[Therapeutic adherence among asthma patients: Variations according to age groups. How can it be improved? The potential contributions of new technologies]. / Observance thérapeutique dans l'asthme : variation selon les classes d'âge. Comment l'améliorer ? Apport des nouvelles technologies.

While asthma patients' treatment adherence (TA) generally leaves to be desired, few data exist on TA evolution from age group to another. During the meeting of a working group of pneumo-pediatricians and adult pulmonologists, we reviewed the literature on adherence according to age group, examined explanations for poor adherence, and explored ways of improving adherence via new technologies. Asthma is a chronic disease for which TA is particularly low, especially during adolescence, but also among adults. Inhaled medications are the least effectively taken. Several explanations have been put forward: cost and complexity of treatments, difficulties using inhalation devices, poor understanding of their benefits, erroneous beliefs and underestimation of the severity of a fluctuating disease, fear of side effects, neglect, and denial (especially among teenagers). Poor TA is associated with risks of needless treatment escalation, aggravated asthma with frequent exacerbations, increased school absenteeism, degraded quality of life, and excessive mortality. Better compliance is based on satisfactory relationships between caregivers and asthmatics, improved caregiver training, and more efficient transmission to patients of relevant information. The recent evolution of innovative digital technologies opens the way for enhanced communication, via networks and dedicated applications, and thanks to connected inhalation devices, forgetfulness can be limited. Clinical research will also help to ameliorate TA. Lastly, it bears mentioning that analysis of the existing literature is hampered by differences in terms of working definitions and means of TA measurement.

[Community-acquired Staphylococcus aureus pneumonia]. / Pneumonie communautaire à staphylocoque doré.

We report a clinical case of a patient hospitalized for community-acquired Staphylococcus aureus pneumonia. A 26-year-old patient with no medical history went to the emergency department for fever. He quickly developed acute respiratory failure and community-acquired Staphylococcus aureus pneumonia as well as bacteremia were confirmed. This pulmonary infection is rare but can affect all age groups and occur in a variety of ways. Patients with community-acquired Staphylococcus aureus pneumonia have more severe clinical outcomes than those with community-acquired pneumonia caused by other germs. The article discusses the main characteristics of community-acquired Staphylococcus aureus pneumonia and recalls the recommendations in case of bacteremia with Staphylococcus aureus.

Nous rapportons le cas clinique d'un patient de 26 ans, sans antécédents médicaux, se présentant au service des urgences pour cause de fièvre persistante depuis plusieurs jours. Dans le décours de son admission à l'hôpital, le patient développe une insuffisance respiratoire aiguë d'installation rapide. Une pneumonie communautaire associée à une bactériémie à staphylocoque doré est alors mise en évidence. Les pneumonies communautaires à staphylocoque doré sont rares, mais peuvent toucher toutes les tranches d'âge et se présenter de façon variée. Leur sévérité est plus importante que celle des pneumonies communautaires imputées à d'autres germes. Par le biais de ce cas clinique, les principales caractéristiques des pneumonies communautaires à staphylocoque doré sont discutées et les recommandations médicales associées sont abordées.

Effects of a novel mobile health intervention compared to a multi-component behaviour changing program on body mass index, physical capacities and stress parameters in adolescents with obesity: a randomized controlled trial.

BACKGROUND: Less than 2% of overweight children and adolescents in Switzerland can participate in multi-component behaviour changing interventions (BCI), due to costs and lack of time. Stress often hinders positive health outcomes in youth with obesity. Digital health interventions, with fewer on-site visits, promise health care access in remote regions; however, evidence for their effectiveness is scarce. METHODS: This randomized controlled not blinded trial (1:1) was conducted in a childhood obesity center in Switzerland. Forty-one youth aged 10-18 years with body mass index (BMI) > P.90 with risk factors or co-morbidities or BMI > P.97 were recruited. During 5.5 months, the PathMate2 group (PM) received daily conversational agent counselling via mobile app, combined with standardized counselling (4 on-site visits). Controls (CON) participated in a BCI (7 on-site visits). We compared the outcomes of both groups after 5.5 (T1) and 12 (T2) months. Primary outcome was reduction in BMI-SDS (BMI standard deviation score: BMI adjusted for age and sex). Secondary outcomes were changes in body fat and muscle mass (bioelectrical impedance analysis), waist-to-height ratio, physical capacities (modified Dordel-Koch-Test), blood pressure and pulse. Additionally, we hypothesized that less stressed children would lose more weight. Thus, children performed biofeedback relaxation exercises while stress parameters (plasma cortisol, stress questionnaires) were evaluated. RESULTS: At intervention start median BMI-SDS of all patients (18 PM, 13 CON) was 2.61 (obesity > + 2SD). BMI-SDS decreased significantly in CON at T1, but not at T2, and did not decrease in PM during the study. Muscle mass, strength and agility improved significantly in both groups at T2; only PM reduced significantly their body fat at T1 and T2. Average daily PM app usage rate was 71.5%. Cortisol serum levels decreased significantly after biofeedback but with no association between stress parameters and BMI-SDS. No side effects were observed. CONCLUSIONS: Equally to BCI, PathMate2 intervention resulted in significant and lasting improvements of physical capacities and body composition, but not in sustained BMI-SDS decrease. This youth-appealing mobile health intervention provides an interesting approach for youth with obesity who have limited access to health care. Biofeedback reduces acute stress and could be an innovative adjunct to usual care.

[Paraneoplastic neurological syndromes]. / Les syndromes neurologiques paranéoplasiques.

Neurological paraneoplastic syndromes are non-metastatic complications of systemic cancers, often resulting from an immune response triggered by the crossed expression of neuronal antigens by tumour cells. Several neurological syndromes such as cerebellar degeneration, sensory neuronopathy, limbic encephalitis, encephalomyelitis or the Lambert-Eaton myasthenic syndrome are most often paraneoplastic and require prompt cancer screening, particularly if the patient shows risk factors for cancer. Although there are many exceptions to this rule, a given syndrome is often associated with a particular antibody and the corresponding tumour. A prompt diagnosis of neurological paraneoplastic syndrome is of major importance as it often reveals the underlying tumour. The treatment relies on both the elimination of the neoplasia and the control of the immune response.

Les syndromes neurologiques paranéoplasiques sont des complications neurologiques non métastatiques de cancers systémiques résultant, le plus souvent, d'une réaction immunitaire croisée dirigée contre des antigènes neuronaux membranaires ou intracellulaires. Certains de ces syndromes paranéoplasiques sont classiques comme les ataxies cérébelleuses, les neuronopathies sensitives ou ganglionopathies, l'encéphalite limbique, les encéphalomyélites ou le syndrome de Lambert-Eaton. Devant de tels tableaux cliniques, une étiologie paranéoplasique doit, surtout chez les patients présentant des facteurs de risque, être systématiquement recherchée. Bien que cette règle souffre de nombreuses exceptions, il y a souvent concordance entre un syndrome clinique spécifique, un type d'anticorps et une tumeur associée. Le diagnostic d'un syndrome neurologique paranéoplasique est essentiel puisqu'il révèle souvent le cancer sous-jacent. Le traitement comporte deux axes principaux : celui du cancer responsable et le contrôle de la réponse immunitaire.

Random telegraph signal analysis with a recurrent neural network.

We use an artificial neural network to analyze asymmetric noisy random telegraph signals, and extract underlying transition rates. We demonstrate that a long short-term memory neural network can outperform other methods, particularly for noisy signals and measurements with limited bandwidths. Our technique gives reliable results as the signal-to-noise ratio approaches one, and over a wide range of underlying transition rates. We apply our method to random telegraph signals generated by quasiparticle poisoning in a superconducting double dot, allowing us to extend our measurement of quasiparticle dynamics to new temperature regimes.

DCyFIR: a high-throughput CRISPR platform for multiplexed G protein-coupled receptor profiling and ligand discovery.

More than 800 G protein-coupled receptors (GPCRs) comprise the largest class of membrane receptors in humans. While there is ample biological understanding and many approved drugs for prototypic GPCRs, most GPCRs still lack well-defined biological ligands and drugs. Here, we report our efforts to tap the potential of understudied GPCRs by developing yeast-based technologies for high-throughput clustered regularly interspaced short palindromic repeats (CRISPR) engineering and GPCR ligand discovery. We refer to these technologies collectively as Dynamic Cyan Induction by Functional Integrated Receptors, or DCyFIR. A major advantage of DCyFIR is that GPCRs and other assay components are CRISPR-integrated directly into the yeast genome, making it possible to decode ligand specificity by profiling mixtures of GPCR-barcoded yeast strains in a single tube. To demonstrate the capabilities of DCyFIR, we engineered a yeast strain library of 30 human GPCRs and their 300 possible GPCR-Gα coupling combinations. Profiling of these 300 strains, using parallel (DCyFIRscreen) and multiplex (DCyFIRplex) DCyFIR modes, recapitulated known GPCR agonism with 100% accuracy, and identified unexpected interactions for the receptors ADRA2B, HCAR3, MTNR1A, S1PR1, and S1PR2. To demonstrate DCyFIR scalability, we profiled a library of 320 human metabolites and discovered several GPCR-metabolite interactions. Remarkably, many of these findings pertained to understudied pharmacologically dark receptors GPR4, GPR65, GPR68, and HCAR3. Experiments on select receptors in mammalian cells confirmed our yeast-based observations, including our discovery that kynurenic acid activates HCAR3 in addition to GPR35, its known receptor. Taken together, these findings demonstrate the power of DCyFIR for identifying ligand interactions with prototypic and understudied GPCRs.

The molecular chaperone sigma 1 receptor mediates rescue of retinal cone photoreceptor cells via modulation of NRF2.

Sigma 1 receptor (Sig1R), a putative molecular chaperone, has emerged as a novel therapeutic target for retinal degenerative disease. Earlier studies showed that activation of Sig1R via the high-affinity ligand (+)-pentazocine ((+)-PTZ) induced profound rescue of cone photoreceptor cells in the rd10 mouse model of retinitis pigmentosa; however the mechanism of rescue is unknown. Improved cone function in (+)-PTZ-treated mice was accompanied by reduced oxidative stress and normalization of levels of NRF2, a transcription factor that activates antioxidant response elements (AREs) of hundreds of cytoprotective genes. Here, we tested the hypothesis that modulation of NRF2 is central to Sig1R-mediated cone rescue. Activation of Sig1R in 661W cone cells using (+)-PTZ induced dose-dependent increases in NRF2-ARE binding activity and NRF2 gene/protein expression, whereas silencing Sig1R significantly decreased NRF2 protein levels and increased oxidative stress, although (+)-PTZ did not disrupt NRF2-KEAP1 binding. In vivo studies were conducted to investigate whether, in the absence of NRF2, activation of Sig1R rescues cones. (+)-PTZ was administered systemically for several weeks to rd10/nrf2+/+ and rd10/nrf2-/- mice. Through post-natal day 42, cone function was significant in rd10/nrf2+/+, but minimal in rd10/nrf2-/- mice as indicated by electroretinographic recordings using natural noise stimuli, optical coherence tomography and retinal histological analyses. Immunodetection of cones was limited in (+)-PTZ-treated rd10/nrf2-/-, though considerable in (+)-PTZ-treated rd10/nrf2+/+mice. The data suggest that Sig1R-mediated cone rescue requires NRF2 and provide evidence for a previously-unrecognized relationship between these proteins.

[Norovirus nosocomial outbreak : an hospital experience]. / Epidémie nosocomiale à norovirus : à propos d'une expérience hospitalière.

Human noroviruses (NoV) are the main pathogenic agents worldwide responsible for viral sporadic and epidemic gastroenteritis worldwide. A gastroenteritis outbreak broke out in patients hospitalized in several wards located in two different floors of a hospital in Liege, Belgium. The objective was to determine whether a same NoV strain would be involved in the two different floors, and to explore how this outbreak would have spread from a floor to the other. Stool samples from patients and healthcare workers were collected, as well as data from medical files. NoV detection, quantification and characterization were performed using molecular biology methods. A same NoV strain, from genotype GII.4, was detected in two patients hospitalized on the two different floors. This finding allowed to conclude that a same outbreak spread in the two floors, probably due to movements of common healthcare workers. A rapid NoV detection during outbreak is important in the aim to rapidly implement hygiene measures to limit the size of the outbreak.

Les norovirus humains (NoV) sont reconnus mondialement comme les principaux agents étiologiques de gastro-entérites virales sporadiques et épidémiques au niveau mondial. Une épidémie de gastro-entérites s'est déclarée chez des patients hospitalisés dans plusieurs salles d'un hôpital de la région liégeoise, situées à deux étages différents. L'objectif était de déterminer si une même souche de NoV était impliquée aux deux étages, et d'investiguer la manière dont l'épidémie se serait propagée d'un étage à l'autre. Des prélèvements ont été collectés chez les patients et le personnel soignant. Les dossiers médicaux ont été examinés. La détection, la quantification et la caractérisation des souches de NoV ont été réalisées par des méthodes de biologie moléculaire. Une même souche de NoV, du génotype GII.4, a été mise en évidence chez deux patients hospitalisés aux deux étages différents. Ce résultat indique qu'il s'agit de la même épidémie qui s'est étendue à deux étages, probablement transmise par l'intermédiaire du personnel soignant commun. L'identification précoce des NoV lors des épidémies est primordiale afin de mettre en place rapidement les mesures d'hygiène permettant de limiter leur propagation.

New insights into the phenotypes of atopic dermatitis linked with allergies and asthma in children: An overview.

Atopic dermatitis (AD) is a complex disease with multiple causes and complex mechanistic pathways according to age of onset, severity of the illness, ethnic modifiers, response to therapy and triggers. A group of difficult-to-manage patients characterized by early-onset AD and severe lifelong disease associated with allergic asthma and/or food allergy (FA) has been identified. In this study, we focus on these severe phenotypes, analysing their links with other atopic comorbidities, and taking into account the results from recent cohort studies and meta-analyses. The main hypothesis that is currently proposed to explain the onset of allergic diseases is an epithelial barrier defect. Thus, the atopic march could correspond to an epithelial dysfunction, self-sustained by a secondary allergenic sensitization, explaining the transition from AD to allergic asthma. Furthermore, AD severity seems to be a risk factor for associated FA. Results from population-based, birth and patient cohorts show that early-onset and severe AD, male gender, parental history of asthma, and early and multiple sensitizations are risk factors leading to the atopic march and the development of asthma. The importance of environmental factors should be recognized in these high-risk children and prevention programs adapted accordingly. Effective targeted therapies to restore both barrier function and to control inflammation are necessary; early emollient therapy is an important approach to prevent AD in high-risk children. Clinicians should also keep in mind the specific risk of atopic comorbidities in case of filaggrin loss-of-function mutations and the rare phenotypes of orphan syndromes due to heritable mutations in skin barrier components.

Knowledge, attitudes, representations and declared practices of nurses and physicians about obesity in a university hospital: training is essential.

In the context of a worldwide obesity epidemic, healthcare providers play a key role in obesity management. Knowledge of current guidelines and attitudes to prevent stigmatization are especially important. This study aimed to assess knowledge, attitudes, beliefs, perception of opportunity for intervention, declared practices and need for training and material of nurses and physicians about obesity in a Swiss University Hospital. A total of 834 physicians and nurses filled an online survey. The questionnaire was based on literature, exploratory interviews and expert committee review. It was pre-tested with 15 physicians and nurses. Participants declared a low level of negative attitudes towards individuals living with obesity. However, the results highlighted a lack of knowledge to diagnose obesity in adults and children, as well as confidence and training to care of patients with obesity. One-third of providers did not know how to calculate body mass index. Half of providers felt it was part of their role to take care of patients with obesity, even if 55% of them had the feeling that they did not have adequate training. Nurses and physicians working in a university hospital showed a low level of negative attitudes but a lack of knowledge and skills on obesity management. Training should be improved in this population to insure adequate and coherent messages and equal access to evidence-based treatment for patients living with obesity.

Visual outcomes and complications of cataract surgery with primary implantation in infants.

PURPOSE: To describe the visual results and postoperative complications of cataract surgery with primary intraocular lens (IOL) implantation performed in infants and to determine possible predictive factors related to poor visual outcome. METHODS: A retrospective consecutive case series of cataract surgeries with primary IOL implantation in infants was performed. Visual outcome and postoperative complications were recorded. A final visual acuity>0.5 logMAR was considered as a poor visual outcome. RESULTS: Sixty-one consecutive procedures were evaluated in 43 infants. Eighteen infants (42%) had bilateral cataract surgery and 25 (58%) had monocular surgery. The median age at primary surgery was 5.7 months (range: 4 weeks-24 months). The median follow-up was 47 months (range: 14-60 months). The median best-corrected visual acuity in logarithm of the minimum angle of resolution (logMAR) at the last follow-up examination was 1.00 in the case of unilateral surgery and 0.40 in the case of bilateral surgery. The overall visual result in all eyes was 0.50 logMAR. A better visual result was achieved when the infants were younger than 6 months or older than 12 months of age when surgery was performed. Opacification in the visual axis requiring secondary surgery occurred in 54% of the eyes (33/61). Postoperative inflammation occurred in 41% of the eyes (25/61) but was not associated with poor visual outcome (P=0.39). Glaucoma affected 11.5% of the eyes (7/61) and was significantly associated with poorer visual function (OR: 15.36, 95% CI 1.02-230.35, P=0.05). Compared with the unilateral cataract group, the OR of poor visual acuity was 0.06 (95% CI 0.01-0.35, P<0.01) in the bilateral cataract group. No statistical association was observed between final visual acuity>0.5 logMAR and leukocoria at time of diagnosis, IOL-related complications and postoperative strabismus. CONCLUSIONS: Primary IOL implantation is associated with an overall satisfactory visual outcome, especially when surgery is performed before 6 months or after 12 months of age and in bilateral cases. Glaucoma is the main complication associated with poor visual outcome.

Patients with ankylosing spondylitis have been breast fed less often than healthy controls: a case-control retrospective study.

OBJECTIVE: Ankylosing spondylitis (AS) is a chronic inflammatory disease affecting the spine and pelvis of young adults. On the HLA-B27 genetic background, the occurrence of AS is influenced by the intestinal microbiota. The goal of our study was to test whether breast feeding, which influences microbiota, can prevent the development of AS. METHODS: First, 203 patients with HLA-B27-positive AS fulfilling the modified New York criteria were recruited in the Department of Rheumatology, Ste Marguerite hospital in Marseilles. A total of 293 healthy siblings were also recruited to make up a control group within the same families. Second, 280 healthy controls, and 100 patients with rheumatoid arthritis and their siblings were recruited. The data collected were age, gender, number of brothers and sisters, age at disease onset, type and duration of feeding (breast or bottle). RESULTS: Patients with AS had been breast fed less often than healthy controls. In families where children were breast fed, the patients with AS were less often breast fed than their healthy siblings (57% vs 72%), giving an OR for AS onset of 0.53 (95% CI (0.36 to 0.77), p value=0.0009). Breast feeding reduced familial prevalence of AS. The frequency of breast feeding was similar in the AS siblings and in the 280 unrelated controls. However, patients with AS were less often breast fed compared with the 280 unrelated controls (OR 0.6, 95% CI (0.42 to 0.89), p<0.01). CONCLUSIONS: Our study suggests a breastfeeding-induced protective effect on the occurrence of AS. To our knowledge, this is the first study of breastfeeding history in patients with AS.

Inhibición del crecimiento longitudinal en hemiepifisiodesis: análisis experimental en conejos / Longitudinal growth inhibition in hemiepiphysiodesis: experimental analysis in rabbits

Introducción: La modificación del eje de un miembro mediante la detención parcial del crecimiento (hemiepifisiodesis), es un procedimiento habitual en la cirugía ortopédica pediátrica. Sin embargo no está bien establecido cuánto afecta este procedimiento al crecimiento final del hueso. El objetivo del presente trabajo fue determinar en forma experimental la inhibición del crecimiento longitudinal producido por una hemiepifisiodesis. Materiales y métodos: Se utilizaron, 10 conejos de 8 semanas de vida, a los que se les colocó una grapa en el fémur distal externo derecho. En la 8ª semana del estudio (16 semanas de vida) se realizó la comparación radiológica e histológica de ambos fémures. Resultados: La longitud final media de los fémures con grapas a las 8 semanas finalizado el experimento fue de 89,6mm (rango 87mm-95mm) versus 95,7mm (rango 91mm-100mm) de los fémures sanos. El porcentaje de inhibición media del crecimiento fisario al final del experimento fue de 6,58% (rango 3.2%-10%). Conclusiones: Se demostró experimentalmente la disminución global de la actividad de la fisis durante la hemiepifisiodesis. Esto debe ser tenido en cuenta cuando indicamos una hemiepifisiodesis unilateral en un niño con una discrepancia previa de longitud.

[Bronchopulmonary dysplasia-associated pulmonary arterial hypertension of very preterm infants]. / Hypertension artérielle pulmonaire des anciens grands prématurés bronchodysplasiques.

Bronchopulmonary dysplasia (BPD) of very preterm infants is a multifactorial chronic lung disease and its incidence has not decreased despite improvements in neonatal intensive care, including lung protective strategies. Pulmonary hypertension (PH) can complicate the course of BPD. Mortality in infants with BPD-associated PH is thought to be very high, but its incidence is unknown and a standard diagnostic and therapeutic strategy has not been well defined. In this article, we will first describe the current knowledge on the BPD-associated PH and the current treatments available for this pathology. We will then present the HTP-DBP Study, carried out in Paris (France) starting in 2012. The diagnosis of PH is suspected on echocardiographic criteria, but cardiac catheterization is considered the gold standard for diagnosis and evaluation of the severity of PH. Moreover, pulmonary vasoreactivity testing is used to guide the management of patients with PH. The pathogenesis of BPD-associated PH is poorly understood and even less is known about appropriate therapy. Today, optimizing ventilation and reducing the pulmonary vascular tone with specific pulmonary vasodilatator drugs are the main goals in treating HTP-associated DBP. Animal studies and a few clinical studies suggest that medications targeting the nitric oxide (NO) signaling pathway (NO inhalation, oral sildenafil citrate) could be effective treatments for BPD-associated PH, but they have not been approved for this indication. The HTP-DBP study is a French multicenter prospective observational study. The objective is to evaluate the frequency of BPD-associated PH, to describe its physiopathology, its severity (morbidity and mortality), and the effectiveness of current treatments.

The measurement of patients' expectations for health care: a review and psychometric testing of a measure of patients' expectations.

BACKGROUND: There is recognition of the importance of measuring patients' experiences, expectations and satisfaction. OBJECTIVES: To assess the literature on the concept and measurement of patients' expectations for health care, and to develop and test a measure of patients' expectations, using adult patients in community, general practice and hospital outpatient departments in Greater London, Norwich and Essex, UK. DATA SOURCES: Major electronic databases including the British Nursing Index, EMBASE, MEDLINE, PsycINFO and the Applied Social Sciences Index and Abstracts were searched between 2000 and 2009. REVIEW METHODS: Narrative review, semi-structured exploratory study and surveys of GP patients and hospital outpatients immediately before and after their surgery/clinic visit to measure their pre-visit expectations for their health care and their post-visit experiences (expectations met and satisfaction with visit) (site specific). RESULTS: A total of 20,439 titles and 266 abstracts were identified, of which 211 were included in the review. Most research designs were weak, with small or selected samples, and a theoretical frame of reference was rarely stated. The origin of questions about expectations was often absent, questions were frequently untested and those with reported reliability or validity data had generally mixed results. In the survey data the expectations measures met acceptability criteria for reliability; all exceeded the threshold of α = 0.70, in each mode of administration and sample type. Items and subscales also correlated at least moderately with those variables that they were expected to be associated with, supporting their validity. The item means within subscales were generally similar between samples and all-item-total correlations exceeded the acceptability threshold. Descriptive findings revealed that most patients ideally expected cleanliness, information about where to go, convenient and punctual appointments and helpful reception staff, the doctor to be knowledgeable, clear and easy to understand, to be involved in treatment decisions and to experience a reduction in symptoms/problems. Expectations least likely to be met included being seen on time and choice of hospital/doctor (items requested by the ethics committee). Other items that had low met expectations included helpfulness of reception staff, doctor being respectful and treating with dignity (hospital sample), doctor knowledgeable (hospital), being given reassurance, receiving advice about health/condition, information about cause and management of condition and information about benefits/side effects of treatment, being given an opportunity to discuss problems, and the three items on outcome expectancies. Previous consultations/experiences of health services and health-care staff/professionals most commonly influenced expectations. Overall, pre-visit realistic expectations were lower than patients' ideals or hopes. Most post-visit experiences indicated some unmet expectations (e.g. cause and management of health/condition, benefits/side effects of treatments) and some expectations that were exceeded. Generally, GP patients reported higher pre-visit expectations and post-visit met expectations. Correlations between subscale domains were strongest between the structure and process of health care, doctor-patient communication style and doctor's approach to giving information, all common indicators of the quality of health care, supporting the validity of the measures. The post-visit experiences subscale significantly predicted single-item summary ratings of overall met expectations and satisfaction. GP rather than hospital patients were also independently predictive of expectations met. Other predictors were having no/little anxiety/depression, older age (satisfaction) and fewer effects of health on quality of life (met expectations). LIMITATIONS: The surveys in clinics were based on convenience, not random sampling methods. CONCLUSIONS: These findings have implications for establishing the quality of health services and informing their improvement. Awareness of the patient's met and unmet expectations should enable staff to understand the patient's perspective and improve communication. This study examined the perspective of the patient only; it is not possible to examine the extent to which any expectations might have been unrealistically too high or too low. This is a challenge for future research. FUNDING: The National Institute for Health Research Health Technology Assessment programme and the National Co-ordinating Centre for Research Methodology (NCCRM).

Decreased bone turnover in children and adolescents with well controlled type 1 diabetes.

AIM: Osteoporosis is a common long-term complication of type 1 diabetes (T1DM). We aimed to determine whether bone mineral density (BMD) and turnover are already altered during childhood. PATIENTS AND METHODS: We recruited 27 T1DM children and 32 controls (age 10.5 +/- 2.5 yr.) and measured BMD (dual-energy x-ray absorptiometry); bone biomarkers levels (osteocalcin: OC; procollagen type 1 propeptides amino-terminal: PINP; crosslinking telopeptides of type 1 collagen C-terminal: CTX), glycated hemoglobin (HbA1c), dietary intake and physical activity. RESULTS: Patients with T1DM had lower levels of OC (70.3 +/- 3.3 vs 105.3 +/- 6.8), PINP (556.4 +/- 47.6 vs 716.3 +/- 53.8), CTX(0.97 +/- 0.07 vs 1.20 +/- 0.08), physical activity, and calcium intake. Biomarkers were negatively correlated with HbA1c. Though, BMD was similar among groups and not related to HbA1c, disease duration, physical activity or dietary intakes. CONCLUSIONS: Bone turnover is altered in T1DM children, whereas BMD remains normal during growth. Physical activity and optimal calcium intakes may improve bone metabolism and delay osteoporosis.

Dynamic changes in fetal microchimerism in maternal peripheral blood mononuclear cells, CD4+ and CD8+ cells in normal pregnancy.

OBJECTIVE: Cell trafficking during pregnancy results in persistence of small populations of fetal cells in the mother, known as fetal microchimerism (FMc). Changes in cell-free fetal DNA during gestation have been well described, however, less is known about dynamic changes in fetal immune cells in maternal blood. We have investigated FMc in maternal peripheral blood mononuclear cells (PBMC) longitudinally across gestation. STUDY DESIGN: Thirty-five women with normal pregnancies were studied. FMc was identified in PBMC, CD4+ and CD8+ subsets employing quantitative PCR assays targeting fetal-specific genetic polymorphisms. FMc quantities were reported as fetal genome equivalents (gEq) per 1,000,000 gEq mother's cells. Poisson regression modeled the rate of FMc detection. MAIN OUTCOME MEASURE: FMc in PBMC. RESULTS: The probability of detecting one fetal cell equivalent increased 6.2-fold each trimester [Incidence Rate Ratio (IRR) 95% CI: 1.73, 21.91; p = 0.005]. Although FMc in PBMC was not detected for the majority of time points, 7 of 35 women had detectable FMc during pregnancy at one or more time points, with the majority of positive samples being from the third trimester. There was a suggestion of greater HLA-sharing in families where women had FMc in PBMC. FMc was detected in 9% of CD4+ (2/23) and 18% of CD8+ (3/25) subsets. CONCLUSIONS: FMc in PBMC increased as gestation progressed and was found within CD4+ and CD8+ subsets in some women in the latter half of gestation. A number of factors could influence cellular FMc levels including sub-clinical fetal-maternal interface changes and events related to parturition. Whether FMc during pregnancy predicts persistent FMc and/or correlates with fetal-maternal HLA relationships also merits further study.