Telehealth mitigates COPD disease progression compared to standard of care: a randomized controlled crossover trial.

BACKGROUND: We showed excellent adherence and satisfaction with our telehealth care (TC) approach for COPD. Here, the results of a consecutive randomized controlled trial are presented. METHODS: Patients were randomly assigned to TC or standard care (SC). During TC, patients answered six daily questions online, and focused on the early recognition of exacerbations, in addition to SC. RESULTS: The mean increase in COPD assessment test (CAT) was 1.8 vs. 3.6 points/year in the TC and SC groups, respectively (P = 0.0015). Satisfaction with care (VAS) at baseline was 8.2; at the end of SC, 8.5 (P = 0.062); and after TC, 8.8 (P < 0.001). We detected significantly more moderate exacerbations during TC. CONCLUSION: Whilst receiving TC, the slope of the CAT increase - an indicator of the naturally progressive course of COPD - was reduced by 50%. Satisfaction with care increased with TC. The higher number of detected moderate exacerbations probably indicates a higher diagnostic sensitivity than without TC.

VEGFA variants are associated with pre-school lung function, but not neonatal lung function.

BACKGROUND: Vascular endothelial growth factor (VEGF) is implicated in airway remodelling and asthma development. We studied VEGFA gene variants and plasma levels and the development of lung function, bronchial hyperresponsiveness and asthma in childhood. METHODS: We analysed 13 SNPs in the VEGFA gene in 411 children from the COPSAC2000 high-risk birth cohort. Asthma was diagnosed prospectively, and lung function measurements were obtained at birth and 6 years of age. Plasma VEGF levels were measured at 18 months of age. We used a Bonferroni adjusted significance level. Findings were replicated in the Prevention and Incidence of Asthma and Mite Allergy (PIAMA) birth cohort at age 8. RESULTS: At age six, three SNPs from the same linkage block were associated with FEV1 (rs699947, P = 1.31E-05), independent of asthma, and there were suggestive associations between FEV1/FVC ratio and rs833052 and maximal mid-expiratory flow and rs6900017. Replication in the PIAMA cohort showed borderline association between FEV1 and rs699947 and significant meta-analysis result. SNPs upstream and nearby rs699947 were nominally associated with VEGF plasma levels. VEGF levels were not associated with asthmatic symptoms or lung function measures. CONCLUSIONS AND CLINICAL RELEVANCE: VEGF gene variants are associated with lung function at school age, but not at birth, suggesting a role of VEGF in post-natal lung function development.

Prevalence of sarcoidosis in Switzerland is associated with environmental factors.

The current study aimed to investigate incidence, prevalence and regional distribution of sarcoidosis in Switzerland with respect to environmental exposures. All sarcoidosis patients hospitalised between 2002 and 2005 were identified from the Swiss hospital statistics from the Swiss Federal Office for Statistics (Neuchâtel, Switzerland). Regional exposure characteristics included the regional distribution of different industrial sectors, agriculture and air quality. Co-inertia analysis, as well as a generalised linear model, was applied. The prevalence of "ever-in-life" diagnosed sarcoidosis, currently active sarcoidosis and sarcoidosis requiring hospitalisation was 121 (95% CI 93-149), 44 (95% CI 34-54) and 16 (95% CI 10-22) per 100,000 inhabitants, respectively. The mean annual incidence of sarcoidosis was 7 (95% CI 5-11) per 100,000 inhabitants. The regional workforce in the metal industry, water supply, air transport factories and the area of potato production, artificial meadows (grassland) and bread grains were positively associated with the frequency of sarcoidosis. The prevalence of sarcoidosis was higher than assumed based on former international estimates. Higher frequency was found in regions with metal industry and intense agriculture, especially production of potatoes, bread grains and artificial meadows.

Combined airway and oesophageal stenting in malignant airway-oesophageal fistulas: a prospective study.

Malignant airway-oesophageal fistulas (AEF) are a serious complication of advance oesophageal or lung cancer. The aim of this study was to assess the quality of life before and after stent insertion, and to examine the role of treatment and location of AEF as factors influencing survival in AEF patients managed with airway and/or oesophageal stent insertion. 112 patients with AEF were included prospectively. 83 (74%) patients had advanced lung cancer and 29 (26%) patients had oesophageal cancers. Airway stents were inserted in 65 (58%) patients, oesophageal stents in 37 (33%) patients, and both airway and oesophageal stents in 10 (9%) patients. Seven (6%) patients developed respiratory failure and required transient ventilator support in the intensive care unit (four patients with airway stenting, two patients with double stents and one patient in the oesophageal stenting group). None of the patients developed stent migration or needed stent repositioning. Overall, mean survival was 236.6 days (airway stent 219.1 days, oesophageal stent 262.8 days and combined airway-oesophageal stent 252.9 days). Backward, stepwise regression revealed the site of stent placement (airway and/or oesophagus; p < 0.028), exact location of the fistula in airway (p = 0.011) and additional treatment with chemotherapy and/or radiation (p < 0.001) as independent risk factors predicting increased survival. The mean quality of life score (QoL) was 81 prior to stent insertion and 72 post-stent insertion (p < 0.001). Airway and/or oesophageal stent insertion provides an effective approach to improve the QoL in patients with malignant AEF.

Length of hospital stay for TB varies with comorbidity and hospital location.

BACKGROUND: Although most guidelines overwhelmingly recommend outpatient TB treatment, hospitalisations are common. We investigated the proportion of TB patients hospitalised and determined factors associated with length of stay (LOS) in Switzerland.METHODS: Cases with TB as the primary diagnosis were retrieved from a nation-wide hospitalisation database and compared to TB notifications. Month and year of admission, hospital site, type of TB, age, sex, LOS and up to 50 ICD-10 coded comorbidities were compared with controls matched for age, sex and admission date.RESULTS: From 2002 to 2015, the estimated TB hospitalisation rate was 81%. The median LOS of 6,234 TB patients was stable at 14 days (IQR 6-22), but increased in patients with miliary TB, old patients and with hospital location. TB-associated comorbidities included HIV, liver disease, anaemia, malnutrition and genitourinary tract diseases. LOS was associated with three comorbidity clusters: 1) malnutrition, cachexia and anaemia (median LOS 20 days, IQR 13-31); 2) toxic liver disease and hepatitis (median LOS 23 days, IQR 14-37.5); and 3) adverse drug events (median LOS 20 days, IQR 13-30).CONCLUSION: Most TB patients were hospitalised. LOS was related to TB type, comorbidities and hospital location. Promoting outpatient care is a priority to improve TB management in Switzerland.

Erlotinib has comparable clinical efficacy to chemotherapy in pretreated patients with advanced non-small cell lung cancer (NSCLC): A propensity-adjusted, outcomes research-based study.

OBJECTIVES: Controversy exists about the integration of erlotinib in patients with EGFR wildtype, advanced NSCLC. MATERIALS AND METHODS: We included patients with advanced NSCLC receiving at least two lines of palliative systemic treatment between January 2005 and December 2014 and not harbouring targetable driver mutations. Primary study endpoint was overall survival (OS), secondary endpoint progression-free survival (PFS). We used Kaplan-Meier statistics, multivariate Cox regression and Propensity score or Inverse Probability Weights (IPW) matching to compare clinical outcome between patients receiving erlotinib in second or further line and those receiving chemotherapy only. The study had a power of 90% to detect a survival superiority of 30%. RESULTS: From a total of 827 patients, we excluded 171 patients with potentially curative treatment, 189 receiving treatment outside of our institute, 206 receiving no or only one line of systemic treatment, 6 with ALK translocations and 28 with EGFR mutations. From 227 patients in the final efficacy analysis, 125 patients received erlotinib in second (89 patients), third (28) or further-line (8), and 102 patients received chemotherapy only. Women and never smokers were significantly overrepresented in the erlotinib group. Both OS (hazard ratio (HR)=1.14, 95% CI 0.80-1.63, P=0.448) and PFS (HR=1.20, 95% CI 0.95-1.52, P=0.119) were similar in the erlotinib compared to the chemotherapy group using IPW-adjusted Cox regression analysis treating the use of erlotinib as a time-dependent covariate starting from second-line treatment and stratified for ECOG performance status and treatment line. ECOG performance status was the most powerful covariate to select patients for erlotinib treatment. CONCLUSION: The present study suggests erlotinib to have similar clinical efficacy compared to chemotherapy in patients with pretreated advanced NSCLC and no known molecular targetable alterations.

Modelling the effect of a temperature shift on the lag phase duration of Listeria monocytogenes.

The aim of this work is to study and model the effect of a temperature shift on h(0), the product of the growth rate by the lag phase duration (mulambda). Our work is based on the data of Whiting and Bagi [Int. J. Food Microbiol. 73 (2002) 291], who studied the influence of both the pre-incubation temperature (T(prior)) and the growth temperature (T(growth)) on lambda values of Listeria monocytogenes. We introduce a new model to describe the evolution of the parameter h(0) as a function of T(prior) and T(growth), and compare it to Whiting and Bagi's published polynomial model that describes the influence of T(prior) and T(growth) on lambda independently of mu. For exponential as well as stationary phase cells, h(0) increases almost linearly with the magnitude of the temperature shift. A simple linear model of h(0) turns out to be more suitable to predict lambda values than a polynomial model of lambda.

A comparison of anxiety treatments with adults who have moderate and severe mental retardation.

Several authors have suggested that Abbreviated Progressive Relaxation may not be effective with clients who have moderate and severe mental retardation. Because of this the authors were interested in the development of behavioural relaxation which is a more simple technique and does not require a conceptual awareness of internal states of tension. These two treatments were compared in group and individual forms with four groups of subjects. Subjects were assessed using measures of rated anxiety and pulse rate before, during, and after treatment. The rated anxiety measures suggest Behavioural Relaxation Training is more effective than Abbreviated Progressive Relaxation in both group and individual formats. There were no significant differences on the pulse rate measures.

Circulating microRNA profiling in patients with advanced non-squamous NSCLC receiving bevacizumab/erlotinib followed by platinum-based chemotherapy at progression (SAKK 19/05).

OBJECTIVES: Molecular subclassification of non small-cell lung cancer (NSCLC) is essential to improve clinical outcome. This study assessed the prognostic and predictive value of circulating micro-RNA (miRNA) in patients with non-squamous NSCLC enrolled in the phase II SAKK (Swiss Group for Clinical Cancer Research) trial 19/05, receiving uniform treatment with first-line bevacizumab and erlotinib followed by platinum-based chemotherapy at progression. MATERIALS AND METHODS: Fifty patients with baseline and 24 h blood samples were included from SAKK 19/05. The primary study endpoint was to identify prognostic (overall survival, OS) miRNA's. Patient samples were analyzed with Agilent human miRNA 8x60K microarrays, each glass slide formatted with eight high-definition 60K arrays. Each array contained 40 probes targeting each of the 1347 miRNA. Data preprocessing included quantile normalization using robust multi-array average (RMA) algorithm. Prognostic and predictive miRNA expression profiles were identified by Spearman's rank correlation test (percentage tumor shrinkage) or log-rank testing (for time-to-event endpoints). RESULTS: Data preprocessing kept 49 patients and 424 miRNA for further analysis. Ten miRNA's were significantly associated with OS, with hsa-miR-29a being the strongest prognostic marker (HR=6.44, 95%-CI 2.39-17.33). Patients with high has-miR-29a expression had a significantly lower survival at 10 months compared to patients with a low expression (54% versus 83%). Six out of the 10 miRNA's (hsa-miRN-29a, hsa-miR-542-5p, hsa-miR-502-3p, hsa-miR-376a, hsa-miR-500a, hsa-miR-424) were insensitive to perturbations according to jackknife cross-validation on their HR for OS. The respective principal component analysis (PCA) defined a meta-miRNA signature including the same 6 miRNA's, resulting in a HR of 0.66 (95%-CI 0.53-0.82). CONCLUSION: Cell-free circulating miRNA-profiling successfully identified a highly prognostic 6-gene signature in patients with advanced non-squamous NSCLC. Circulating miRNA profiling should further be validated in external cohorts for the selection and monitoring of systemic treatment in patients with advanced NSCLC.

Functional characterization of high levels of meningioma 1 as collaborating oncogene in acute leukemia.

Retroviral expression of leukemogenic oncogenes in the murine hematopoietic system is essential but not sufficient to induce acute leukemia. Proviral integration-mediated elevated expression of the meningioma 1 (MN1) oncogene suggested MN1 acting as cooperating event in mixed-lineage leukemia 1 (MLL) and eleven nineteen leukemia (ENL)-induced murine leukemia. Indeed, co-expression of MN1 with MLL-ENL enhanced transformation in vivo, and resulted in a significantly reduced latency for induction of an aggressive acute leukemia when compared with MN1 or MLL-ENL alone. In addition, co-expression of MN1 increased the granulocyte macrophage progenitor cell population with leukemia-initiating properties as shown in secondary transplantation experiments. Gene expression profiling experiments identified putative downstream MN1 targets, of which FMS-like tyrosine kinase 3 (FLT3) and CD34 were upregulated in both MN1-overexpressing murine leukemias and in pediatric acute leukemias with high MN1 levels. Interestingly, small interfering RNA (siRNA)-mediated MN1 knockdown resulted in cell cycle arrest and impaired clonogenic growth of human leukemia cell lines with high MN1 levels. Our work shows for the first time that high MN1 levels are important for the growth of leukemic cells, and that increased MN1 expression can synergize with MLL-ENL and probably other transforming fusion genes in leukemia induction through a distinct gene expression program that is able to expand the leukemia-initiating cell population.

Comprehensive epidermal growth factor receptor gene analysis from cytological specimens of non-small-cell lung cancers.

Epidermal growth factor receptor (EGFR) gene mutations and increased copy numbers are considered as predictors of response to EGFR tyrosine kinase inhibitors (EGFR-TKI) in non-small-cell lung cancer (NSCLC). Lung cancer diagnosis is often based on cytology alone. However, almost all published data on EGFR gene analyses were obtained from biopsies. This study tested the feasibility of EGFR gene analyses on cytological specimens. Eighty-four cytological specimens from NSCLCs were prospectively analysed for EGFR gene mutation in exons 18-21 and EGFR gene copy numbers were evaluated by fluorescence in situ hybridisation (FISH). A FISH-positive result was defined according to the criteria by Cappuzzo et al established for biopsies of NSCLCs. Fluorescence in situ hybridisation results of cytological specimens were compared to the FISH results on matching biopsies (n=33). Initial diagnosis of NSCLC was solely based on cytology in 37 out of 84 (44.0%) patients. Out of 80 NSCLCs, 6 (7.5%) showed EGFR gene mutations. Out of 67 cancers, 45 (67.2%) were FISH positive on cytological specimens. Comparison of FISH showed a FISH-positive result in 21 out of 33 (63.6%) cytological specimens but in only 8 out of 33 (24.2%) matched biopsies. Epidermal growth factor receptor gene analyses are well applicable to cytological specimens. The high FISH-positive rate of NSCLC on cytological specimens contrasts with the low rate on biopsies when previously suggested criteria are used. New criteria for a positive EGFR FISH status to predict response to therapy with EGFR-TKI need to be defined for cytological specimens.

BIBI, a bioinformatics bacterial identification tool.

BIBI was designed to automate DNA sequence analysis for bacterial identification in the clinical field. BIBI relies on the use of BLAST and CLUSTAL W programs applied to different subsets of sequences extracted from GenBank. These sequences are filtered and stored in a new database, which is adapted to bacterial identification.

Modeling the lag time of Listeria monocytogenes from viable count enumeration and optical density data.

The following two factors significantly influence estimates of the maximum specific growth rate ( micro (max)) and the lag-phase duration (lambda): (i) the technique used to monitor bacterial growth and (ii) the model fitted to estimate parameters. In this study, nine strains of Listeria monocytogenes were monitored simultaneously by optical density (OD) analysis and by viable count enumeration (VCE) analysis. Four usual growth models were fitted to our data, and estimates of growth parameters were compared from one model to another and from one monitoring technique to another. Our results show that growth parameter estimates depended on the model used to fit data, whereas there were no systematic variations in the estimates of micro (max) and lambda when the estimates were based on OD data instead of VCE data. By studying the evolution of OD and VCE simultaneously, we found that while log OD/VCE remained constant for some of our experiments, a visible linear increase occurred during the lag phase for other experiments. We developed a global model that fits both OD and VCE data. This model enabled us to detect for some of our strains an increase in OD during the lag phase. If not taken into account, this phenomenon may lead to an underestimate of lambda.

Teaching mentally handicapped adults how to use a cafeteria.

This study taught three moderately to severely mentally handicapped women skills to enable them to make use of cafeterias. While some work has been carried out in this area (e.g. Marholin et al., 1979; Van den Pol et al., 1981; Desai, 1983), it has not established whether hospital-based individuals with this level of handicap and no previous experience of cafeterias can be taught how to use them. A role-playing procedure was used during training with in vivo assessments being carried out before and after training. An in vivo generalization assessment was also conducted. Training was found to be successful with the skills taught transferring to the real life situation and subjects' improved performance, in the majority of the skill areas, generalizing to a 'new' cafeteria which had a completely different system of use.

The consistency of reports about feelings and emotions from people with intellectual disability.

Sixty-seven subjects with mild or moderate intellectual disability were assessed on a variety of measures of emotion. All of the measures were self-report measures and all of the data is based on reports by the subjects' themselves. The battery included the Zung Self-Rating Anxiety Scale, the Zung Depression Inventory, the General Health Questionnaire and the Eysenck-Withers Personality Test. The results reveal an impressive amount of convergent validity in the subjects' emotional systems.