Real Time Central Assessment of Kidney Transplant Indication Biopsies by Microarrays: The INTERCOMEX Study.

The authors conducted a prospective trial to assess the feasibility of real time central molecular assessment of kidney transplant biopsy samples from 10 North American or European centers. Biopsy samples taken 1 day to 34 years posttransplantation were stabilized in RNAlater, sent via courier overnight at ambient temperature to the central laboratory, and processed (29 h workflow) using microarrays to assess T cell- and antibody-mediated rejection (TCMR and ABMR, respectively). Of 538 biopsy samples submitted, 519 (96%) were sufficient for microarray analysis (average length, 3 mm). Automated reports were generated without knowledge of histology and HLA antibody, with diagnoses assigned based on Molecular Microscope Diagnostic System (MMDx) classifier algorithms and signed out by one observer. Agreement between MMDx and histology (balanced accuracy) was 77% for TCMR, 77% for ABMR, and 76% for no rejection. A classification tree derived to provide automated sign-outs predicted the observer sign-outs with >90% accuracy. In 451 biopsy samples where feedback was obtained, clinicians indicated that MMDx more frequently agreed with clinical judgment (87%) than did histology (80%) (p = 0.0042). In 81% of feedback forms, clinicians reported that MMDx increased confidence in management compared with conventional assessment alone. The authors conclude that real time central molecular assessment is feasible and offers a useful new dimension in biopsy interpretation. ClinicalTrials.gov NCT#01299168.

C1 Inhibitor in Acute Antibody-Mediated Rejection Nonresponsive to Conventional Therapy in Kidney Transplant Recipients: A Pilot Study.

Complement inhibitors have not been thoroughly evaluated in the treatment of acute antibody-mediated rejection (ABMR). We performed a prospective, single-arm pilot study to investigate the potential effects and safety of C1 inhibitor (C1-INH) Berinert added to high-dose intravenous immunoglobulin (IVIG) for the treatment of acute ABMR that is nonresponsive to conventional therapy. Kidney recipients with nonresponsive active ABMR and acute allograft dysfunction were enrolled between April 2013 and July 2014 and received C1-INH and IVIG for 6 months (six patients). The primary end point was the change in eGFR at 6 months after inclusion (M+6). Secondary end points included the changes in histology and DSA characteristics and adverse events as evaluated at M+6. All patients showed an improvement in eGFR between inclusion and M+6: from 38.7 ± 17.9 to 45.2 ± 21.3 mL/min/1.73 m(2) (p = 0.0277). There was no change in histological features, except a decrease in the C4d deposition rate from 5/6 to 1/6 (p = 0.0455). There was a change in DSA C1q status from 6/6 to 1/6 positive (p = 0.0253). One deep venous thrombosis was observed. In a secondary analysis, C1-INH patients were compared with a similar historical control group (21 patients). C1-INH added to IVIG is safe and may improve allograft function in kidney recipients with nonresponsive acute ABMR.

[The school doctorand suspected child abuse : towards good practice recommendations in the child's interest]. / Le médecin scolaire et la suspicion de maltraitance à enfant : vers des recommandations de bonnes pratiques dans l'intérêt de l'enfant.

Child maltreatment, including all forms of mal¬treatment, remains a major public health problem in high-income countries. Healthcare professionals only contribute to a small proportion of reports. In French-speaking Belgium, almost 100 % of school-aged children are regularly submitted to periodical school health visits. The school health doctor is well placed to recognize neglected or abused children. Based on international good practice recommendations, this paper proposes means for the detection and management of child abuse in the context of school medicine.

La maltraitance infantile représente, dans les pays à haut niveau de revenus, un «problème de santé publique majeur¼, 5 à 10 % des enfants étant concernés, toutes formes de maltraitances confondues. Les professionnels de santé contribuent à une petite proportion seulement des signale¬ments. En Fédération Wallonie-Bruxelles, les bilans de santé scolaire périodiques couvrant près de 100 % des enfants sco¬larisés, le médecin scolaire est bien placé pour le repérage d'enfants exposés à une négligence de soins et/ou à de mauvais traitements. Se basant sur des recommandations de bonne pratique publiées, cet article propose des pistes d'action per¬mettant de contribuer à un meilleur repérage et à une prise en charge adaptée de la maltraitance infantile dans le cadre de la médecine scolaire.

[Combining microcredit, microinsurance, and the provision of health care can improve access to quality care in urban areas of Africa: Results of an experiment in the Bandalungwa health zone in Kinshasa, the Congo]. / Le couplage microcrédit/microassurance santé/offre de soins peut améliorer l'accessibilité aux soins de santé en milieu urbain africain Résultats d'une expérience menée dans la zone de santé de Bandalungwa à Kinshasa, Congo.

This study, based on a survey conducted in 2008, examines how combining microcredit, microinsurance, and health care provision can improve access to quality care in the health zone of Bandalungwa, in Kinshasa. The bivariate analysis showed a significant association between increased purchasing power and earnings (p = 0.001), between earnings and savings (p = 0.000), and between health insurance and improved access to health care. These results show that 68.8% of borrowers reported an increase in their purchasing power, of whom 82% reported profits. Those with savings were 24.7 times more likely to purchase health insurance than those without; and 72% of those who regularly made health insurance payments improved their access to care. Combining microcredit, health microinsurance, and health care can improve access to quality health care at lower cost. This suggests that health insurance could usefully be integrated into the primary health-care system.

[Early detection to prevent mental illness during adolescence: ethical and theoretical considerations]. / Détection prévenante en santé mentale chez l'adolescent: considérations éthiques et théoriques.

In the face of changes that characterise adolescence, a number of youth experience ill-being, as part of a normal developmental process. For some of them, however, this ill-being may represent early signs of a psychopathological process. Regarding depression and psychosis, such early signs are non-specific, which complicates and delays treatment. In addition, issues such as stigmatization and unfamiliarity with these psychopathologies represent major obstacles to treatment access. Attempts to early detection, which involves identifying risk factors in order to provide support and follow-up, making an effort to take these clinical signs seriously, while at the same time avoiding to mistake a normal developmental process for a pathological condition.

[Vulnerable children detected by the school health service: the forgotten?]. / Enfants en situation de vulnérabilité médico-psycho-sociale repérés par la médecine scolaire: les oubliés du réseau de soins?

The current health needs of children largely exceeds the biomedical model. The school doctor occupies a special position where he can take into account the social determinants of health and identify vulneirable children. After the detection by the school health service, the harmonious development of, the child requires that health professionals cooperate in a "preventive network".

Dual-polarization multi-band OFDM versus single-carrier DP-QPSK for 100 Gb/s long-haul WDM transmission over legacy infrastructure.

The transmission performance of coherent dual-polarization multi-band OFDM (DP-MB-OFDM) and QPSK (DP-QPSK) are experimentally compared for 100 Gb/s long-haul transport over legacy infrastructure combining G.652 fiber and 10 Gb/s WDM system. It is shown that DP-MB-OFDM and DP-QPSK have nearly the same performance at 100 Gb/s after transmission over a 10 × 100-km fiber line. Furthermore, the origin of performance degradations and limitations of the DP-MB-OFDM is explored numerically, as well as the impact of transmission distance and sub-band spacing.

Differential introgression from a sister species explains high F(ST) outlier loci within a mussel species.

Scanning genomes for loci with high levels of population differentiation has become a standard of population genetics. F(ST) outlier loci are most often interpreted as signatures of local selection, but outliers might arise for many other reasons too often left unexplored. Here, we tried to identify further the history and genetic basis underlying strong differentiation at F(ST) outlier loci in a marine mussel. A genome scan of genetic differentiation has been conducted between Atlantic and Mediterranean populations of Mytilus galloprovincialis. The differentiation was low overall (F(ST) = 0.03), but seven loci (2%) were strong F(ST) outliers. We then analysed DNA sequence polymorphism at two outlier loci. The genetic structure proved to be the consequence of differential introgression of alleles from the sister-hybridizing species Mytilus edulis. Surprisingly, the Mediterranean population was the most introgressed at these two loci, although the contact zone between the two species is nowadays localized along the Atlantic coasts of France and the British Isles. A historical contact between M. edulis and Mediterranean M. galloprovincialis should have happened during glacial periods. It proved difficult to disentangle two hypotheses: (i) introgression was adaptive, implying edulis alleles have been favoured in Mediterranean populations, or (ii) the genetic architecture of the barrier to edulis gene flow is different between the two M. galloprovincialis backgrounds. Five of the seven outliers between M. galloprovincialis populations were also outliers between M. edulis and Atlantic M. galloprovincialis, which would support the latter hypothesis. Differential introgression across semi-permeable barriers to gene flow is a neglected scenario to interpret outlying loci that may prove more widespread than anticipated.

How many times can parvovirus B19-related anemia recur in solid organ transplant recipients?

Parvovirus B19 (PB19) infection is known to cause acute erythroblastopenia-mediated anemia in solid organ transplant (SOT) recipients. Intravenous immunoglobulins (IVIg) and the decrease of immunosuppression level are supposed to induce a long-term remission, although no consensus exists about the dose and the schedule of IVIg administrations. However, a few reports have shown that PB19-related anemia can recur despite this treatment, with a maximum of 3 recurrences reported. In this report, we describe in detail the cases of 2 kidney recipients with PB19 infection. They experienced, respectively, 9 and 7 PB19-related anemia recurrences. Immunosuppression level was decreased and IVIg were administered at each recurrence followed by a transitory normalization of hemoglobin level and a decrease of serum PB19 viral load. Episodes were separated by several months. These patients raise an original therapeutic management question about a frequent viral infection in SOT recipients. One patient is currently receiving IVIg every 3 months as a secondary prophylaxis without recurrence to date. These 2 case reports are followed by a review of the literature.

First-generation versus third-generation comprehensive geriatric assessment instruments in the acute hospital setting: a comparison of the Minimum Geriatric Screening Tools (MGST) and the interRAI Acute Care (interRAI AC).

OBJECTIVE: Comparison of the first-generation Minimum Geriatric Screening Tools (MGST) and the third-generation interRAI Acute Care (interRAI AC). DESIGN: Based on a qualitative multiphase exchange of expert opinion, published evidence was critically analyzed and translated into a consensus. RESULTS: Both methods are intended for a multi-domain geriatric assessment in acute hospital settings, but each with a different scope and goal. MGST contains a collection of single-domain, internationally validated instruments. Assessment is usually triggered by care givers' clinical impression based on geriatric expertise. A limited selection of domains is usually assessed only once, by disciplines with domain-specific expertise. Clinical use results in improvement to screen geriatric problems. InterRAI AC, tailored for acute settings, intends to screen a large number of geriatric domains. Based on systematic observational data, risk domains are triggered and clinical guidelines are suggested. Multiple observation periods outline the evolution of patients' functioning over stay in comparison to the premorbid situation. The method is appropriate for application on geriatric and non-geriatric wards, filling geriatric knowledge gaps. The interRAI Suite contains a common set of standardized items across settings, facilitating data transfer in transitional care. CONCLUSION: The third-generation interRAI AC has advantages compared to the first-generation MGST. A cascade system is proposed to integrate both, complementary methods in practice. The systematic interRAI AC assessment detects risk domains. Subsequently, clinical protocols suggest components of the MGST as additional assessment. This cascade approach unites the strength of exhaustive assessment of the interRAI AC with domain-specific tools of the MGST.

[The "choking game" and asphyxial games: epidemiological and clinical data]. / Le "jeu du foulard" et autres jeux d'asphyxie: données épidémiologiques et cliniques.

Asphyxial games have been played by children and adolescents for generations. What seems to be more recent is an increase in mortality linked to the increasing use of ligatures and "playing" the game alone, as reported by the media. This article summarizes the current epidemiological and clinical data on the subject.

[Economic management of health crises affecting production animals in Europe]. / Instruments de gestion economique des crises sanitaires touchant les animaux de production en Europe.

The importance of animal health crises has considerably increased over the last few years. When a crisis occurs, farmers can receive financial support through various public, private and mixed compensation schemes. Economic losses resulting from diseases may be direct and indirect. If a disease is covered by European Union regulations then countries have a legal obligation to partly compensate farmers for direct losses, either directly through the national budget, or through a specific fund. The European Veterinary Fund also co-finances these losses. Only a few countries provide compensation for indirect losses. The private insurance sector also provides protection against some direct and indirect losses but the risks covered are variable. To encourage farmers to subscribe to this kind of insurance, some public authorities provide subsidies to help pay the premium. Insurance companies do not generally cover the risks linked to contagious diseases, but some companies do extend cover to include this type of risk. Several alternatives, such as mutual funds, are available to improve risk coverage. There is a lack of harmonisation among the various compensation schemes of different countries. Public authorities cannot provide full compensation, but mutual funds and private insurance companies are alternatives that should be further investigated and their use should be extended to other countries. A classification of diseases would harmonise the situation at the European level.

Phase-amplitude characterization of a high-repetition-rate quantum dash passively mode-locked laser.

We apply a novel phase-amplitude characterization method to a one-section quantum dash-based passively mode-locked laser at a 42.2 GHz repetition rate. The method relies on the measurement of the spectral phase of the longitudinal modes by the successive analysis of the correlation signal of a group of three adjacent modes. It provides both the temporal shape of the intensity and the phase of the emitted signal. A pulse of 1.5 ps of width is measured, and a pedestal is exhibited. Extinction ratio limitation is explained by investigating the origin of this pedestal. The accuracy of the method is estimated by comparing the measured autocorrelation signal and the calculated one from the phase analysis.

[Prevention of frailty in the elderly: a demographic challenge]. / Prévention de la vulnérabilité de la personne âgée: un défi démographique.

World population is ageing. This phenomenon is unprecedented, universal, long-lasting and has important implications. Unprecedented, because never before in human history, so many individuals have reached an advanced age. Universal, because all countries are now concerned. Long-lasting, because ageing started in the second half of the XXth century and will become even more pronounced over the XXIst century. With important implications, because it has and will have substantial consequences on human life and social composition. This article reviews quantitative data on ageing to appraise its extent and implication, the goal being to extend and stimulate the debate on ageing. International data are first presented, then analysis moves to Belgium estimates.

Health-related quality of life and cost of ambulatory care in osteoporosis: how may such outcome measures be valuable information to health decision makers and payers?

The objective was to quantify the outcome of osteoporosis (OP) in terms of health-related quality of life (HR-QOL) and cost of ambulatory care and to look at the association between these two outcomes variables. A cross-sectional health survey of 4800 Belgian individuals over the age of 45 years was used. Individuals having reported OP were retrieved and for each of them, at least two matched individuals for age, sex, residency location, and health insurance status were identified. All individuals were assessed with the SF-36. The two major health insurance providers furnished cost value for ambulatory care. HR-QOL and cost data were compared between the OP group and control group. Beta-coefficients from linear regression were calculated to give information on the relative importance of the association between each SF-36 dimensions and cost of ambulatory care. Of 4796 individuals appropriately surveyed, 221 (4.8%) reported OP. The control group included 651 individuals. The OP group experienced impaired HR-QOL compared to their matched counterparts, all the difference in mean or median SF-36 scores being significant at the level of P < 0.001. Osteoporotic respondents averaged 816 in cost of ambulatory care whereas controls averaged 579 (P < 0.001). When looking at detailed comparisons between categories of cost, costs in the OP group far exceeded those in the control group, all the differences being significant at the level of P < 0.001 except for home health nurse (P = 0.012). In the OP group, vitality dimensions played the most important role in the determination of cost (beta = -0.28, P < 0.001), followed by physical functioning (beta = -0.26, P < 0.01), general health, and social functioning (beta = -0.23, P < 0.01). This study evidences the burden of OP in terms of HR-QOL and cost of ambulatory care. Exploring the association between HR-QOL and cost show that mental dimension such as vitality can play an important role in the determination of cost. Conclusively, they should not be neglected in future management of OP.

Secular increase in the incidence of hip fractures in Belgium between 1984 and 1996: need for a concerted public health strategy.

OBJECTIVE: To determine the incidence of hip fractures (at the proximal end of the femur) in Belgium from 1984 to 1996. METHODS: Use was made of information from the national database on hospital bills, which fully covers the annual hospital stays in the whole of the country. FINDINGS: The mean annual incidence of hip fractures increased from 107.8 to 140.5 per 100,000 inhabitants between 1984 and 1996. The incidence of fractures of the femoral shaft (diaphysis), taken as a control, remained stable. The female to male ratio of these hip fractures was 2.3:1. Although the incidence by age group was identical for males and females, the fractures occurred approximately seven years earlier in women than in men. The demographic changes observed in Belgium during this period accounted for only 10% of the observed increase in the number of hip fractures. CONCLUSION: If no comprehensive preventive policy is set up promptly, there will be a sevenfold increase in the incidence of hip fractures between now and the year 2050 in Belgium.

Intensive and prolonged health promotion strategy may increase awareness of osteoporosis among postmenopausal women.

The aim of the study was to measure the results of a 15-year health promotion strategy towards osteoporosis, in an urban community of subjects over 45 years old, in terms of osteoporosis awareness and handling. To this end an ancillary study to a large survey of the Belgian population's self-perceived health status was carried out. A rectangular sample of 4800 individuals over 45 years old was randomly selected in two Belgian cities, among the affiliates of the two main health insurance providers. One of the cities (Liège) had been, since the early 1980s, the target of a constant health promotion strategy, directed to both the medical community and the general population, aimed at increasing osteoporosis awareness in women after the menopause. During the same period, no particular steps were taken in the other city (Aalst) to increase osteoporosis awareness in the community. In our study, the participants were asked to spontaneously report any chronic, serious and/or severe disorders that they had been suffering from, for at least 6 months, during the previous 12 months. They also provided a list of drugs they were taking at the time of the survey. Osteoporosis was reported to be a disease affecting 1.5% of men in Aalst and 1.3% of men in Liege (p = 0.61). For women, osteoporosis was reported to be present in 4.8% in Aalst and 10.8% in Liege (p<0.001). Self-reporting of osteoporosis prevalence in Liege was statistically significantly higher in women aged 45-64 years, 65-74 years or over 75 years (p<0.001). Obesity, alcohol consumption or physical activity were equally distributed between women from Liège and Aalst. Prescription drugs used for osteoporosis had been delivered to a similar proportion of men in Aalst and Liège. In women, a statistically significant difference in these prescription drugs was observed between Liège and Aalst, both for the overall population (p<0.001) and in each of the age classes (p<0.001 for 45-64 years and 65-74 years; p<0.009 for over 75 years). A continuous long-term health promotion strategy, directed toward both physicians and the general population, thus appears to increase awareness about osteoporosis in women over 45 years and/or in the medical community. This is reflected by an increase in self-reported prevalence of osteoporosis and in the prescription of drugs aimed at prevention and treatment of this disorder. Whether these observations reflect an appropriate diagnosis and a proper handling of the disease remains to be evaluated by objective diagnostic tools such as bone densitometry and by an evaluation of the effectiveness of prescription practices in postmenopausal women.

Promising new agents in osteoporosis.

Currently marketed inhibitors of bone resorption or stimulators of bone formation have significantly contributed to a better preventive and therapeutic approach to postmenopausal and senile osteoporosis. However, none of the available compounds has unequivocally demonstrated an ability to fully prevent the occurrence of new vertebral or peripheral osteoporotic fractures once the disease is established. Therefore, several new medications are being developed, with the aim of providing a better risk-benefit profile and/or a more favourable cost-utility assessment than available drugs. Potential inhibitors of bone resorption include specific inhibitors of the osteoclast's proton pump, inhibitors of prostaglandins or nitric oxide donors. Stimulators of osteoblastic activity and subsequent bone formation might be obtained by strontium salts, peptides of the parathyroid hormone family, growth hormone and insulin-like growth factors or bone morphogenetic proteins. Most of these compounds are now undergoing phase II/III development programmes, and results evaluating their potential benefit should be available within 1 to 5 years.

Direct costs of hip fractures in patients over 60 years of age in Belgium.

OBJECTIVE: Osteoporosis-related costs are now considered a major burden for health authorities in most developed countries. An accurate and exhaustive evaluation of these costs would be a major contribution to health economic studies evaluating the efficiency of screening and prevention strategies. Osteoporosis is the most frequent underlying cause of femoral neck fractures in the elderly; these fractures weigh heavily on healthcare budgets. However, in Belgium, very few data on the financial burden of hip fractures are available and no updated estimates have been made. The goal of this paper is to estimate the direct medical expenditures associated with hip fractures in Belgium in 1996. DESIGN AND SETTING: This 1-year population-based cross-sectional study is conducted from the social security perspective. The target population in this study are men and women aged 60 years and over. PATIENTS AND PARTICIPANTS: We selected patients who had been hospitalised for a hip fracture during the year 1996 who were also affiliated with a registered social security organisation (covering 25% of the Belgian population). The sample constituted 2374 patients. INTERVENTIONS: For each of these patients, we collected an exhaustive and detailed list of healthcare resource use as well as nursing home admissions following the hip fracture event. Cost items investigated in the analysis were inpatient hospital costs and outpatient costs. Mean annual costs per case recorded in the sample were then extrapolated to the whole country on the basis of an exhaustive list of diagnoses having lead to all countrywide hospitalisations (1,700,000 hospital stays/year). MAIN OUTCOME MEASURES AND RESULTS: The mean hospital inpatient costs for hip fracture were evaluated at 332,148 Belgian francs (BeF) [$US8977] per case and BeF4,367,746,200 ($US118,047,194) for the whole country (10 million inhabitants). Patients with a hip fracture experienced an annual BeF27,825 ($US752) extra outpatient cost during the year following this fracture event, after correcting for costs related to additional comorbidity already present before the hip fracture. Finally, after a proximal femoral neck fracture, the rate of nursing home admission was higher, both for men and women at any age compared with age- and gender-matched population. CONCLUSIONS: With a total cost (acute hospital and outpatient costs) of BeF4,667,894,950 ($US126,159,323) per year in Belgium, proximal femoral neck fracture should be considered a major health economic problem and appropriate measures to prevent this disease should be rapidly undertaken.