Cost effectiveness of OptiMal® rapid diagnostic test for malaria in remote areas of the Amazon Region, Brazil

Abstract Background In areas with limited structure in place for microscopy diagnosis, rapid diagnostic tests (RDT) have been demonstrated to be effective. Method The cost-effectiveness of the Optimal® and thick smear microscopy was estimated and compared. Data were collected on remote areas of 12 municipalities in the Brazilian Amazon. Data sources included the National Malaria Control Programme of the Ministry of Health, the National Healthcare System reimbursement table, hospitalization records, primary data collected from the municipalities, and scientific literature. The perspective was that of the Brazilian public health system, the analytical horizon was from the start of fever until the diagnostic results provided to patient and the temporal reference was that of year 2006. The results were expressed in costs per adequately diagnosed cases in 2006 U.S. dollars. Sensitivity analysis was performed considering key model parameters. Results In the case base scenario, considering 92% and 95% sensitivity for thick smear microscopy to Plasmodium falciparum and Plasmodium vivax, respectively, and 100% specificity for both species, thick smear microscopy is more costly and more effective, with an incremental cost estimated at US$549.9 per adequately diagnosed case. In sensitivity analysis, when sensitivity and specificity of microscopy for P. vivax were 0.90 and 0.98, respectively, and when its sensitivity for P. falciparum was 0.83, the RDT was more cost-effective than microscopy. Conclusion Microscopy is more cost-effective than OptiMal® in these remote areas if high accuracy of microscopy is maintained in the field. Decision regarding use of rapid tests for diagnosis of malaria in these areas depends on current microscopy accuracy in the field.

Bilateral mesiodens in monozygotic twins: 3D diagnostic and management

Mesiodens is the most frequent type of supernumerary tooth and may occur in several forms, causing different local disorders, such as impaction of the anterior permanent teeth. High-resolution three-dimensional (3D) images have improved the diagnosis and treatment plan of patients with impacted and supernumerary teeth. The purpose of this paper was to report a case of two mesiodens in monozygotic twin boys with appropriate 3D diagnostic and treatment plan

Transcription profiling in papillary thyroid carcinoma reveals potential diagnostic markers and drug targets

Financial support FAPESP and CAPES.

Copy number variation in Williams-Beuren syndrome: suitable diagnostic strategy for developing countries

Abstract Background Williams-Beuren syndrome (WBS; OMIM 194050) is caused by a hemizygous contiguous gene microdeletion at 7q11.23. Supravalvular aortic stenosis (SVAS), mental retardation, and overfriendliness comprise typical symptoms of WBS. Although fluorescence in situ hybridization (FISH) is considered the gold standard technique, the microsatellite DNA markers and multiplex ligation-dependent probe amplification (MLPA) could be used for to confirm the diagnosis of WBS. Results We have evaluated a total cohort of 88 patients with a suspicion clinical diagnosis of WBS using a collection of five markers (D7S1870, D7S489, D7S613, D7S2476, and D7S489_A) and a commercial MLPA kit (P029). The microdeletion was present in 64 (72.7%) patients and absent in 24 (27.3%) patients. The parental origin of deletion was maternal in 36 of 64 patients (56.3%) paternal in 28 of 64 patients (43.7%). The deletion size was 1.55 Mb in 57 of 64 patients (89.1%) and 1.84 Mb in 7 of 64 patients (10.9%). The results were concordant using both techniques, except for four patients whose microsatellite markers were uninformative. There were no clinical differences in relation to either the size or parental origin of the deletion. Conclusion MLPA was considered a faster and more economical method in a single assay, whereas the microsatellite markers could determine both the size and parental origin of the deletion in WBS. The microsatellite marker and MLPA techniques are effective in deletion detection in WBS, and both methods provide a useful diagnostic strategy mainly for developing countries.

Diagnostic methods in sepsis: the need of speed

OBJECTIVE: Sepsis is a common condition encountered in hospital environments. There is no effective treatment for sepsis, and it remains an important cause of death at intensive care units. This study aimed to discuss some methods that are available in clinics, and tests that have been recently developed for the diagnosis of sepsis. METHODS: A systematic review was performed through the analysis of the following descriptors: sepsis, diagnostic methods, biological markers, and cytokines. RESULTS: The deleterious effects of sepsis are caused by an imbalance between the invasiveness of the pathogen and the ability of the host to mount an effective immune response. Consequently, the host's immune surveillance fails to eliminate the pathogen, allowing it to spread. Moreover, there is a pro-inflammatory mediator release, inappropriate activation of the coagulation and complement cascades, leading to dysfunction of multiple organs and systems. The difficulty achieve total recovery of the patient is explainable. There is an increased incidence of sepsis worldwide due to factors such as aging population, larger number of surgeries, and number of microorganisms resistant to existing antibiotics. CONCLUSION: The search for new diagnostic markers associated with increased risk of sepsis development and molecules that can be correlated to certain steps of sepsis is becoming necessary. This would allow for earlier diagnosis, facilitate patient prognosis characterization, and prediction of possible evolution of each case. All other markers are regrettably constrained to research units.

Performance of six diagnostic tests to screen for Chagas disease in blood banks and prevalence of Trypanosoma cruzi infection among donors with inconclusive serology screening based on the analysis of epidemiological variables

OBJECTIVE: The frequent occurrence of inconclusive serology in blood banks and the absence of a gold standard test for Chagas'disease led us to examine the efficacy of the blood culture test and five commercial tests (ELISA, IIF, HAI, c-ELISA, rec-ELISA) used in screening blood donors for Chagas disease, as well as to investigate the prevalence of Trypanosoma cruzi infection among donors with inconclusive serology screening in respect to some epidemiological variables. METHODS: To obtain estimates of interest we considered a Bayesian latent class model with inclusion of covariates from the logit link. RESULTS: A better performance was observed with some categories of epidemiological variables. In addition, all pairs of tests (excluding the blood culture test) presented as good alternatives for both screening (sensitivity > 99.96% in parallel testing) and for confirmation (specificity > 99.93% in serial testing) of Chagas disease. The prevalence of 13.30% observed in the stratum of donors with inconclusive serology, means that probably most of these are non-reactive serology. In addition, depending on the level of specific epidemiological variables, the absence of infection can be predicted with a probability of 100% in this group from the pairs of tests using parallel testing. CONCLUSION: The epidemiological variables can lead to improved test results and thus assist in the clarification of inconclusive serology screening results. Moreover, all combinations of pairs using the five commercial tests are good alternatives to confirm results.

What is the diagnostic value of ultrasonography compared to physical evaluation in patients with idiopathic carpal tunnel syndrome?

[EN] OBJECTIVE: Our hypothesis is that sonography performed by the rheumatologist in patients with suspected carpal tunnel syndrome (CTS) has higher diagnostic value compared to physical evaluation. METHODS: Adult patients with suspected idiopathic CTS, defined by sensory symptoms over the distribution of the median nerve with or without positive results with the Phalen and/or the Tinel's maneuvers were included. The diagnosis of CTS was indicated by typical symptoms daily for at least 3 months and a positive nerve conduction study. One rheumatologist unaware of the clinical and electrodiagnostic results performed an ultrasound examination of the median nerve for the area ranging from the inlet to the outlet of the carpal tunnel. Mean cross-sectional area at each level, flattening ratio and bowing of flexor retinaculum were obtained. RESULTS: Sixty-eight patients with 105 affected wrists were examined. Tinel's and Phalen's signs had a closer sensitivity (73% and 67% respectively) and specificity (40% and 30% respectively). The best swelling nerve cut-off by sonography was 9.7 mm2 at the tunnel inlet, with a sensitivity of 86%, a specificity of 48% and accuracy of 77%. A 100% positive predictive value was reached with a cross-sectional area of 13 mm2, involving 33 hands (31% of the whole sample). Maximal cross sectional area and the measurement of flexor retinaculum had an accuracy of 72% and 73% respectively. Combination of physical maneuvers and sonography not yielded more accuracy than cross-sectional area itself. CONCLUSION: In patients with clinical history of idiopathic CTS and positive nerve conduction study, sonography performed by the rheumatologist has higher diagnostic value than physical maneuvers.

Diagnostic techniques for EHD and MHD interaction

The impact of plasma technologies is growing both in the academic and in the industrial fields. Nowadays, a great interest is focused in plasma applications in aeronautics and astronautics domains. Plasma actuators based on the Magneto-Hydro-Dynamic (MHD) and Electro- Hydro-Dynamic (EHD) interactions are potentially able to suitably modify the fluid-dynamics characteristics around a flying body without utilizing moving parts. This could lead to the control of an aircraft with negligible response time, more reliability and improvements of the performance. In order to study the aforementioned interactions, a series of experiments and a wide number of diagnostic techniques have been utilized. The EHD interaction, realized by means of a Dielectric Barrier Discharge (DBD) actuator, and its impact on the boundary layer have been evaluated by means of two different experiments. In the first one a three phase multi-electrode flat panel actuator is used. Different external flow velocities (from 1 to 20m/s) and different values of the supplied voltage and frequency have been considered. Moreover a change of the phase sequence has been done to verify the influence of the electric field existing between successive phases. Measurements of the induced speed had shown the effect of the supply voltage and the frequency, and the phase order in the momentum transfer phenomenon. Gains in velocity, inside the boundary layer, of about 5m/s have been obtained. Spectroscopic measurements allowed to determine the rotational and the vibrational temperature of the plasma which lie in the range of 320 ÷ 440°K and of 3000 ÷ 3900°K respectively. A deviation from thermodynamic equilibrium had been found. The second EHD experiment is realized on a single electrode pair DBD actuator driven by nano-pulses superimposed to a DC or an AC bias. This new supply system separates the plasma formation mechanism from the acceleration action on the fluid, leading to an higher degree of the control of the process. Both the voltage and the frequency of the nano-pulses and the amplitude and the waveform of the bias have been varied during the experiment. Plasma jets and vortex behavior had been observed by means of fast Schlieren imaging. This allowed a deeper understanding of the EHD interaction process. A velocity increase in the boundary layer of about 2m/s had been measured. Thrust measurements have been performed by means of a scales and compared with experimental data reported in the literature. For similar voltage amplitudes thrust larger than those of the literature, had been observed. Surface charge measurements led to realize a modified DBD actuator able to obtain similar performances when compared with that of other experiments. However in this case a DC bias replacing the AC bias had been used. MHD interaction experiments had been carried out in a hypersonic wind tunnel in argon with a flow of Mach 6. Before the MHD experiments a thermal, fluid-dynamic and plasma characterization of the hypersonic argon plasma flow have been done. The electron temperature and the electron number density had been determined by means of emission spectroscopy and microwave absorption measurements. A deviation from thermodynamic equilibrium had been observed. The electron number density showed to be frozen at the stagnation region condition in the expansion through the nozzle. MHD experiments have been performed using two axial symmetric test bodies. Similar magnetic configurations were used. Permanent magnets inserted into the test body allowed to generate inside the plasma azimuthal currents around the conical shape of the body. These Faraday currents are responsible of the MHD body force which acts against the flow. The MHD interaction process has been observed by means of fast imaging, pressure and electrical measurements. Images showed bright rings due to the Faraday currents heating and exciting the plasma particles. Pressure measurements showed increases of the pressure in the regions where the MHD interaction is large. The pressure is 10 to 15% larger than when the MHD interaction process is silent. Finally by means of electrostatic probes mounted flush on the test body lateral surface Hall fields of about 500V/m had been measured. These results have been used for the validation of a numerical MHD code.

Il corpo e l'individuo tra proprietà ed autodeterminazione. Con particolare riferimento al fenomeno delle biobanche

La bioetica è il luogo ideale per cercare risposte ai grandi interrogativi concernenti la vita, la morte e la cura dell'essere umano. I recenti dibattiti sull'uso, ed il temuto abuso, del corpo umano in medicina hanno messo in evidenza la necessità di una discussione approfondita sul potere di scelta che l'individuo può esercitare sulla propria mente e sul proprio corpo. Spinta dal desidero di indagare l'estensione di tale potere di scelta ho voluto analizzare le tematiche riguardanti “il corpo”, “l'individuo”, “la proprietà” e “l'autodeterminazione”. L'analisi è stata condotta individuando alcuni dei differenti significati che questi termini assumono nei diversi ambiti che la bioetica lambisce e mostrando, in particolare, la visione di tale realtà attraverso le lenti del giurista. A chi appartiene il corpo? Chi ha il potere di decidere su di esso? Il potere di scelta valica gli antichi i confini legati al corpo del paziente e coinvolge tessuti, organi e cellule staccati dal corpo umano, parti che un tempo erano considerati scarti operatori sono oggi divenuti tesori inestimabili per la ricerca. L'importanza assunta dai campioni biologici ha portato alla creazione di biobanche nelle quali sono raccolti, catalogati e il DNA studiato in campioni biologici Le biobanche riflettono le tensioni della bioetica e del biodititto. Lo studio delle biobanche riguarda, tra l'altro, la riceca dell'equilibrio tra le diverse esigenze meritevoli di tutela: in primo luogo il diritto alla privacy, diritto a che le “proprie informazioni” non vengano divulgate ed il diritto a non essere discriminato ed in secondo luogo le necessità dettate dalla ricerca e dalla scienza medica. Nel 2009 la rivista Times messo biobanche tra le 10 idee in grado di cambiare il mondo anche in considarazione della medicina personalizzata e del fatto che costituiscono una la speranza per la ricerca contro le malattie attuali e future.

Human papillomavirus (HPV) and associated diseases: between applied diagnostic and basic research

Human Papillomavirus (HPV) is the cause of cervical cancers (among these, adenocarcinoma, AdCa) and is associated to a subgroup of oropharyngeal carcinomas (OPSCCs). Even if the risk for cancer development is linked to the infection by some viral genotypes, mainly HPV16 and 18, viral DNA alone seems not to be sufficient for diagnosis. Moreover, the role of the virus in OPSCCs has not been totally clarified yet. In the first part of the thesis, the performances concerning viral genotyping in clinical cervical samples of a new pyrosequencing-based test and a well-known hybridization-based assay have been compared. Similar results between the methods have been obtained. However, the former showed advantages in detecting intratype variants, higher specificity and a broader spectrum of detectable HPV types. The second part deals with the evaluation of virological markers (genotyping, viral oncoproteins expression, viral load, physical state and CpG methylation of HPV16 genome) in the diagnosis/prognosis of cervical AdCa and HPV-associated OPSCCs. HPV16 has been confirmed the most prevalent genotype in both the populations. Interestingly, the mean methylation frequency of viral DNA at the early promoter showed the tendency to be associated to invasion for cervical AdCa and to a worse prognosis for OPSCCs, suggesting a promising role as diagnostic/prognostic biomarker. The experiments of the third part were performed at the DKFZ in Heidelberg (Germany) and dealt with the analysis of the response to IFN-k transfection in HPV16-positive cervical cancer and head&neck carcinoma cell lines to evaluate its potential role as new treatment. After 24h, we observed increased IFN-b expression which lead to the up-regulation of genes involved in the antigens presentation pathway (MHC class I and immunoproteasome) and antiviral response as well, in particular in cervical cancer cell lines. This fact suggested also the presence of different HPV-mediated carcinogenic pathways between the two anatomical districts.

Aging of nuclear power plant cables: in search of non-destructive diagnostic quantities

The safety systems of nuclear power plants rely on low-voltage power, instrumentation and control cables. Inside the containment area, cables operate in harsh environments, characterized by relatively high temperature and gamma-irradiation. As these cables are related to fundamental safety systems, they must be able to withstand unexpected accident conditions and, therefore, their condition assessment is of utmost importance as plants age and lifetime extensions are required. Nowadays, the integrity and functionality of these cables are monitored mainly through destructive test which requires specific laboratory. The investigation of electrical aging markers which can provide information about the state of the cable by non-destructive testing methods would improve significantly the present diagnostic techniques. This work has been made within the framework of the ADVANCE (Aging Diagnostic and Prognostics of Low-Voltage I\&C Cables) project, a FP7 European program. This Ph.D. thesis aims at studying the impact of aging on cable electrical parameters, in order to understand the evolution of the electrical properties associated with cable degradation. The identification of suitable aging markers requires the comparison of the electrical property variation with the physical/chemical degradation mechanisms of polymers for different insulating materials and compositions. The feasibility of non-destructive electrical condition monitoring techniques as potential substitutes for destructive methods will be finally discussed studying the correlation between electrical and mechanical properties. In this work, the electrical properties of cable insulators are monitored and characterized mainly by dielectric spectroscopy, polarization/depolarization current analysis and space charge distribution. Among these techniques, dielectric spectroscopy showed the most promising results; by means of dielectric spectroscopy it is possible to identify the frequency range where the properties are more sensitive to aging. In particular, the imaginary part of permittivity at high frequency, which is related to oxidation, has been identified as the most suitable aging marker based on electrical quantities.

Experimental assessment of environmental decay effects in masonry via non destructive diagnostic techniques and mechanical tests

Environmental decay in porous masonry materials, such as brick and mortar, is a widespread problem concerning both new and historic masonry structures. The decay mechanisms are quite complex dependng upon several interconnected parameters and from the interaction with the specific micro-climate. Materials undergo aesthetical and substantial changes in character but while many studies have been carried out, the mechanical aspect has been largely understudied while it bears true importance from the structural viewpoint. A quantitative assessment of the masonry material degradation and how it affects the load-bearing capacity of masonry structures appears missing. The research work carried out, limiting the attention to brick masonry addresses this issue through an experimental laboratory approach via different integrated testing procedures, both non-destructive and mechanical, together with monitoring methods. Attention was focused on transport of moisture and salts and on the damaging effects caused by the crystallization of two different salts, sodium chloride and sodium sulphate. Many series of masonry specimens, very different in size and purposes were used to track the damage process since its beginning and to monitor its evolution over a number of years Athe same time suitable testing techniques, non-destructive, mini-invasive, analytical, of monitoring, were validated for these purposes. The specimens were exposed to different aggressive agents (in terms of type of salt, of brine concentration, of artificial vs. open-air natural ageing, …), tested by different means (qualitative vs. quantitative, non destructive vs. mechanical testing, punctual vs. wide areas, …), and had different size (1-, 2-, 3-header thick walls, full-scale walls vs. small size specimens, brick columns and triplets vs. small walls, masonry specimens vs. single units of brick and mortar prisms, …). Different advanced testing methods and novel monitoring techniques were applied in an integrated holistic approach, for quantitative assessment of masonry health state.

Sleep motor activity in parkinsonian syndromes at onset: a prospective study to determine potential diagnostic and prognostic markers

Aim of this study is to describe the possible diagnostic value of sleep disturbances in the differential diagnosis of neurodegenerative diseases characterized by parkinsonism at onset. 42 consecutive patients with parkinsonian features and disease duration up to 3 years were included in the BO-ProPark study. Each patient was evaluated twice, at baseline (T0) and 16 months later (T1). Patients were diagnosed as Parkinson disease (PD, 27 patients), PD plus (PD with cognitive impairment/dementia or dysautonomia, 4 patients) and parkinsonian syndrome (PS, 11 patients). All patients underwent a full night video-polysomnography scored by a neurologist blinded to the clinical diagnosis. Sleep efficiency and total sleep time were reduced in all patients; wake after sleep onset was higher in patients with atypical parkinsonisms than in PD patients. No significant differences between groups of patients were detected in other sleep parameters. The mean percentage of epochs with enhanced tonic muscle EMG activity during REM sleep was higher in PD plus and PS than in PD. No difference in phasic muscle EMG activity during REM sleep was seen between the two groups. REM behaviour disorder was more frequent in PD plus and PS than in PD patients. Our data suggest that REM sleep motor control is more frequently impaired at disease onset in patients with PS and PD plus compared to PD patients. The presence of RBD or an enhanced tonic muscle EMG activity in a patient with recent onset parkinsonian features should suggest a diagnosis of atypical parkinsonism, rather than PD. More data are needed to establish the diagnostic value of these features in the differential diagnosis of parkinsonisms. The evaluation of sleep disorders may be a useful tool in the differential diagnosis of parkinsonism at onset.