Appropriateness of internal digital phantoms for monitoring the stability of the UBIS 5000 quantitative ultrasound device in clinical trials.

In bone status assessment, proper quality assurance/quality control is crucial since changes due to disease or therapeutic treatment are very small, in the order of 2-5%. Unlike for dual X-ray absorptiometry, quality control procedures have not been extensively developed and validated for quantitative ultrasound technology, limiting its use in longitudinal monitoring. While the challenge of developing an ideal anthropometric phantom is still open, some manufacturers use the concept of the internal digital phantom mimicking human characteristics to check the stability of their device. The objective of the study was to develop a sensitive model of quality control suitable for the correction of QUS patient data. In order to achieve this goal, we simulated a longitudinal device lifetime with both correct and malfunctioning behaviors. Then, we verified the efficiency of digital phantoms in detecting those changes and subsequently established the in vitro/in vivo relationship. This is the first time that an attempt to validate an internal digital phantom has made, and that this type of validation approach is used. The digital phantom (DP) was designed to mimic normal bone (BUAP2) and osteoporotic bone (BUAP1) properties. The DP was studied using the UBIS 5000 ultrasound device (DMS, France). Diverse malfunctions of the UBIS-5000 were simulated. Several series of measurements were performed on both BUAP1 and 2 and on 12 volunteers at each grade of malfunction. The effect of each simulated malfunction on in vivo and in vitro results was presented graphically by plotting the average BUA values against the percentage change from baseline. The change from baseline in BUA was modeled using linear regression, and the in vivo/in vitro ratio was obtained from the model. All experimentations influenced the measure of BUAP1 and 2 as well as the measure of our 12 volunteers. However, the degree of significance varied as a function of the severity of the malfunction, and the results also differed substantially in magnitude between in vivo and in vitro. Indeed, the DP was about 10 times more sensitive to variations of the transfer function than was the in vivo measurement, which is very reassuring. The sensitivity of the digital phantoms was reliable in the determination of simulated malfunctions of the UBIS-5000. The digital phantoms provided an accurate evaluation of the acoustic performance of the scanner, including the fidelity of transducers. In light of these results, the QC approach of the UBIS-5000 will be extremely simple to implement compared with other devices. Indeed, since the digital phantom was automatically measured during every patient measurement, the QC approach could be built on an individual level basis rather than on an average basis.

Longitudinal quality control methodology for the quantitative ultrasound Achilles+ in clinical trial settings.

Appropriate quality assurance (QA) and quality control (QC) procedures have been well developed and validated for dual X-ray absorptiometry (DXA), and are widely applied in multicenter clinical trials to monitor device stability used to check the treatment effects on bone mineral density. This is not yet the case for quantitative ultrasound (QUS) technology, for which no QC approaches have yet been fully tested. The first Achilles (GE-Lunar Corporation, Madison, WI, USA) has been on the market for 10 years (1991). The goal of this study was to develop the QC methodology for the QUS Achilles+ device using its past/current experience (log and maintenance files.) as well as by integrating the progress made over the last years in the ultrasound domain so as to better understand the influence of temperature on ultrasound parameters. Because of the lack of confidence in the external black rubber phantom used in daily QC with the Achilles+, to monitor the device stability, we selected several QC parameters known to be influenced by potential malfunctions as experienced by the maintenance department of GE-Lunar company as well as the physical approach. These are phantom temperature-adjusted speed of sound (PSOS-TC) and broadband ultrasound attenuation (PBUA-TC), water speed of sound error (WSE), water spectrum slope (WSS) and water gain (WG). We used four Achilles+ devices perfectly stable during their entire QC range, to calculate the optimum thresholds (based mostly on 95% confidence interval) for each of these parameters as well as the precision for the in vitro SOS and BUA. An additional not fully stable Achilles device has been used to run a QC procedure example. The precision expressed as the CV was 0.22% and 0.65% for the PSOS-TC and PBUA-TC, respectively. The alarm thresholds used for QC process are +/- 0.6%, +/- 1.9%, +/- 6.8 m/s, +/- 5.3% and +/- 7.3% for the PSOS-TC, PBUA-TC, WSE, WSS and WG, respectively. Applying a logical approach on the impact of each parameter on each other as well as their respective reactivity to malfunctions, we build a QC process flowchart meant to detect real malfunction in the daily QC. We found that in case of real malfunctions, the in vivo SOS should be decreased by 1.33 m/s for each 1 m/s increase in WSE. Unfortunately, in vivo BUA can not be adjusted when real malfunction occurs. Nevertheless, the BUA can be qualified as bad quality data and excluded from the medical interpretation. Using the currently available phantom and parameters, the best possible QC procedures to detect long-term drift in the daily QC of the Achilles+ was developed. To fully validate our approach and gain confidence in the defined limits it is our plan to apply this QC processing to a higher number of QUS devices.

Human immunodeficiency virus-1 infection in neonates: correlation of plasma and cellular viremia and clinical outcome. French Pediatric Cohort Study Group.

Among human immunodeficiency virus-1 (HIV-1) vertically infected children, two patterns of disease progression have been observed: about 25% develop a severe immunodeficiency within the first 2 years of life; the rest experience a slower progression, like adults. We have assessed infectious viral burden in infected neonates through the French National Prospective Study. Plasma and cell-associated viremia were assayed by endpoint-dilution cultures in samples from 46 infants followed prospectively from birth. Plasma and cell-associated viral burden were found to be significantly higher in rapid progressing infants than in non-progressing infants in the first months of life: before the age of 2 months, between 2 and 4 months of age and by the age of 6 months. Moreover, among the non-progressing children, the infectious viral burden before the age of 4 months was predictive of the viral burden measured after the age of 12 months. In conclusion, this work demonstrates that infectious viral load is a reliable predictive marker for rapid progression to AIDS in infants and could be useful for initiating antiretroviral therapy.

[Therapeutic management of schizophrenic patients and its cost]. / Etude de la prise en charge thérapeutique des schizophrènes et de son coût.

The purpose of this study was to observe the treatment of patients suffering from schizophrenic disorders and to assess the cost of this treatment in medical and social terms. The survey based on a questionnaire was sent to 6,000 French psychiatrists practising both in the hospital sector and in the ambulatory sector, whether acting through the national health service or privately. The psychiatrists who accepted to answer (N = 494) described all the treatment and assistance undergone by the last patient suffering from schizophrenia, as defined by the DSM III-R, seen either during a consultation or when hospitalized during the previous year. The clinical, epidemiological and therapeutic information collected for 356 patients treated as out-patients (72%) and 138 hospitalized patients (28%) in the public (49%) or private (51%) sectors underwent medical and economic modelling. The most frequent forms of schizophrenia encountered were paranoid type (48.6%) and those which developed chronically without severe exacerbation (32%). The average length of time between the date of the survey and the first symptoms is on average 11 +/- 8 years and the average length of time between the date of the survey and the first symptoms is on average 11 +/- 8 years and the average length of time between the first hospitalization is 9.5 +/- 8 years. This means that the time between the first symptoms and the first hospitalization is 25 +/- 4 months on average. The average number of previous full-time hospitalizations is 4 and the patients spent 22 months (+/- 48) in hospital on a full-time basis and 26 months (+/- 39) as day patients in hospital, from the start of their disorders. 27% of patients had at least one previous suicide attempt and 28% had already committed a medico-legal act.(ABSTRACT TRUNCATED AT 250 WORDS)

[Massive fetomaternal hemorrhage and prevention of fetomaternal Rhesus incompatibility. The failure of our present system of prevention]. / Hémorragie foeto-maternelle massive et prévention de l'incompatibilité Rhésus foeto-maternelle. Une faille de l'organisation actuelle de la prévention.

We had a case where risk of rhesus D feto-maternal immunisation occurred following failure to diagnose feto-maternal haemorrhage (HFM); and it was shown up by rhesus negative mother with a rhesus positive fetus being diagnosed as having has a massive HFM only three days after delivery. Giving the mother the standard dose of Anti-D immunoglobulin without a previous test to find out how serious the HFM was showed that we do not test for this normally. So it seems to us necessary when considering prophylaxis of rhesus D immunisation to go back to first principles and carry out Kleihauer's test particularly when neonatal anaemia is found in the child.

The use of viral culture and p24 antigen testing to diagnose human immunodeficiency virus infection in neonates. The HIV Infection in Newborns French Collaborative Study Group.

BACKGROUND: Early diagnosis of human immunodeficiency virus (HIV) infection in infants born to infected mothers is important for the infants' medical care, but the presence of maternal antibodies makes serologic tests uninformative. METHODS: In a cohort study of 181 infants born to HIV-infected mothers, we assessed the diagnostic value of HIV viral culture and testing for the presence of p24 antigen. The infants were tested at birth, again during the first 3 months, then followed and tested at the age of at least 18 months. RESULTS: Of the 181 infants, 3 died of HIV infection and 37 were seropositive after the age of 18 months. Viral cultures at birth were positive in 19 of the 40 infected infants and in none of the uninfected infants, yielding a sensitivity of 48 percent (95 percent confidence interval, 32 to 63 percent) and a specificity of 100 percent (95 percent confidence interval, 97 to 100 percent). By the age of three months, 30 of the 40 infants (75 percent) had positive cultures; again, there were no false positive results among the infants who were tested a second time, of the 141 who remained uninfected. The sensitivity of testing for p24 antigen at birth was only 18 percent, with a specificity of 100 percent. The presence of p24 antigen at birth was associated with the development of early and severe HIV-related disease (P less than 0.04). CONCLUSIONS: Viral culture at birth can correctly identify about half of newborns with HIV infection. The fact that this usually sensitive technique fails to identify about half the ultimately infected neonates suggests that vertical transmission of HIV may occur late in pregnancy or during delivery.

[Neonatal digestive implantation of streptococcus group B. Influence of antibiotic therapy]. / Implantation digestive néonatale du streptocoque B. Influence de l'antibiothérapie.

Group B streptococcus (GBS) is an important cause of neonatal infection. Early-onset diseases are due to perinatal contamination. The epidemiology of late-onset infections is poorly known. Maternal colonization may be responsible for some of them. The relationships between neonatal colonization and late disease could be a colonization of the gut. The purpose of this 3 year-prospective study was to analyse the kinetics of gut colonization in neonates and the influence of antibiotherapy. One hundred and nineteen infants less than one month of age were included because of the presence of GBS in their gastric aspirates or GBS infection. Depending on the therapeutic strategy, the infants were separated into 3 groups: 1) amoxicillin plus aminoside greater than or equal to 10 days because of neonatal infection (28 infants), 2) same combination less than or equal to 5 days because a GBS infection was suspected but not confirmed (17 infants), 3) no antibiotics (77 infants). Fecal flora was regularly analysed by differential count. Antibiotics caused rapid disappearance of GBS from the gut. However, the same strain reappeared after stopping the antibiotics at a rate of 13.5%. Without antibiotics, GBS was implanted in 33% of cases. This difference of implantation rate is statistically significant (p less than 0.05). No GBS infection was observed in any infant after a follow-up examination of 6 months to 2 years. Among the clinical and bacteriological factors studied, adhesion only was correlated with the GBS implantation. These results allow to discuss therapeutic abstention in colonized infants without any signs of infection.

Frequency of the polymorphonuclear neutrophil Fc gamma receptor III deficiency in the French population and its involvement in the development of neonatal alloimmune neutropenia.

We report the case of a healthy woman (K.M.) who, after multiple pregnancies, developed an antibody directed against a nonpolymorphic region of the polymorphonuclear neutrophil (PMN) Fc gamma receptor III (FcRIII-CD16), which caused transient neonatal alloimmune neutropenia (NAIN). The antigenic target of the antibody was determined by an immunoprecipitation procedure and by phenotyping the mother's PMN. These latter did not react with monoclonal CD16 or polyclonal and monoclonal NA1 and NA2 antibodies, demonstrating the absence of PMN-FcRIII and, consequently, the NA-null phenotype. We also determined the frequency of the NA-null phenotype in a healthy, white population. Among 3,377 random blood donors, only four (in addition to K.M.) were PMN-FcRIII-deficient. These five individuals were healthy and only one (K.M.) presented an allo-CD16 antibody. The gene frequency of the NA-null phenotype was calculated as 0.0274 +/- 0.0059. We conclude that PMN-FcRIII deficiency is a rare phenomenon that can lead to CD16 alloimmunization and thus cause NAIN.

[Epidemiology and prevention of perinatal group B streptococcal infections]. / Epidémiologie et prévention des infections périnatales à streptocoque du groupe B.

Neonatal group B streptococcal infection is frequent and may be responsible for lethal neonatal septicaemia. Its preventive treatment is still hotly debated. Digestive and genital tracts colonization is frequent in mother (15-20% of the cases) but it is unstable. About one out of two infants born of a colonized woman becomes colonized or infected. Neonates can also be colonized during their stay in maternity hospitals. Colonization is much more frequent than infection which strikes 0.2 to 0.6 per cent of neonates (at a very early period in two-thirds of the cases), but it jeopardizes their prognosis for life and later their functional prognosis. Prematurity and chorioamnionitis are the two main infection facilitating factors. Some of the various measures proposed to prevent infection in neonates, such as antibiotic therapy of colonized mothers during pregnancy and of symptomatic colonized neonates, do not seem to be effective, but others are interesting, including administration of antibiotics to mothers during delivery in high-risk situations, combined with early detection and immediate bactericidal treatment of neonatal infections.