Paralyzed neonatal larynx in adduction. Case series, systematic review and analysis.

OBJECTIVE: Bilateral vocal cord abductor paralysis (BVCAbP) is considered a rare cause of stridor in the newborn. The goal of this work is to present a case series and to review systematically the literature on bilateral vocal cord abductor paralysis in the newborn to better characterize the current knowledge on this entity. METHODS: We performed a systematic literature review with Medline (1950-2011). The authors screened all cases of BVCAbP reported and selected those affecting newborns. RESULTS: Out of the 129 articles screened, 16 were included. A total of 69 cases could be retrieved and analyzed. Associated co-morbidities were found in 54% of the patients, most notably malformative conditions (intracranial or other), or a positive perinatal history (trauma/asphyxia, prematurity). Tracheostomy placement was required in 59% of children, and of these 44% were successfully decannulated. In terms of functional outcome full recovery or improvement were seen in 61% of patients. Major underlying co-morbidities affected negatively the functional outcome (p=.004), but not the need for tracheostomy (p=.604) or the decannulation success rate (p=.063). CONCLUSION: BVCAbP in the newborn is a serious cause of airway obstruction. It can be seen either in a context of multisystem anomalies or as an isolated finding. Newborns with major co-morbidities affecting their normal development are more likely to have poor functional outcomes and to remain tracheostomy-dependant.

Outcomes from studies of Antineutrophil Cytoplasm Antibody Associated Vasculitis: a systematic review by the European League Against Rheumatism systemic vasculitis task force.

Objectives: We undertook a systematic literature review as a background to the European League Against Rheumatism (EULAR) recommendations for conducting clinical trials in anti-neutrophil cytoplasm antibody associated vasculitis (AAV), and to assess the quality of evidence for outcome measures in AAV. Methods: Using a systematic Medline search, we categorised the identified studies according to diagnoses. Factors affecting remission, relapse, renal function and overall survival were identified. Results: A total of 44 papers were reviewed from 502 identified by our search criteria. There was considerable inconsistency in definitions of end points. Remission rates varied from 30% to 93% in Wegener granulomatosis (WG), 75% to 89% in microscopic polyangiitis (MPA) and 81% to 91% in Churg¿Strauss syndrome (CSS). The 5-year survival for WG, MPA and CSS was 74¿91%, 45¿76% and 60¿97%. Relapse (variably defined) was common in the first 2 years but the frequency varied: 18% to 60% in WG, 8% in MPA, and 35% in CSS. The rate of renal survival in WG varied from 23% at 15 months to 23% at 120 months. Methods used to assess morbidity varied between studies. Ignoring the variations in definitions of the stage of disease, factors influencing remission, relapse, renal and overall survival included immunosuppressive therapy used, type of organ involvement, presence of ANCA, older age and male ender. Conclusions: Factors influencing remission, relapse, renal and overall survival include the type of immunosuppressive therapy used, pattern of organ involvement, presence of ANCA, older age and male gender. Methodological variations between studies highlight the need for a consensus on terminology and definitions for future conduct of clinical studies in AAV.

Benchmarking therapeutic drug monitoring software: A systematic evaluation of available computer tools

Introduction: Therapeutic drug monitoring (TDM) aims at optimizing treatment by individualizing dosage regimen based on measurement of blood concentrations. Maintaining concentrations within a target range requires pharmacokinetic and clinical capabilities. Bayesian calculation represents a gold standard in TDM approach but requires computing assistance. In the last decades computer programs have been developed to assist clinicians in this assignment. The aim of this benchmarking was to assess and compare computer tools designed to support TDM clinical activities.¦Method: Literature and Internet search was performed to identify software. All programs were tested on common personal computer. Each program was scored against a standardized grid covering pharmacokinetic relevance, user-friendliness, computing aspects, interfacing, and storage. A weighting factor was applied to each criterion of the grid to consider its relative importance. To assess the robustness of the software, six representative clinical vignettes were also processed through all of them.¦Results: 12 software tools were identified, tested and ranked. It represents a comprehensive review of the available software's characteristics. Numbers of drugs handled vary widely and 8 programs offer the ability to the user to add its own drug model. 10 computer programs are able to compute Bayesian dosage adaptation based on a blood concentration (a posteriori adjustment) while 9 are also able to suggest a priori dosage regimen (prior to any blood concentration measurement), based on individual patient covariates, such as age, gender, weight. Among those applying Bayesian analysis, one uses the non-parametric approach. The top 2 software emerging from this benchmark are MwPharm and TCIWorks. Other programs evaluated have also a good potential but are less sophisticated (e.g. in terms of storage or report generation) or less user-friendly.¦Conclusion: Whereas 2 integrated programs are at the top of the ranked listed, such complex tools would possibly not fit all institutions, and each software tool must be regarded with respect to individual needs of hospitals or clinicians. Interest in computing tool to support therapeutic monitoring is still growing. Although developers put efforts into it the last years, there is still room for improvement, especially in terms of institutional information system interfacing, user-friendliness, capacity of data storage and report generation.

Clinical Disease Severity of Respiratory Viral Co-Infection versus Single Viral Infection: A Systematic Review and Meta-Analysis.

BACKGROUND: Results from cohort studies evaluating the severity of respiratory viral co-infections are conflicting. We conducted a systematic review and meta-analysis to assess the clinical severity of viral co-infections as compared to single viral respiratory infections. METHODS: We searched electronic databases and other sources for studies published up to January 28, 2013. We included observational studies on inpatients with respiratory illnesses comparing the clinical severity of viral co-infections to single viral infections as detected by molecular assays. The primary outcome reflecting clinical disease severity was length of hospital stay (LOS). A random-effects model was used to conduct the meta-analyses. RESULTS: Twenty-one studies involving 4,280 patients were included. The overall quality of evidence applying the GRADE approach ranged from moderate for oxygen requirements to low for all other outcomes. No significant differences in length of hospital stay (LOS) (mean difference (MD) -0.20 days, 95% CI -0.94, 0.53, p = 0.59), or mortality (RR 2.44, 95% CI 0.86, 6.91, p = 0.09) were documented in subjects with viral co-infections compared to those with a single viral infection. There was no evidence for differences in effects across age subgroups in post hoc analyses with the exception of the higher mortality in preschool children (RR 9.82, 95% CI 3.09, 31.20, p<0.001) with viral co-infection as compared to other age groups (I2 for subgroup analysis 64%, p = 0.04). CONCLUSIONS: No differences in clinical disease severity between viral co-infections and single respiratory infections were documented. The suggested increased risk of mortality observed amongst children with viral co-infections requires further investigation.

Benchmarking therapeutic drug monitoring software: A systematic evaluation of available computer tools

Objectives: Therapeutic drug monitoring (TDM) aims at optimizing treatment by individualizing dosage regimen based on blood concentrations measurement. Maintaining concentrations within a target range requires pharmacokinetic (PK) and clinical capabilities. Bayesian calculation represents a gold standard in TDM approach but requires computing assistance. The aim of this benchmarking was to assess and compare computer tools designed to support TDM clinical activities.¦Methods: Literature and Internet were searched to identify software. Each program was scored against a standardized grid covering pharmacokinetic relevance, user-friendliness, computing aspects, interfacing, and storage. A weighting factor was applied to each criterion of the grid to consider its relative importance. To assess the robustness of the software, six representative clinical vignettes were also processed through all of them.¦Results: 12 software tools were identified, tested and ranked. It represents a comprehensive review of the available software characteristics. Numbers of drugs handled vary from 2 to more than 180, and integration of different population types is available for some programs. Nevertheless, 8 programs offer the ability to add new drug models based on population PK data. 10 computer tools incorporate Bayesian computation to predict dosage regimen (individual parameters are calculated based on population PK models). All of them are able to compute Bayesian a posteriori dosage adaptation based on a blood concentration while 9 are also able to suggest a priori dosage regimen, only based on individual patient covariates. Among those applying Bayesian analysis, MM-USC*PACK uses a non-parametric approach. The top 2 programs emerging from this benchmark are MwPharm and TCIWorks. Others programs evaluated have also a good potential but are less sophisticated or less user-friendly.¦Conclusions: Whereas 2 software packages are ranked at the top of the list, such complex tools would possibly not fit all institutions, and each program must be regarded with respect to individual needs of hospitals or clinicians. Programs should be easy and fast for routine activities, including for non-experienced users. Although interest in TDM tools is growing and efforts were put into it in the last years, there is still room for improvement, especially in terms of institutional information system interfacing, user-friendliness, capability of data storage and automated report generation.

Physical activity level and health-related quality of life in the general adult population: a systematic review.

OBJECTIVE: Little is known regarding health-related quality of life and its relation with physical activity level in the general population. Our primary objective was to systematically review data examining this relationship. METHODS: We systematically searched MEDLINE, EMBASE, CINAHL, and PsycINFO for health-related quality of life and physical activity related keywords in titles, abstracts, or indexing fields. RESULTS: From 1426 retrieved references, 55 citations were judged to require further evaluation. Fourteen studies were retained for data extraction and analysis; seven were cross-sectional studies, two were cohort studies, four were randomized controlled trials and one used a combined cross sectional and longitudinal design. Thirteen different methods of physical activity assessment were used. Most health-related quality of life instruments related to the Medical Outcome Study SF-36 questionnaire. Cross-sectional studies showed a consistently positive association between self-reported physical activity and health-related quality of life. The largest cross-sectional study reported an adjusted odds ratio of "having 14 or more unhealthy days" during the previous month to be 0.40 (95% Confidence Interval 0.36-0.45) for those meeting recommended levels of physical activity compared to inactive subjects. Cohort studies and randomized controlled trials tended to show a positive effect of physical activity on health-related quality of life, but similar to the cross-sectional studies, had methodological limitations. CONCLUSION: Cross-sectional data showed a consistently positive association between physical activity level and health-related quality of life. Limited evidence from randomized controlled trials and cohort studies precludes a definitive statement about the nature of this association.

Public health significance of bipolar disorder: implications for early intervention and prevention.

OBJECTIVES: Early intervention and preventive strategies have become major targets of research and service development in psychiatry over the last few years. Compared to schizophrenia, bipolar disorder (BD) has received limited attention in this regard. In this paper, we review the available literature in order to explore the public health significance of BD and the extent to which this may justify the development of early intervention strategies for this disorder. METHODS: The main computerized psychiatric literature databases were accessed. This included Medline and PsychInfo, using the following keywords: bipolar, early intervention, staging model, burden, caregiver, public health, and manic depression. RESULTS: BD is often recurrent and has an impact that goes well beyond symptomatic pathology. The burden it incurs is linked not only to its cardinal clinical features, but also to cognitive dysfunction, poor functional outcome, poor physical health, high rate of comorbidities, and suicide. At a societal level, BD induces enormous direct and indirect costs and has a major impact on caregivers. The available literature reveals a usually long delay between illness onset and the start of treatment, and the absence of specific guidelines for the treatment of the early phase of BD. CONCLUSIONS: Considering the major impact of BD on patients and society, there is an urgent need for the development of early intervention strategies aimed at earlier detection and more specific treatment of the early phase of the disorder.

The ecological significance of arbuscular mycorrhizal fungal effects on clonal reproduction in plants

The population ecology of clonal plants depends on the number and distribution of ramets formed during growth. Variation in clonal reproduction has previously been explained by variation in effects of abiotic resource heterogeneity and by plant genotypic variation. Different co-occurring species of the mutualistic arbuscular mycorrhizal fungi (AMF) have been shown to differentially alter growth traits of Prunella vulgaris which we hypothesize would lead to changes in clonal reproduction. Two experiments were carried out to test whether different co-occurring mycorrhizal fungi significantly influence clonal reproduction of P. vulgaris whether this effect also occurs when P. vulgaris is growing in an artificial plant community and how the effects compare with plant genotype effects on clonal growth of P. vulgaris. In the first experiment the number of ramets of P. vulgaris growing in a plant community of simulated calcareous grassland was significantly affected by inoculation with different mycorrhizal fungi. The number of ramets produced by P. vulgaris differed by a factor of up to 1.8 with different mycorrhizal fungi. The fungal effects on the number of new ramets were independent of their effects on the biomass of P. vulgaris. In a second experiment 17 different genotypes of P. vulgaris were inoculated with different mycorrhizal fungi. There were significant main effects of genotypes and mycorrhizal fungi on clonal reproduction of P. vulgaris. The effect of different mycorrhizal fungi contributed more than the effect of plant genotype to variation in size and ramet production. However mean stolon length and spacer length which determine the spatial arrangement of ramets were only significantly affected by plant genotype. There were no mycorrhizal fungal X plant genotype interactions on clonal growth of P. vulgaris indicating that there is no obvious evidence that selection pressures would favor further coevolution between P. vulgaris and mycorrhizal fungal species. In natural communities plants can be colonized by several different AMF at the same time. The effect of the mixed AMF treatment on the growth and clonal reproduction of P. vulgaris could not be predicted from the responses of the plants to the single AMF To what extent however the patterns of colonization by different AMF differ among plants in a natural community is unknown. Since the effects of AMF on growth and clonal reproduction occur on a population of P. vulgaris in a microcosm plant community and because the effects are also as great as those caused by plant genotypic variation we conclude that the effects are strong enough to potentially affect population size and variation of clonal plants in communities.

The systematic profiling of false identity documents: method validation and performance evaluation using seizures known to originate from common and different sources

False identity documents constitute a potential powerful source of forensic intelligence because they are essential elements of transnational crime and provide cover for organized crime. In previous work, a systematic profiling method using false documents' visual features has been built within a forensic intelligence model. In the current study, the comparison process and metrics lying at the heart of this profiling method are described and evaluated. This evaluation takes advantage of 347 false identity documents of four different types seized in two countries whose sources were known to be common or different (following police investigations and dismantling of counterfeit factories). Intra-source and inter-sources variations were evaluated through the computation of more than 7500 similarity scores. The profiling method could thus be validated and its performance assessed using two complementary approaches to measuring type I and type II error rates: a binary classification and the computation of likelihood ratios. Very low error rates were measured across the four document types, demonstrating the validity and robustness of the method to link documents to a common source or to differentiate them. These results pave the way for an operational implementation of a systematic profiling process integrated in a developed forensic intelligence model.

Systematic and exclusive use of intravascular ultrasound for endovascular aneurysm repair - the Lausanne experience.

Five years of experience with endovascular infrarenal aneurysm repair at our institution is reviewed. Implantation of endoprostheses in 88 patients has been performed by surgeons using exclusively intravascular ultrasound (IVUS) and fluoroscopy. IVUS identified the target site of deployment in all cases. In-hospital morbidity was 22% (19/88). Two percent mortality (2/88) and 5% early conversion (4/88) as a consequence of type I endoleaks were noted only in the first 53 patients with early devices (NS). Early endoleaks were present in 36% (32/88) including twenty-two type I, five type II and five type III endoleaks. Proximal endoleaks were associated with early devices (P<0.001), and technical difficulties with deployment. Tube grafts used in the beginning, performed poorly with 54% (7/13) type I endoleaks. Endoleaks diminished to 10% (9/88) by spontaneous closure and secondary endovascular procedures that were necessary in 24% (21/88) and consisted of coil embolization/cuff extension (9), late conversion (6), and limb recanalization or femoral cross-over bypass (6). Endovascular aneurysm repair using IVUS is a valid alternative technique. Improved devices and systematic use of bifurcated endoprostheses for infrarenal aneurysms reduce the occurrence of type I endoleaks.

Fracture rates of IPS Empress all-ceramic crowns: a systematic review.

Purpose: The aim of this study was to evaluate the clinical fracture rate of crowns fabricated with the pressable, leucite-reinforced ceramic IPS Empress, and relate the results to the type of tooth restored. Materials and Methods: The database SCOPUS was searched for clinical studies involving full-coverage crowns made of IPS Empress. To assess the fracture rate of the crowns in relation to the type of restored tooth and study, Poisson regression analysis was used. Results: Seven clinical studies were identified involving 1,487 adhesively luted crowns (mean observation time: 4.5 +/- 1.7 years) and 81 crowns cemented with zinc-phosphate cement (mean observation time: 1.6 +/- 0.8 years). Fifty-seven of the adhesively luted crowns fractured (3.8%). The majority of fractures (62%) occurred between the third and sixth year after placement. There was no significant influence regarding the test center on fracture rate, but the restored tooth type played a significant role. The hazard rate (per year) for crowns was estimated to be 5 in every 1,000 crowns for incisors, 7 in every 1,000 crowns for premolars, 12 in every 1,000 crowns for canines, and 16 in every 1,000 crowns for molars. One molar crown in the zinc-phosphate group fractured after 1.2 years. Conclusion: Adhesively luted IPS Empress crowns showed a low fracture rate for incisors and premolars and a somewhat higher rate for molars and canines. The sample size of the conventionally luted crowns was too small and the observation period too short to draw meaningful conclusions. Int J Prosthodont 2010;23:129-133.

Looking for factors involved in the light-dependent degradation of phytochrome A

SUMMARY : Phytochromes constitute a family of red/far-red photoreceptors regulating all the major transitions during the life cycle of plants. In Arabidopsis, five members: phyA,_ B, C, D and E, were identified. Phytochromes are synthesized in their inactive red-light absorbing form called Pr. Upon light absorbance they convert to the far-red light absorbing Pfr form. The Pfr form is the active conformer which converts back to the Pr form either rapidly upon far-red perception or in a slower process called dark reversion. ph~A represents an exception, in that it does not significantly dark-revert and two specific processes have been developed by the plants to decrease the amount of biologically active phyA. The first one is alight-dependent repression of the PHYA gene expression and the second one is alight-dependent degradation of the phyA protein. The latter is the most efficient process to rapidly decrease the level of active phyA. The ability of plants to regulate the amount of active phyA is critical in a far-red rich environment, a situation observed under a canopy. In these conditions, phyA is essential to induce the germination and the deetiolation of the young seedling. Later in the development the ability of phyA to repress growth counteracts the shade avoidance response. Therefore decreasing the amount of phyA allows stem growth and to compete with neighbours for the light. In this thesis, I investigate the light-dependent degradation of phyA. I developed a reverse genetic approach based on the systematic analysis of the light-dependent accumulation of phyA in the different cullin mutant cull, cul3a; cul3b and cul4. This analysis allowed me to show that CUL1 and CUL3A-based E3 ligase complexes are involved in the regulation of phyA degradation. Surprisingly, our results also demonstrate that cu14 is not affected in the degradation of phyA whereas constitutive Photomorphogenic 1 (COP1) a subunit of one CUL4based E3 complex was reported to be involved. Further investigations showed that the phenotype of cop1 is conditional, the mutant being defective in phyA degradation only in the presence of metabolisable sugars. I also showed that phyA is degraded by a proteasome-dependent mechanism both in the cytoplasm and in the nucleus using mutants and transgenic lines affected in the localization of phyA. Interestingly, I observed that phyA degradation was faster in the nucleus than in the cytosol and that rapid degradation of Pr also occurred in the nucleus suggesting that cytosolic accumulation of phyA in the dark is a way to regulate its proteolysis. Finally, we identify a short region similar to a PEST sequence required for phyA stability and we developed a unbiased genetic screen to identify new components involved in the regulation of the light-dependent degradation of phyA. The significance of these results are discussed. RESUME : Les phytochromes (phy) constituent une famille de photorécepteurs absorbant la lumière rouge et rouge lointaine et régulant toutes les étapes de transitions majeures dans la vie des plantes. Chez Arabidopsis, cinq membres : phyA, B, C, D et E ont été identifiés. Les phytochromes sont synthétisés sous une forme inactive appelée Pr absorbant la lumière rouge. Après perception de lumière ils passent sous une forme active Pfr absorbant dans le rouge lointain. La forme Pfr peut retourner sous la forme Pr après absorption de lumiëre rouge lointaine ou dans un processus lent appelé «réversion à l'obscurité ». phyA représente une exception à cette règle car il ne retoune pas significativement sous sa forme inactive dans le noir. Deux processus spécifiques ont donc été développés pour diminuer le taux de phyA actif. Le premier consiste en la répression du gène PHYA en condition de lumière et le second en une dégradation induite par la lumière de la protéine phyA. Ce dernier processus est le plus efficace pour diminuer rapidement le niveau de phyA. La capacité des plantes à réguler le taux de phyA actifs est critique dans un environnement riche en lumière rouge lointaine, une situation observée sous une canopée. Sous une canopée, phyA est essentiel pour induire la germination et la dé-étiolation de la jeune pousse. Plus tard dans le développement la capacité de phyA de réprimer la croissance freine la «réponse à l'évitement de l'ombre ». Par conséquent diminuer le taux de phyA permet la croissance de la tige et donc de rentrer en compétition pour la lumière avec les plantes avoisinantes. Dans cette thèse, j'ai étudié la dégradation de phyA. J'ai développé une approche génétique inverse basée sur l'analyse systématique de l'accumulation de phyA en condition de lumière dans les différents mutants cullin, cul1, cul3a, cul3b et cul4. Ces analyses nous ont permis d'identifier qu'un complexe E3 ligase CUL1 et un complexe E3 ligase CUL3A sont impliqués dans la régulation de la dégradation de phyA. Mes résultats démontrent aussi que le mutant cul4 n'est pas affecté dans la dégradation de phyA alors que Çonstitutive Photomorphogenic 1 (COPI) une sous unité d'un complexe CUL4 à été identifier dans la régulation de cette dégradation. Des analyses supplémentaires suggèrent que l'effet de la mutation cop1 est dépendante dë la présence de sucres métabolisables. J'ai aussi montré que phyA est dégradé dans le noyau et dans le cytoplasme par un mécanisme dépendant du protéasome et que la dégradation dans le.noyau est non seulement aspécifique de la forme Pr ou Pfr mais aussi est plus rapide que dans le cytoplasme. Ceci suggère que l'accumulation de phyA dans le cytoplasme permet son accumulation à des niveaux élevés à l'obscurité. Enfin j'ai identifié une région similaire à un motif PEST requise pour la stabilité de phyA et j'ai aussi développé un criblage génétique non biaisé pour identifier de nouveaux composants impliqués dans la régulation de la dégradation de phyA. L'importance de ces résultats est discutée dans le dernier chapitre de cette thèse.