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[Development of a tool for the identification of socially vulnerable hospital patients].

OBJECTIVE: To develop and assess the metrological properties of a simple to use tool to identify socially vulnerable outpatients. METHODS: A multidisciplinary group of professionals selected five characteristics identifying social vulnerability, integrated in a self-reported questionnaire, from which 5 criteria identify the socially vulnerable outpatients consulting the hospital. The metrological performance of the tool was assessed on a sample of randomly selected outpatients admitted to the emergency department and the results referred to the independent assessment of two social workers. The sensitivity and specificity of the tool were determined and ROC curves drawn. RESULTS: 222 patients were included, aged from 15 to 93 Years (mean: 53 Years), 59% of whom were men. 78% filled out the questionnaire on their own, while 22% required help, usually for physical or material reasons and 87% answered the five questions without any difficulty. The kappa coefficient of agreement between the two social workers was estimated at 0.94 (CI: 0.89-0.98). The sensitivity of the self reported questionnaire was of 70% (CI: 64-76) and its specificity of 77% (CI: 71-82). The ROC curves showed that the modified tool had a sensitivity of 80% (Sp: 67%). With only 2 characteristics, this sensitivity was of 76% (Sp: 73%). CONCLUSION: This tool, which is based on the advice of various experts, is valid and presents acceptable metrological properties. Once some simplifications have been made, the questionnaire could be used in routine in any patient consulting the hospital because it is acceptable, simple to use and can be rapidly filled-in.

Academic Medical Centers↗

[Search for emboligenic heart disease in case of ischemic cerebral accidents].

The demonstration of a cardiac source of systemic embolism in patients who have suffered a cerebral ischemic event may have important therapeutic implications. This explains the large demand for echocardiography and Holter monitoring in these patients. The frequency of cerebral embolism of cardiac origin, the simplification of the diagnostic approach by non-invasive investigations and the precision of ultrasound techniques explains the tendency towards the indiscriminate generalisation of this attitude. However, the large number of potential patients for investigation, the limited facilities of investigation and the incertitude over the responsibility of certain cardiac abnormalities with respect to the context and age, are arguments in favour of a more selective investigative approach. The keystone of diagnosis is careful history taking and clinical examination with interpretation of the ECG and chest X-ray. Three clinical situations may then be identified: 1) A cardiac abnormality known to be highly embolic is diagnosed from the outset (e.g. mitral stenosis, valve prosthesis, endocarditis, myocardial infarction). The diagnostic work-up is no longer etiological: echocardiography may show intracardiac thrombi or a valvular vegetation, reinforcing the causal relationship, but the complementary investigations are mainly useful for evaluation the cardiac disease and for deciding on curative or preventive therapy. 2) A cardiac abnormality is diagnosed but its responsibility is doubtful due to its high prevalence and low embolic potential. This is the case of patients with mitral valve prolapse, mitral annular calcification, calcific aortic stenosis and VVI pacing. Complementary investigations are not discriminative for the etiological diagnosis of the cerebral embolism.(ABSTRACT TRUNCATED AT 250 WORDS)

Arrhythmias, Cardiac↗

Historical aspects of the dichotomy between manic-depressive disorders and schizophrenia.

The history of psychiatric classification is highly complex and this presentation must be restricted to a simplified overview. Guislain [Guislain, J., 1833. Traité des phrénopathies ou doctrine nouvelle des maladies mentales. Etablissement Encyclopédique, Brussels] and Zeller [Beil. Med. Corresp.-Bl. Würtemb. Arztl. Ver. 7 (1837) 321] established a unitarian concept of psychiatric disorder, permutations of which have survived until the present day. Kraepelin's [Kraepelin, E., 1899. Psychiatrie. Ein Lehrbuch für Studierende und Arzte (6th edn.). Johann Ambrosius Barth, Leipzig] dichotomy between "manic-depressive insanity" and dementia praecox was built mainly on Kahlbaum's [Kahlbaum, K., 1863. Die Gruppirung der Psychischen Krankheiten und die Eintheilung der Seelenstörungen. AW Kafemann, Danzig] classification, which took clinical symptoms, course and outcome into account. Kraepelin's well-accepted approach sought to provide a basis for diagnosis, prognosis, choice of treatment and causal research. Kraepelin's dichotomy came to be questioned on several grounds: (1) doubts about his unification of bipolar disorder [Gaz. Hôp. 24 (1851) 18] with melancholia, (2) doubts about the significance of Kraepelin's diagnostic groups for causal research [Z. Gesamte Neurol. Psychiatr. 12 (1912) 540], illustrated best by the work of Bonhoeffer [Bonhoefferm, K., 1912. Die symptomatischen Psychosen im Gefolge akuter Infektionen, Allgemeinerkrankungen und innerer Krankheiten. In: Aschaffenburg, G. (Ed.), Handbuch der Psychiatrie, 3. Abt., 1. Hälfte. Deuticke, Leipzig Wien], (3) the complex psychopathological descriptions and classifications of numerous subgroups of psychoses by Kleist [Monatsschr. Psychiatr. Neurol. 125 (1953) 526] and Leonhard [Leonhard, K., 1968. Aufteilung der endogenen Psychosen (4th edn.). Akademie Verlag, Berlin] and (4) description of the psychoses between affective and schizophrenic disorders (intermediate psychoses, mixed psychoses, schizo-affective psychoses) beginning with Kehrer and Kretschmer [Kehrer, F., Kretschmer, E., 1924. Die Veranlagung zu seelischen Störungen. (Monographien aus dem Gesamtgebiete der Neurologie 40) Springer, Berlin] and persisting up to the modern findings of a continuum between the two major groups of psychiatric disorders. Kraepelin's simplification has so far been more successful than the Kleist-Leonhard approach, but the modern and more descriptive trend in psychiatric classification favours the syndromal concept of Hoche and the concepts of continua between affective and schizophrenic disorders and between normal and pathological behaviour.

Bipolar Disorder↗

[Private accident insurance in Switzerland with reference to liability insurance as a part of social security].

On the Swiss market there exist various different accident insurance schemes and systems. Private accident insurance which is offered by the private insurers, date back to the middle of the 19th century. Since 1912 accident insurance is compulsory for all employees working in particularly dangerous industries, since 1984 it covers all employees in the country. In Switzerland there exists no general compulsory accident insurance. To perform as insurance carriers are qualified: private insurance companies, the Swiss Accident Insurance Company, and a number of the social health (sickness) insurers. Depending on the insurance system there are different approaches to renumerate the health costs. In the various social insurance systems the patient is rather free to chose his doctor and hospital (among those who have a contract with the insurer); in private insurance he is completely free. Yet the billing systems and the applicable rates and tarifs differ considerably. There are trends to simplify these systems and bring them more into mutual accordance. Due to the important rise of the health costs in Switzerland, there exists the danger that possible simplifications will bring about more public influence yet less private initiative and less incentives to really control costs without lessening the patients' possibilities.

Humans↗

Liquid-phase micro-extraction techniques in pesticide residue analysis.

Modern trends in analytical chemistry are towards the simplification and miniaturization of sample preparation, as well as the minimization of organic solvent used. In view of this aspect, several novel micro-extraction techniques are being developed in order to reduce the analysis step, increase the sample throughput and to improve the quality and the sensitivity of analytical methods. One of the emerging techniques in this area is liquid-phase micro-extraction (LPME). It is a miniaturized implementation of conventional liquid/liquid extraction (LLE) in which only microliters of solvents are used instead of several hundred milliliters in LLE. It is quick, inexpensive and can be automated. In the last few years, LPME has been combined with liquid chromatography (LC) and capillary electrophoresis (CE), besides the generally used coupling to gas chromatography (GC), and has been applied to various matrices, including biological, environmental, and food samples. This work is aimed at providing an overview of the major developments of LPME, coupled with chromatography and CE, as reported in the literature. The paper will focus on the application of the technique to different matrices and the aim is to reveal the panorama of opportunities and to try to indicate the potential of LPME in pesticide analysis. A critical review of the first applications to pesticide analyses is presented in the main part of the manuscript. The optimization of LPME as well as advantages and disadvantages are discussed. It is concluded that, because of its high pre-concentration factor, LPME can be introduced with benefit into water analysis for several pesticide groups. In particular, the application of LPME to non-polar pesticides in environmental analysis appears to be promising. However, similar to other micro-extraction techniques, such as solid phase micro-extraction (SPME), serious limitations still remain when analyzing semi-solid and solid environmental, food or biological matrices and/or highly polar compounds. Thus, other pre-concentration techniques may be a good alternative if an analytical problem cannot be sufficiently dealt with LPME.

Chromatography, Liquid↗

Determination of the quench velocity and rewetting temperature of hot surfaces: Formulation of a nonisothermal microscale hydrodynamic model.

A nonisothermal microscale model of the three-phase, solid-liquid-gas, contact zone is formulated in the context of rewetting phenomena. The model incorporates hydrodynamics, heat transfer, interfacial phenomena, and intermolecular long range forces, in a two-dimensional proximal region of the order of 1000 A in width and 100 A in thickness. The model comprises scaled mass, momentum, and energy balances, and their corresponding scaled boundary conditions. The small contact angles which are characteristic of rewetting situations facilitate the use of the lubrication approximation, and the dynamics of the liquid and gas phases is decoupled by applying the one-sided simplification. The microscale hydrodynamic model reflects the strong effect of the solid-liquid interactions on the film profile, and the attendant flow and thermal fields. Thinner films having smaller contact angles involve stronger solid-liquid attraction forces, and consequently they exhibit higher rewetting temperatures and lower evaporation and vapor recoil effects. Thermocapillary and evaporation and conduction effects are expressed by appropriate dimensionless numbers. A set of such numbers is defined in the context of the differential equations of the microscale model. This model covers the hydrodynamic aspect of rewetting phenomena, which are also controlled by thermodynamic and macroscale constraints. This calls for interfacing and appropriate combination between the microscale hydrodynamic model, thermodynamics, and other macroscale rewetting models, for the determination of rewetting temperatures and quench velocities of liquids on hot solid surfaces. This is addressed elsewhere, in subsequent papers that follow this work.

Journal Article↗

A continuum theory for the prediction of lateral and rotational positioning of alpha-helices in membrane proteins: bacteriorhodopsin.

We have developed a new method for the prediction of the lateral and the rotational positioning of transmembrane helices, based upon the present status of knowledge about the dominant interaction of the tertiary structure formation. The basic assumption about the interaction is that the interhelix binding is due to the polar interactions and that very short extramembrane loop segments restrict the relative position of the helices. Another assumption is made for the simplification of the prediction that a helix may be regarded as a continuum rod having polar interaction fields around it. The polar interaction field is calculated by a probe helix method, using a copolymer of serine and alanine as probe helices. The lateral position of helices is determined by the strength of the interhelix binding estimated from the polar interaction field together with the length of linking loop segments. The rotational positioning is determined by the polar interaction field, assuming the optimum lateral configuration. The structural change due to the binding of a prosthetic group is calculated, fixing the rotational freedom of a helix that is connected to the prosthetic group. Applying this method to bacteriorhodopsin, the optimum lateral and rotational positioning of transmembrane helices that are very similar to the experimental configuration was obtained. This method was implemented by a software system, which was developed for this work, and automatic calculation became possible for membrane proteins comprised of several transmembrane helices.

Amino Acid Sequence↗

[Procedures of therapeutic action in geriatric psychiatry (apropos of dementia states)].

In order to exist, geriatric psychiatry must have its roots in action to help the patients, the family and the caring staff. This approach to psychiatry must be directed both at the present situation of the patient and at the future of the disease. However, in order to act, one must introduce a meaning and a direction which become determined through action. In this context, the symptomatological approach is often hindered by a tendency to over-simplification and reductionism due to terminological flaws and to the inadequacy of its underlying rigid concepts. Such an approach is hindered also by the very nature of a type of medical practice, which establishes the observation of behaviours before making a therapeutic decision and starting treatment. Thus we can contrast two therapeutic procedures in relation to the dementias. On the one hand, a classical view which procedes from diagnosis to treatment. Its aim is to develop precise etiological and physiopathogenic references. Its objective is to eradicate disease and obtain a cure. On the other hand, another--contemporary and complementary--approach begins at the point of the patient's difficulties. These difficulties define the therapeutic aims, and from these, the appropriate symptomatology can be selected. This approach puts an emphasis on care and rehabilitation. It constantly throws back upon us the need to think about the quality of our work and allows us to avoid a clumsy use of the available resources. It provides the basis for the development of new alternative knowledge and introduces a new spirit into medicine from which demented patients will surely benefit.

Aged↗

The timing of antiparkinsonian treatment reduction after subthalamic nucleus stimulation.

The objective of this work was to precisely analyse the reduction of the antiparkinsonian treatment in 18 consecutive patients with Parkinson's disease (PD) operated on for bilateral subthalamic nucleus (STN) stimulation, first after 1 month of follow-up, then at 1 year postoperatively. Trihexyphenidyle, selegiline, entacapone, apomorphine and lisuride could be withdrawn shortly after starting STN electrical stimulation. The levodopa mean daily dose was reduced by 57% at 1 month after surgery and remained stable at 1 year. The mean ropinirole and bromocriptine daily dose decrements after surgery corresponded to 54 and 63%, respectively, at 1 month and to 77 and 40% at 1 year. At 12 months postoperatively, one third of the patients no longer received any antiparkinsonian drugs and the others were on monotherapy of either levodopa or dopamine agonists or received a combined treatment of a dopaminergic agonist and levodopa. In conclusion, STN stimulation allows a major reduction and simplification of antiparkinsonian treatment which can usually be achieved during the early postoperative period.

Aged↗

[Observational survey on the use of dual therapy in ocular hypertension or glaucoma treatment].

AIM: To ascertain why ophthalmologists shift therapy to a fixed-combination or non-fixed-combination drug therapy. PATIENTS AND METHODS: A prospective multicenter observational study was conducted among French ophthalmologists working in private or mixed practice. The study included adult patients with open-angle glaucoma or ocular hypertension, treated with monotherapy or dual therapy and needing to modify their initial treatment. The patients had to fill out a self-questionnaire 15 days after the change in therapy, evaluating the compliance and assessment of the new treatment. RESULTS: The analysis was made on 775 questionnaires filled out by ophthalmologists between March 1st and July 31st 2003 on 5734 patients. The mean age was 66.4+/-12.4 years and women represented 53.6% of the patients. The diagnosis had been made, on average, 7.5+/-7.3 years before. The mean initial intraocular pressure under treatment was 19.8+/-4.1 mmHg in both eyes. Initially, 58.2% of the patients had monotherapy, 40.4% dual therapy and 1.4% triple therapy. The main reasons for shifting therapy were "high intraocular pressure under treatment" for 63.5% of the patients and "simplification of the treatment" for 39.1% of the patients (several reasons per patient were accepted). Most of the patients were satisfied with their new therapy (71%), which in most cases was a fixed-combination therapy (95.2%). DISCUSSION: This study has shown that the use of at least two active principles is a common practice in the treatment of glaucoma and ocular hypertension. An additive therapy is given in order to better control the intraocular pressure, mainly with a fixed combination.

Adolescent↗

A simplified model for V-ATPase H+ extrusion.

An analytical model of V-type H+-translocating ATPase (V-ATPase) was developed based on an approximation to the mechanochemical model of Grabe et al. (Biophys. J., pp. 2798-2813, vol. 78, 2000). Grabe's work utilizes structural information and physiological assumptions to construct a detailed mechanochemical model of the V-ATPase. Due to the complexity of their model, it does not give a readily usable mathematical expression for the V-ATPase current. Based on their analysis of the structure of the proton pump, we develop a two-compartment model of the V-ATPase, which contains a membrane "half-channel" for proton translocation separated by a hydrophilic strip and a hydrophobic wall from the cytoplasm. Using the Langevin equation to describe proton transport across the membrane, we simplify the model based on their assumptions on the molecular structure of the pump and arrive at a general form of solution to the proton pump flux driven by ATP hydrolysis based on assumptions on the physiological properties of the strip and the wall, as well as the two fluid compartments. In this process of simplification, we explicitly relate V-ATPase structure, stoichiometry, pump efficiency, and ATP hydrolysis energy to the active pump current. The simplified model is used to provide model-generated approximations to measured data from a variety of laboratories. In addition, it provides a very compact characterization of V-ATPase, which can be used as a proton extruder in a variety of different cell membranes, as well as in the membranes of intracellular organelles. Index Terms-Electrophysiology, mechanochemstry, molecular motors, proton extrusion

Biological Transport, Active↗

Reduction and lumping of physiologically based pharmacokinetic models: prediction of the disposition of fentanyl and pethidine in humans by successively simplified models.

Physiologically based pharmacokinetic (PBPK) models can be used to predict drug disposition in humans from animal data and the influence of disease or other changes in physiology on the pharmacokinetics of a drug. The potential usefulness of a PBPK model must however be balanced against the considerable effort needed for its development. Proposed methods to simplify PBPK modeling include predicting the necessary tissue:blood partition coefficients (kp) from physicochemical data on the drug instead of determining them in vivo, formal lumping of model compartments, and replacing the various kp values of the organs and tissues by only two values, for "fat" and "lean" tissues, respectively. The aim of this study was to investigate the effects of simplifying complex PBPK models on their ability to predict drug disposition in humans. Arterial plasma concentration curves of fentanyl and pethidine were simulated by means of a number of successively reduced models. Median absolute prediction errors were used to evaluate the performance of each model, in relation to arterial plasma concentration data from clinical studies, and the Wilcoxon matched pairs test was used for comparison of predictions. An originally diffusion-limited model for fentanyl was simplified to perfusion-limitation, and this model was either lumped, reducing 11 organ/tissue compartments to six, or changed to a model based on only two kp values, those of fat (used for fat and lungs) and muscle (used for all other tissues). None of these simplifications appreciably changed the predictions of arterial drug concentrations in the 10 patients. Perfusion-limited models for pethidine were set up using either experimentally determined [Gabrielsson et al. 1986] or theoretically calculated [Davis and Mapleson 1993] kp values, and predictions using the former were found to be significantly better. Lumping of the models did not appreciably change the predictions; however, going from a full set of kp values to only two ("fat" and "lean") had an adverse effect. Using a kp for lungs determined either in rats or indirectly in humans [Persson et al. 1988], i.e., a total of three kp values, improved these predictions. In conclusion, this study strongly suggested that complex PBPK models for lipophilic basic drugs may be considerably reduced with marginal loss of power to predict standard plasma pharmacokinetics in humans. Determination of only two or three kp values instead of a "full" set can mean an important reduction of experimental work to define a basic model. Organs of particular pharmacological or toxicological interest should of course be investigated separately as needed. This study also suggests and applies a simple method for statistical evaluation of the predictions of PBPK models.

Adult↗

Low spatial-frequency channels in human vision: adaptation and masking.

Previous work showed that adapting to low spatial frequency gratings (below 1.5 cycles/degree) may cause maximal spatial adaptation at a significantly higher spatial frequency. It has been suggested that there are no adaptable spatial-frequency channels tuned to below 1.5 c/deg. Contrary to this view, we found that adaptation and masking with low spatial frequencies (0.12-1.0 c/deg) produced maximal threshold elevations when the test patterns were the same spatial frequency as the adapting or masking pattern. These results were obtained using test patterns that turned on and off gradually or sharply. The results suggest that there are form mechanisms optimally sensitive to very low spatial frequencies. Adaptation was selective to position (phase) and orientation at low spatial frequencies; masking was observed to be selective to orientation at a spatial frequency as low as 0.2 c/deg. A clear dichotomy between transient, motion channels and sustained, form channels at low spatial and temporal frequencies may represent an unrealistic simplification. There may exist directionally-selective motion mechanisms sensitive to very slow motion, and these may play a role in the discrimination of form. The discussion considers the bandwidths of the low spatial frequency mechanisms.

Adaptation, Ocular↗

[Simplification of on-line connection of analyzers and standardization problems].

On-line connection of automated analyzers to laboratory information system (LIS) reduces mistakes in inputing data for each samples. It also makes reporting faster in clinical laboratory. Moreover, connection of these instruments with sample transporting system enables analyses without touching samples directly. It, however, costs extremely high to construct such a system. It is because every automated analyzer uses different connecting protocol, so that we have to make a different program for each machine. For solving this problem, we have to make a standard for connecting protocol. It is very difficult to make a standard protocol fitting on all of the analyzers, considering its cost and other things. Furthermore, it must take a few decades to spreading the standard through the end users. ICCLS and NCCLS has been taking a central role for this problem since 1996, with a five-year plan to make an international standard. Until the standard will be laid, each clinical laboratories have to pay high costs to construct their systems, connecting different manufacturers' analyzers each other. Thus, we have developed a novel system which enables us to construct a laboratory automation system in a shorter time. For realizing this new system, we have reduced the number of connecting protocols for analyzers. Moreover, we have corrected the flow of laboratory works in order. Each programs are put together into a system as parts, or modules. This software system is now in operation in the clinical laboratory of Kochi Medical School. In this report, we describe the construction of this novel software system, and the effect obtained by using this system. Furthermore, we would show problems and things to be improved for making international standards for communication protocols between host and analyzing instruments.

Automation↗

Toxicity characterisation of organic contaminants in stormwaters from an agricultural headwater stream in south east England.

The transient movement of pesticides at biologically active concentrations during storm events is considered to be a cause of biological impoverishment in some headwater streams. The programme of work described sought to identify compounds that are the cause of toxic effects during such events. Along with targeted pesticide analysis, toxicity identification evaluation (TIE) procedures were used to identify compounds with a demonstrated toxic effect. These procedures were specifically directed towards isolating and attributing toxicity to classes of organic contaminants in samples collected from an English headwater stream during a storm event. The organic load was isolated by means of solid-phase extraction (SPE). Bioassay of the SPE extract at x 100 whole water concentrations confirmed that the samples contained substances toxic to Daphnia magna, although the raw samples were not toxic. Targeted pesticide analysis identified simazine and diuron as the major pesticides present and, using a toxicity unit (TU) approach. were shown to be responsible for a significant amount of the observed concentrate toxicity during a runoff event. However, they were not present in sufficient quantities to be totally responsible for a more toxic later event. By simplification of the SPE isolate using reverse-phase HPLC, fractions from which were tested for toxicity, the cause of concentrate toxicity in the later event was isolated to two discrete fractions. GC-MS analysis of these fractions identified nonylphenol. endosulfan sulphate and pendimethalin as present, with the majority of toxicity attributed to nonylphenol (NP). The main advantage of the TIE approach is that it allows biological active compounds with a demonstrated effect to be identified that may not be selected by more traditional techniques.

Agriculture↗

[Characteristics of the spatio-temporal organization of the P300 component of AEP during the "active" and "passive" stimulus perception in healthy subjects].

The concern of the work was in detection and analysis of P300 component of the acoustic evoked potential in healthy subjects in different experimental situations. During counting the rare sounds, P300 was most pronounced in the frontocentral and parietooccipital areas mainly of the left-hemisphere. The response shape was correlated with characteristics of the basic rhythm of the background EEG. Responses of simple and complex shapes were distinguished. The simplest responses were recorded in subjects with hypersynchronous alpha-rhythm. Analysis of three-dimensional dipole source localization showed that structures of the brainstem, limbic system, and frontal lobes participate in generation of the wave. In all the subjects, the decisive role in response generation was played by the brainstem structures. In persons with hypersynchronous alpha-rhythm, the contribution of the frontal lobes was less pronounced. During "passive" listening of sounds, P300 parameters significantly differed from those observed during counting only in 46% of cases (in persons having no hypersynchronous alpha-rhythm). A simplification of the response shape during "passive" listening was observed in these cases, the area of the maximal response expression was shifted to symmetrical areas of the right-hemisphere, the number of dipole sources reduced due to a decrease in the contribution of the frontal and limbic structures into the response generation.

Adolescent↗

[Typhoid fever in Amsterdam, 1991-2000, and the simplification of the national protocol for source and contact tracing].

OBJECTIVE: To determine the incidence of patients reported with typhoid fever in Amsterdam (1991-2000) and to evaluate the contact tracing for those patients with the specific objective of examining whether contact tracing can be simplified. DESIGN: Retrospective. METHOD: From an automated database, data were collected on all reported typhoid fever patients in Amsterdam during the period 1991-2000 and on their contact persons. RESULTS: One hundred and one patients with typhoid fever were reported during the study period, and Salmonella typhi infection was diagnosed in 12 of the 281 household contacts. For 96 of the 101 index patients, travelling abroad was the most likely source of infection. In 8 of the 12 contact persons with an S. typhi infection, the index person was the most likely source of infection, which is equivalent to a secondary transmission rate of 2.8% (8/277). Seven of the 8 secondary infected persons had symptoms indicative of typhoid fever infection and S. typhi was found in all their first stool samples. CONCLUSION: Supported by these results, the national guidelines for source and contact tracing in the case of typhoid fever have been amended. In the case of index patients with bad toilet hygiene or who are responsible for food preparation, the faeces of all household contacts must be examined once. If the contact persons have symptoms indicative of an S. typhi infection and/or if their work involves food preparation, their faeces should also be tested once. The changes to the national protocol will markedly reduce the labour-intensity of tracing and testing the contacts of patients with typhoid fever, thereby maintaining the quality of the process. Tracing the source of infection in the case of patients with typhoid fever will also remain important in the future in order to detect potential transmission within the Netherlands at an early stage.

Adolescent↗

Evaluation and simplification of the World Health Organization clinical case definition for paediatric AIDS.

The World Health Organization (WHO) clinical case definition for paediatric AIDS was tested during a 1-month period on 221 consecutive hospitalized children in Kigali, Rwanda. Relevant clinical features not included in the WHO case definition were also evaluated. Thirty-four out of the 221 children (15.4%) were HIV seropositive. Although the specificity of the WHO case definition was high (92%), the sensitivity and the positive predictive value (PPV) were low (41 and 48%, respectively). The following individual signs had a PPV at least equal to the complete WHO case definition: chronic diarrhoea (47%), respiratory distress secondary to lower respiratory tract infection (50%), oral candidiasis (53%), parotitis (67%), generalized lymphadenopathy (88%), and herpes zoster infection (100%). When logistic regression analysis was done on the nine variables included in the WHO case definition, confirmed maternal infection was the best predictive variable for HIV seropositivity in children (P less than 10(-5). We further excluded the serological status of the mother from the analysis and performed a stepwise logistic regression analysis on the 18 clinical signs and symptoms for which information had been collected. Those signs and symptoms contributing the most to the regression were: respiratory distress, chronic diarrhoea and generalized lymphadenopathy. Based on these findings, we propose a simplified clinical case definition for paediatric AIDS in Africa with better sensitivity, specificity and PPV than the WHO case definition. Further work is needed using this approach to develop case definitions useful for epidemiological surveillance and for case management.

Acquired Immunodeficiency Syndrome↗