The protocol was not published before trial commencement.

Age-dependent accumulation of genomic aberrations and deregulation of cell cycle and telomerase genes in metastatic neuroblastoma.

About 50% of children with neuroblastoma (NB) show a metastatic disease and have a poor prognosis. However, disease progression is greatly variable and depends on patients' age and MYCN oncogene amplification. To investigate the role of patients' age in tumor aggressiveness, we performed array-CGH and gene expression profiles of three groups (G) of metastatic NBs: G1, stage 4S patients and MYCN single copy (MYCN-) tumors; G2, stage 4 patients, ≤ 18 months of age, MYCN- tumors and favorable outcome and G3, Stage 4 patients, ≥ 19 months with unfavorable outcome. G1 was characterized by numerical aberrations prevalently; on the contrary, all G3 tumors had structural rearrangements, whereas G2 showed an intermediate pattern. The average of numerical alterations decreased significantly from G1 to G2 to G3 (p < 0.01). Contrarily, the number of structural aberrations increased from G1 to G2 to G3 (p < 2.35 E-05). Noteworthy, G3/MYCN- NBs were characterized by several complex intrachromosome rearrangements. Expression analysis of the three groups showed significant differences in genes of Rho and Ras signaling pathways, development and adhesion, cell cycle regulation and telomerase activity. Accumulation of structural alterations increased with patients' age and was associated with a more aggressive disease. Abnormal expression of genes involved in cell cycle and telomerase in G3 may be responsible for the genomic instability in this cohort of patients. The higher DNA instability observed in G3/MYCN- NBs than in MYCN-amplified G3 may also explain why patients ≥ 19 months have a poor outcome independently by MYCN status.

Bone marrow of neuroblastoma patients shows downregulation of CXCL12 expression and presence of IFN signature.

BACKGROUND: At diagnosis, children with neuroblastoma (NB) present with either localized or metastatic disease. Since the mechanisms responsible for BM invasion are not well known, we investigated the transcriptome of resident BM cells from NB patients as compared to healthy children. PROCEDURE: Ninety-two and 88 children with localized and metastatic NB, respectively, and 15 healthy children were included in the study. BM resident cells recovered from BM aspirates by immunomagnetic bead manipulation were subjected to genome-wide microarray analysis. After validation in an independent set of samples, the genes significantly modulated in resident BM cells from NB patients were tested for their diagnostic/prognostic values. RESULTS: BM resident cells, irrespective of neoplastic cell invasion, significantly overexpressed genes involved in innate immune responses, and interferon (IFN) and IFN-DRS signatures were enriched. Genes coding for metallothioneins and zinc finger proteins, and involved in histone and nucleosome/chromatin organization were also overexpressed. Resident BM cells from NB patients significantly downregulated genes involved in cell adhesion, and in erythrocyte, myeloid, and platelet differentiation pathways. Among downregulated genes, CXCL12 expression reached near complete silencing in patients with metastatic disease. The downregulation of CXCL12 expression was independent of contact between NB cell and resident BM cell. CONCLUSIONS: We demonstrated that NB tumor growth at the primary site can alter the BM microenvironment, and the presence of BM-infiltrating NB cells makes the alterations more pronounced. Therefore, the restoration of a BM physiological state by means of IFN-α monoclonal antibody, Sifalimumab, and selective noradrenaline receptor blockers should be further studied to ameliorate patients' clinical management.

Study design and statistical analysis of data in human population studies with the micronucleus assay.

The most common study design performed in population studies based on the micronucleus (MN) assay, is the cross-sectional study, which is largely performed to evaluate the DNA damaging effects of exposure to genotoxic agents in the workplace, in the environment, as well as from diet or lifestyle factors. Sample size is still a critical issue in the design of MN studies since most recent studies considering gene-environment interaction, often require a sample size of several hundred subjects, which is in many cases difficult to achieve. The control of confounding is another major threat to the validity of causal inference. The most popular confounders considered in population studies using MN are age, gender and smoking habit. Extensive attention is given to the assessment of effect modification, given the increasing inclusion of biomarkers of genetic susceptibility in the study design. Selected issues concerning the statistical treatment of data have been addressed in this mini-review, starting from data description, which is a critical step of statistical analysis, since it allows to detect possible errors in the dataset to be analysed and to check the validity of assumptions required for more complex analyses. Basic issues dealing with statistical analysis of biomarkers are extensively evaluated, including methods to explore the dose-response relationship among two continuous variables and inferential analysis. A critical approach to the use of parametric and non-parametric methods is presented, before addressing the issue of most suitable multivariate models to fit MN data. In the last decade, the quality of statistical analysis of MN data has certainly evolved, although even nowadays only a small number of studies apply the Poisson model, which is the most suitable method for the analysis of MN data.

Identification and quantification of selected inflammatory genes modulated by leflunomide and prednisone treatment in early rheumatoid arthritis patients.

OBJECTIVES: The present study evaluates the effects of combined leflunomide (LEF) and low dose of prednisone therapy, on selected inflammatory gene expression in peripheral blood mononuclear cells (PBMCs) of early rheumatoid arthritis (ERA) patients by gene microarray analysis and quantitative real time-polymerase chain reaction (qRT-PCR). METHODS: Ten ERA patients (mean age 53 ± 10 years) were assigned as untreated (group 1) or pre-treated (group 2) with prednisone (5 mg/day for 3 months) after informed consent and ethics committee approval. Five sex- and age-matched healthy subjects were used as controls (CNT). RNA was extracted by PBMCs, amplified, labelled and hybridised on inflammation DualChip microarray. The expression ratio of 282 inflammatory genes between CNT and ERA patients, before (T0) and after 12 weeks (T1) of combined therapy was detected. qRT-PCR was performed on 7 selected inflammatory RA-related genes (STAT4, MAPK9, HIF1A, MIF, STAT6, NFKB1, TNFRSF1B). RESULTS: At T0, microarray analysis showed 34 altered genes in both ERA groups when compared to CNT (vs. CNT). Seven RA-related genes, investigated in further details, were found up-regulated in group 1 and down-regulated or unchanged in group 2 vs. CNT. At T1, combined therapy induced the down-regulation of these genes in both groups vs. CNT as also confirmed by qRT-PCR performed on selected genes. CONCLUSIONS: Untreated ERA patients seem characterised by up-regulation of specific genes involved both in the resistance/inhibition to apoptosis and in the stimulation of pro-inflammatory cytokine production by immune inflammatory cells. Combined LEF and low dose of prednisone therapy seems to play synergistic effects on down-regulation of these genes.