Genotypic classification of patients with Wolfram syndrome: insights into the natural history of the disease and correlation with phenotype

Purpose: Wolfram syndrome is a degenerative, recessive rare disease with an onset in childhood. It is caused by mutations in WFS1 or CISD2 genes. More than 200 different variations in WFS1 have been described in patients with Wolfram syndrome, which complicates the establishment of clear genotype-phenotype correlation. The purpose of this study was to elucidate the role of WFS1 mutations and update the natural history of the disease. Methods: This study analyzed clinical and genetic data of 412 patients with Wolfram syndrome published in the last 15 years. Results: (i) 15% of published patients do not fulfill the current ­inclusion criterion; (ii) genotypic prevalence differences may exist among countries; (iii) diabetes mellitus and optic atrophy might not be the first two clinical features in some patients; (iv) mutations are nonuniformly distributed in WFS1; (v) age at onset of diabetes mellitus, hearing defects, and diabetes insipidus may depend on the patient"s genotypic class; and (vi) disease progression rate might depend on genotypic class. Conclusion: New genotype-phenotype correlations were established, disease progression rate for the general population and for the genotypic classes has been calculated, and new diagnostic criteria have been proposed. The conclusions raised could be important for patient management and counseling as well as for the development of treatments for Wolfram syndrome.

Prospective multicenter international surveillance of azole resistance in Aspergillus fumigatus.

To investigate azole resistance in clinical Aspergillus isolates, we conducted prospective multicenter international surveillance. A total of 3,788 Aspergillus isolates were screened in 22 centers from 19 countries. Azole-resistant A. fumigatus was more frequently found (3.2% prevalence) than previously acknowledged, causing resistant invasive and noninvasive aspergillosis and severely compromising clinical use of azoles.

May increasing incidence of breast cancer be related to overdiagnosis? : a population-based study

Background: Breast cancer is the first cause of cancer in women in Switzerland. While breast cancer mortality has sharply decreased in the two last decades in Switzerland, the incidence of breast cancer has increased during the same period. Various reasons for this increase have been hypothesized, such as the increase in the prevalence of obesity, the use of postmenauposal hormone replacement therapy, or a later age for having a first child. Overdiagnosis secondary to screening and any other forms of early detection procedures could be also involved. Analyses of breast cancer by stage can help evaluate if overdiagnosis could have contributed to the increase in the incidence of breast cancer. Methods: We used data from the Valais cancer registry at the Observatoire valaisan de la santé (www.ovs.ch). This population based registry collects data on all new (incident) cases of cancer diagnosed in women living in one canton of Switzerland, Valais. Cancers are coded according to the International Classification of Diseases for Oncology (ICD-O-3) and the stages are coded according to the TNM classification. Information on breast cancer stage (in situ: 0; invasive: I, II, III, IV) was available for all cases recorded between 1993 and 2011 (N=4246). Standardized rates of breast cancer were computed (direct standardization on European population).

Disease profiles of detainees in the Canton of Vaud in Switzerland: gender and age differences in substance abuse, mental health and chronic health conditions.

BACKGROUND: Literature on the disease profile of prisoners that differentiates by age and gender remains sparse. This study aimed to describe the health of correctional inmates in terms of substance abuse problems and mental and somatic health conditions, and compare it by gender and age. METHODS: This study examined cross-sectional data from the Canton of Vaud in Switzerland on the health conditions of detainees who were in prison on January 1, 2011 or entered prison in 2011. Health conditions validated by physician examination were reported using the International Classification of Diseases (ICD) version 10. The analyses were descriptive by groups of prisoners: the entire sample (All), Men, Older adults and Women. RESULTS: A total of 1,664 individuals were included in the analysis. Men comprised 91.5 % of the sample and had a mean age of 33 years. The other 8.5 % were women and had an average age of 39. Older adults (i.e., age 50 and older) represented 7 % of the total sample. Overall, 80 % of inmates were non-Swiss citizens, but the proportion of Swiss prisoners was higher among the older adults (51 %) and women (29 %). Overall, 41 % of inmates self-reported substance abuse problems. Of those, 27 % were being treated by psychiatrists for behavioral disorders related to substance abuse. Chronic infectious diseases were found in 9 % of the prison population. In addition, 27 % of detainees suffered from serious mental health conditions. Gender and age had an influence on the disease profile of this sample: compared to the entire prison population, the older inmates were less likely to misuse illegal drugs and to suffer from communicable infections but exhibited more problems with alcohol and a higher burden of chronic health conditions. Female prisoners were more disposed to mental health problems (including drug abuse) and infectious diseases. In terms of chronic diseases, women suffered from the same conditions as men, but the diseases were more prevalent in women. CONCLUSION: It is important to understand the different disease profiles of prisoners by gender and age, as it helps identify the needs of different groups and tailor age-and gender-specific interventions.

Preoperative assessment and classification of benign laryngotracheal stenosis: a consensus paper of the European Laryngological Society.

Adult and pediatric laryngotracheal stenoses (LTS) comprise a wide array of various conditions that require precise preoperative assessment and classification to improve comparison of different therapeutic modalities in a matched series of patients. This consensus paper of the European Laryngological Society proposes a five-step endoscopic airway assessment and a standardized reporting system to better differentiate fresh, incipient from mature, cicatricial LTSs, simple one-level from complex multilevel LTSs and finally "healthy" from "severely morbid" patients. The proposed scoring system, which integrates all of these parameters, may be used to help define different groups of LTS patients, choose the best treatment modality for each individual patient and assess distinct post-treatment outcomes accordingly.

Clustering and International Competitiveness of Information Technology Industry in the Saint Petersburg Area

The main objective of this study is to assess the potential of the information technology industry in the Saint Petersburg area to become one of the new key industries in the Russian economy. To achieve this objective, the study analyzes especially the international competitiveness of the industry and the conditions for clustering. Russia is currently heavily dependent on its natural resources, which are the main source of its recent economic growth. In order to achieve good long-term economic performance, Russia needs diversification in its well-performing industries in addition to the ones operating in the field of natural resources. The Russian government has acknowledged this and started special initiatives to promote such other industries as information technology and nanotechnology. An interesting industry that is basically less than 20 years old and fast growing in Russia, is information technology. Information technology activities and markets are mainly concentrated in Russia’s two biggest cities, Moscow and Saint Petersburg, and areas around them. The information technology industry in the Saint Petersburg area, although smaller than Moscow, is especially dynamic and is gaining increasing foreign company presence. However, the industry is not yet internationally competitive as it lacks substantial and sustainable competitive advantages. The industry is also merely a potential global information technology cluster, as it lacks the competitive edge and a wide supplier and manufacturing base and other related parts of the whole information technology value system. Alone, the industry will not become a key industry in Russia, but it will, on the other hand, have an important supporting role for the development of other industries. The information technology market in the Saint Petersburg area is already large and if more tightly integrated to Moscow, they will together form a huge and still growing market sufficient for most companies operating in Russia currently and in the future. Therefore, the potential of information technology inside Russia is immense.

Impact of early valve surgery on outcome of Staphylococcus aureus prosthetic valve infective endocarditis: analysis in the International Collaboration of Endocarditis-Prospective Cohort Study.

BACKGROUND: The impact of early valve surgery (EVS) on the outcome of Staphylococcus aureus (SA) prosthetic valve infective endocarditis (PVIE) is unresolved. The objective of this study was to evaluate the association between EVS, performed within the first 60 days of hospitalization, and outcome of SA PVIE within the International Collaboration on Endocarditis-Prospective Cohort Study. METHODS: Participants were enrolled between June 2000 and December 2006. Cox proportional hazards modeling that included surgery as a time-dependent covariate and propensity adjustment for likelihood to receive cardiac surgery was used to evaluate the impact of EVS and 1-year all-cause mortality on patients with definite left-sided S. aureus PVIE and no history of injection drug use. RESULTS: EVS was performed in 74 of the 168 (44.3%) patients. One-year mortality was significantly higher among patients with S. aureus PVIE than in patients with non-S. aureus PVIE (48.2% vs 32.9%; P = .003). Staphylococcus aureus PVIE patients who underwent EVS had a significantly lower 1-year mortality rate (33.8% vs 59.1%; P = .001). In multivariate, propensity-adjusted models, EVS was not associated with 1-year mortality (risk ratio, 0.67 [95% confidence interval, .39-1.15]; P = .15). CONCLUSIONS: In this prospective, multinational cohort of patients with S. aureus PVIE, EVS was not associated with reduced 1-year mortality. The decision to pursue EVS should be individualized for each patient, based upon infection-specific characteristics rather than solely upon the microbiology of the infection causing PVIE.

Clustering and international competitiveness of information technology industry in the Saint Petersburg area

The main objective of this study is to assess the potential of the information technology industry in the Saint Petersburg area to become one of the new key industries in the Russian economy. To achieve this objective, the study analyzes especially the international competitiveness of the industry and the conditions for clustering. Russia is currently heavily dependent on its natural resources, which are the main source of its recent economic growth. In order to achieve good long-term economic performance, Russia needs diversification in its well-performing industries in addition to the ones operating in the field of natural resources. The Russian government has acknowledged this and started special initiatives to promote such other industries as information technology and nanotechnology. An interesting industry that is basically less than 20 years old and fast growing in Russia, is information technology. Information technology activities and markets are mainly concentrated in Russia’s two biggest cities, Moscow and Saint Petersburg, and areas around them. The information technology industry in the Saint Petersburg area, although smaller than Moscow, is especially dynamic and is gaining increasing foreign company presence. However, the industry is not yet internationally competitive as it lacks substantial and sustainable competitive advantages. The industry is also merely a potential global information technology cluster, as it lacks the competitive edge and a wide supplier and manufacturing base and other related parts of the whole information technology value system. Alone, the industry will not become a key industry in Russia, but it will, on the other hand, have an important supporting role for the development of other industries. The information technology market in the Saint Petersburg area is already large and if more tightly integrated to Moscow, they will together form a huge and still growing market sufficient for most companies operating in Russia currently and in the future. Therefore, the potential of information technology inside Russia is immense.

Bayesian Networks for the Age Classification of Living Individuals: a Study on Transition Analysis

Over the past few decades, age estimation of living persons has represented a challenging task for many forensic services worldwide. In general, the process for age estimation includes the observation of the degree of maturity reached by some physical attributes, such as dentition or several ossification centers. The estimated chronological age or the probability that an individual belongs to a meaningful class of ages is then obtained from the observed degree of maturity by means of various statistical methods. Among these methods, those developed in a Bayesian framework offer to users the possibility of coherently dealing with the uncertainty associated with age estimation and of assessing in a transparent and logical way the probability that an examined individual is younger or older than a given age threshold. Recently, a Bayesian network for age estimation has been presented in scientific literature; this kind of probabilistic graphical tool may facilitate the use of the probabilistic approach. Probabilities of interest in the network are assigned by means of transition analysis, a statistical parametric model, which links the chronological age and the degree of maturity by means of specific regression models, such as logit or probit models. Since different regression models can be employed in transition analysis, the aim of this paper is to study the influence of the model in the classification of individuals. The analysis was performed using a dataset related to the ossifications status of the medial clavicular epiphysis and results support that the classification of individuals is not dependent on the choice of the regression model.

Towards actionable international comparisons of health system performance: expert revision of the OECD framework and quality indicators.

OBJECTIVE: To review and update the conceptual framework, indicator content and research priorities of the Organisation for Economic Cooperation and Development's (OECD) Health Care Quality Indicators (HCQI) project, after a decade of collaborative work. DESIGN: A structured assessment was carried out using a modified Delphi approach, followed by a consensus meeting, to assess the suite of HCQI for international comparisons, agree on revisions to the original framework and set priorities for research and development. SETTING: International group of countries participating to OECD projects. PARTICIPANTS: Members of the OECD HCQI expert group. RESULTS: A reference matrix, based on a revised performance framework, was used to map and assess all seventy HCQI routinely calculated by the OECD expert group. A total of 21 indicators were agreed to be excluded, due to the following concerns: (i) relevance, (ii) international comparability, particularly where heterogeneous coding practices might induce bias, (iii) feasibility, when the number of countries able to report was limited and the added value did not justify sustained effort and (iv) actionability, for indicators that were unlikely to improve on the basis of targeted policy interventions. CONCLUSIONS: The revised OECD framework for HCQI represents a new milestone of a long-standing international collaboration among a group of countries committed to building common ground for performance measurement. The expert group believes that the continuation of this work is paramount to provide decision makers with a validated toolbox to directly act on quality improvement strategies.

Prevalence of sleep apnoea syndrome in the middle to old age general population.

On the basis of a large populationbased sample who underwent full polysomnography at home (HypnoLaus cohort), we recently reported that 49·7% of men and 23·4% of women aged 40 years or older had an apnoea-hypopnoea index of 15 events per h or more1 according to the American Academy of Sleep Medicine (AASM) 2013 scoring criteria. When excessive daytime sleepiness (ie, Epworth score >10 [maximum score 24]) was included in the definition with an apnoea-hypopnoea index of 5 events per h or more, the prevalence was 12·5% in men and 5·9% in women. This high prevalence of sleep disordered breathing reinforced the idea that the treatment decision should not only be based the apnoeahypopnoea index, but should also take into account associated symptoms and cardiovascular and metabolic comorbidities. After this Article was published, several readers contacted us to ask for the prevalence of sleep apnoea syndrome in our sample according to the International Classification of Sleep Disorders (ICSD-3) criteria. These criteria include either the presence of an apnoea-hypopnoea index of 5 events per h or more associated with obstructive sleep apnoearelated symptoms or cardiovascular and metabolic comorbidities, or an apnoea-hypopnoea index of 15 events per h or more (figure).

International comparison of the German evidence-based S3-guidelines on the diagnosis and multimodal treatment of early and locally advanced gastric cancer, including adenocarcinoma of the lower esophagus.

BACKGROUND: Clinical guidelines are essential in implementing and maintaining nationwide stage-specific diagnostic and therapeutic standards. In 2011, the first German expert consensus guideline defined the evidence for diagnosis and treatment of early and locally advanced esophagogastric cancers. Here, we compare this guideline with other national guidelines as well as current literature. METHODS: The German S3-guideline used an approved development process with de novo literature research, international guideline adaptation, or good clinical practice. Other recent evidence-based national guidelines and current references were compared with German recommendations. RESULTS: In the German S3 and other Western guidelines, adenocarcinomas of the esophagogastric junction (AEG) are classified according to formerly defined AEG I-III subgroups due to the high surgical impact. To stage local disease, computed tomography of the chest and abdomen and endosonography are reinforced. In contrast, laparoscopy is optional for staging. Mucosal cancers (T1a) should be endoscopically resected "en-bloc" to allow complete histological evaluation of lateral and basal margins. For locally advanced cancers of the stomach or esophagogastric junction (≥T3N+), preferred treatment is preoperative and postoperative chemotherapy. Preoperative radiochemotherapy is an evidence-based alternative for large AEG type I-II tumors (≥T3N+). Additionally, some experts recommend treating T2 tumors with a similar approach, mainly because pretherapeutic staging is often considered to be unreliable. CONCLUSIONS: The German S3 guideline represents an up-to-date European position with regard to diagnosis, staging, and treatment recommendations for patients with locally advanced esophagogastric cancer. Effects of perioperative chemotherapy versus chemoradiotherapy are still to be investigated for adenocarcinoma of the cardia and the lower esophagus.

Performance of diagnostic centers in the classification of opportunistic screening mammograms from the Brazilian public health system (SUS)

Objective To evaluate the performance of diagnostic centers in the classification of mammography reports from an opportunistic screening undertaken by the Brazilian public health system (SUS) in the municipality of Goiânia, GO, Brazil in 2010. Materials and Methods The present ecological study analyzed data reported to the Sistema de Informação do Controle do Câncer de Mama (SISMAMA) (Breast Cancer Management Information System) by diagnostic centers involved in the mammographic screening developed by the SUS. Based on the frequency of mammograms per BI-RADS® category and on the limits established for the present study, the authors have calculated the rate of conformity for each diagnostic center. Diagnostic centers with equal rates of conformity were considered as having equal performance. Results Fifteen diagnostic centers performed mammographic studies for SUS and reported 31,198 screening mammograms. The performance of the diagnostic centers concerning BI-RADS classification has demonstrated that none of them was in conformity for all categories, one center presented conformity in five categories, two centers, in four categories, three centers, in three categories, two centers, in two categories, four centers, in one category, and three centers with no conformity. Conclusion The results of the present study demonstrate unevenness in the diagnostic centers performance in the classification of mammograms reported to SISMAMA from the opportunistic screening undertaken by SUS.

Classification of chronic obstructive pulmonary disease based on chest radiography

Objective Quantitative analysis of chest radiographs of patients with and without chronic obstructive pulmonary disease (COPD) determining if the data obtained from such radiographic images could classify such individuals according to the presence or absence of disease. Materials and Methods For such a purpose, three groups of chest radiographic images were utilized, namely: group 1, including 25 individuals with COPD; group 2, including 27 individuals without COPD; and group 3 (utilized for the reclassification /validation of the analysis), including 15 individuals with COPD. The COPD classification was based on spirometry. The variables normalized by retrosternal height were the following: pulmonary width (LARGP); levels of right (ALBDIR) and left (ALBESQ) diaphragmatic eventration; costophrenic angle (ANGCF); and right (DISDIR) and left (DISESQ) intercostal distances. Results As the radiographic images of patients with and without COPD were compared, statistically significant differences were observed between the two groups on the variables related to the diaphragm. In the COPD reclassification the following variables presented the highest indices of correct classification: ANGCF (80%), ALBDIR (73.3%), ALBESQ (86.7%). Conclusion The radiographic assessment of the chest demonstrated that the variables related to the diaphragm allow a better differentiation between individuals with and without COPD.