Validation of candidate smear microscopy quality indicators, extracted from tuberculosis laboratory registers

SETTING: Kinshasa Province, Democratic Republic of Congo. OBJECTIVE: To identify and validate register-based indicators of acid-fast bacilli (AFB) microscopy quality. DESIGN: Selection of laboratories based on reliability and variation in routine smear rechecking results. Calculation of relative sensitivity (RS) compared to recheckers and its correlation coefficient (R) with candidate indicators based on a fully probabilistic analysis incorporating vague prior information using WinBUGS. RESULTS: The proportion of positive follow-up smears correlated well (median R 0.81, 95% credibility interval [CI] 0.58-0.93), and the proportion of first smear-positive cases fairly (median R 0.70, 95% CI 0.38-0.89) with RS. The proportions of both positive suspect and low positive case smears showed poor correlations (median R 0.27 and -0.22, respectively, with ranges including zero). CONCLUSIONS: The proportion of positives in follow-up smears is the most promising indicator of AFB smear sensitivity, while the proportion of positive suspects may be more indicative of accessibility and suspect selection. Both can be obtained from simple reports, and should be used for internal and external monitoring and as guidance for supervision. As proportion of low positive suspect smears and consistency within case series are more difficult to interpret, they should be used only on-site by laboratory professionals. All indicators require more research to define their optimal range in various settings.

Extracranial applications of diffusion-weighted magnetic resonance imaging

Diffusion-weighted MRI has become more and more popular in the last couple of years. It is already an accepted diagnostic tool for patients with acute stroke, but is more difficult to use for extracranial applications due to technical challenges mostly related to motion sensitivity and susceptibility variations (e.g., respiration and air-tissue boundaries). However, thanks to the newer technical developments, applications of body DW-MRI are starting to emerge. In this review, we aim to provide an overview of the current status of the published data on DW-MRI in extracranial applications. A short introduction to the physical background of this promising technique is provided, followed by the current status, subdivided into three main topics, the functional evaluation, tissue characterization and therapy monitoring.

Risk of adverse effects of intensified treatment in insulin-dependent diabetes mellitus: a meta-analysis

While the benefits of intensified insulin treatment in insulin-dependent (Type 1) diabetes mellitus (IDDM) are well recognized, the risks have not been comprehensively characterized. We examined the risk of severe hypoglycaemia, ketoacidosis, and death in a meta-analysis of randomized controlled trials. The MEDLINE database, reference lists, and specialist journals were searched electronically or by hand to identify relevant studies with at least 6 months of follow-up and the monitoring of glycaemia by glycosylated haemoglobin measurements. Logistic regression was used for calculation of combined odds ratios and 95% confidence intervals (95% CI). The influence of covariates was examined by including covariate-by-treatment interaction terms. Methodological study quality was assessed and sensitivity analyses were performed. Fourteen trials were identified. These contributed 16 comparisons with 1028 patients allocated to intensified and 1039 allocated to conventional treatment. A total of 846 patients suffered at least one episode of severe hypoglycaemia, 175 patients experienced ketoacidosis and 26 patients died. The combined odds ratio (95% CI) for hypoglycaemia was 2.99 (2.45-3.64), for ketoacidosis 1.74 (1.27-2.38) and for death from all causes 1.40 (0.65-3.01). The risk of severe hypoglycaemia was determined by the degree of normalization of glycaemia achieved (p=0.005 for interaction term), with the results from the Diabetes Control and Complications Trial (DCCT) in line with the other trials. Ketoacidosis risk depended on the type of intensified treatment used. Odds ratios (95% CI) were 7.20 (2.95-17.58) for exclusive use of pumps, 1.13 (0.15-8.35) for multiple daily injections and 1.28 (0.90-1.83) for trials offering a choice between the two (p = 0.004 for interaction). Mortality was significantly (p = 0.007) increased for causes potentially associated with acute complications (7 vs 0 deaths, 5 deaths attributed to ketoacidosis, and 2 sudden deaths), and non-significantly (p = 0.16) decreased for macrovascular causes (3 vs 8 deaths). We conclude that there is a substantial risk of severe adverse effects associated with intensified insulin treatment. Mortality from acute metabolic causes is increased; however, this is largely counterbalanced by a reduction in cardiovascular mortality. The excess of severe hypoglycemia in the DCCT is not exceptional. Multiple daily injection schemes may be safer than treatment with insulin pumps.

General laboratory diagnostics of eosinophilic GI diseases

Eosinophils and gastrointestinal tract interact in an intimate and enigmatic relationship. Under inflammatory conditions, eosinophil infiltration in the gastrointestinal tract is a common feature of numerous eosinophilic gastrointestinal disorders (EGIDs). EGIDs are disorders, for which the diagnosis is relatively difficult. Nevertheless, some common laboratory techniques are currently used for their diagnosis and disease monitoring. Besides eosinophils, mast cells and T cells have also been suggested to play a role in the pathogenesis of these disorders. Here, we review the pathogenesis and common laboratory approaches applied for their diagnosis, in particular eosinophil and mast cell markers.

Perioperative anaesthetic management of mediastinal mass in adults

Mediastinal mass syndrome remains an anaesthetic challenge that cannot be underestimated. Depending on the localization and the size of the mediastinal tumour, the clinical presentation is variable ranging from a complete lack of symptoms to severe cardiorespiratory problems. The administration of general anaesthesia can be associated with acute intraoperative or postoperative cardiorespiratory decompensation that may result in death due to tumour-related compression syndromes. The role of the anaesthesiologist, as a part of the interdisciplinary treatment team, is to ensure a safe perioperative period. However, there is still no structured protocol available for perioperative anaesthesiological procedure. The aim of this article is to summarize the genesis of and the diagnostic options for mediastinal mass syndrome and to provide a solid detailed methodology for its safe perioperative management based on a review of the latest literature and our own clinical experiences. Proper anaesthetic management of patients with mediastinal mass syndrome begins with an assessment of the preoperative status, directed foremost at establishing the localization of the tumour and on the basis of the clinical and radiological findings, discerning whether any vital mediastinal structures are affected. We have found it helpful to assign 'severity grade' (using a three-grade clinical classification scale: 'safe', 'uncertain', 'unsafe'), whereby each stage triggers appropriate action in terms of staffing and apparatus, such as the provision of alternatives for airway management, cardiopulmonary bypass and additional specialists. During the preoperative period, we are guided by a 12-point plan that also takes into account the special features of transportation into the operating theatre and patient monitoring. Tumour compression on the airways or the great vessels may create a critical respiratory and/or haemodynamic situation, and therefore the standard of intraoperative management includes induction of anaesthesia in the operating theatre on an adjustable surgical table, the use of short-acting anaesthetics, avoidance of muscle relaxants and maintenance of spontaneous respiration. In the case of severe clinical symptoms and large mediastinal tumours, we consider it absolutely essential to cannulate the femoral vessels preoperatively under local anaesthesia and to provide for the availability of cardiopulmonary bypass in the operating theatre, should extracorporeal circulation become necessary. The benefits of establishing vascular access under local anaesthesia clearly outweigh any associated degree of patient discomfort. In the case of patients classified as 'safe' or 'uncertain', a preoperative consensus with the surgeons should be reached as to the anaesthetic approach and the management of possible complications.

A standardized protocol for the prevention of clinically relevant venous air embolism during neurosurgical interventions in the semisitting position

OBJECTIVE: We report the results and complications associated with standardized intraoperative management designed for the prevention of hemodynamically relevant venous air embolism during surgery performed in the semisitting position. METHODS: A protocol for preoperative evaluation and intraoperative monitoring was developed and applied in 187 consecutive patients who underwent surgery in the semisitting position between 1999 and 2004. The protocol included preoperative transesophageal echocardiography examination (TEE), intraoperative TEE monitoring, catheterization of the right atrium and a combination of fluid input, positive end expiratory pressure, and standardized positioning aiming at a positive pressure in the transverse and sigmoid sinuses. Data were collected retrospectively from the charts and intraoperative anesthesiological protocols of the patients for the incidence of clinically relevant air embolism (i.e., TEE-diagnosed air embolism plus a decrease in end tidal CO2 or hemodynamic changes) and other complications related to the semisitting position. RESULTS: Three cases (1.6%) of relevant venous air embolism occurred in 187 patients. Only 1 case (0.5%) was hemodynamically relevant, with temporary arterial blood pressure decrease and heart rate increase. Pneumatocephalus leading to lethargy was a frequent postoperative finding, which resolved spontaneously in all except 1 patient with epileptic seizure and oculomotor nerve palsy attributable to space-occupying subdurally trapped air, which had to be treated surgically. There was no permanent morbidity or mortality related to the semisitting position. CONCLUSION: Fear of massive venous air embolism is one reason for dramatic decline in the use of the semisitting position in neurosurgical practice. We found that strict adherence to a standardized protocol using TEE monitoring before and during surgery; exclusion of patients with patent foramen ovale; and a combination of positive end expiratory pressure, fluid input, and a standardized position aiming a positive pressure in the transverse and sigmoid sinuses helped to greatly minimize this complication to a rate of 0.5% for hemodynamically relevant events.

Characterization of microfluidic systems with Doppler optical coherence tomography

Doppler Optical Coherence Tomography (DOCT) is a biomedical imaging technique that allows simultaneous structural imaging and flow monitoring inside biological tissues and materials with spatial resolution in the micrometer scale. It has recently been applied to the characterization of microfluidic systems. Structural and flow imaging of novel microfluidics platforms for cytotoxicologic applications were obtained with a real-time, Near Infrared Spectral Domain DOCT system. Characteristics such as flow homogeneity in the chamber, which is one of the most important parameters for cell culture, are investigated. OCT and DOCT images were used to monitor flow inside a specific platform that is based on microchannel division for a better flow homogeneity. In particular, the evolution of flow profile at the transition between the microchannel structure and the chamber is studied.

"Old proverbs in new skins – an fMRI study on defamiliarization"

We investigated how processing fluency and defamiliarization (the art of rendering familiar notions unfamiliar) contribute to the affective and esthetic processing of reading in an event-related functional magnetic-resonance-imaging experiment.We compared the neural correlates of processing (a) familiar German proverbs, (b) unfamiliar proverbs, (c) defamiliarized variations with altered content relative to the original proverb (proverb-variants), (d) defamiliarized versions with unexpected wording but the same content as the original proverb (proverb-substitutions), and (e) non-rhetorical sentences. Here, we demonstrate that defamiliarization is an effectiveway of guiding attention, but that the degree of affective involvement depends on the type of defamiliarization: enhanced activation in affect-related regions (orbito-frontal cortex, medPFC) was found only if defamiliarization altered the content of the original proverb. Defamiliarization on the level of wording was associated with attention processes and error monitoring. Although proverb-variants evoked activation in affect-related regions, familiar proverbs received the highest beauty ratings.

15 Years of Microstate Research in Schizophrenia - Where Are We? A Meta-Analysis

Schizophrenia patients show abnormalities in a broad range of task demands. Therefore, an explanation common to all these abnormalities has to be sought independently of any particular task, ideally in the brain dynamics before a task takes place or during resting state. For the neurobiological investigation of such baseline states, EEG microstate analysis is particularly well suited, because it identifies subsecond global states of stable connectivity patterns directly related to the recruitment of different types of information processing modes (e.g., integration of top-down and bottom-up information). Meanwhile, there is an accumulation of evidence that particular microstate networks are selectively affected in schizophrenia. To obtain an overall estimate of the effect size of these microstate abnormalities, we present a systematic meta-analysis over all studies available to date relating EEG microstates to schizophrenia. Results showed medium size effects for two classes of microstates, namely, a class labeled C that was found to be more frequent in schizophrenia and a class labeled D that was found to be shortened. These abnormalities may correspond to core symptoms of schizophrenia, e.g., insufficient reality testing and self-monitoring as during auditory verbal hallucinations. As interventional studies have shown that these microstate features may be systematically affected using antipsychotic drugs or neurofeedback interventions, these findings may help introducing novel diagnostic and treatment options.

Emergence of acquired HIV-1 drug resistance has almost been stopped in Switzerland - a 15 year prospective cohort analysis

BACKGROUND  Drug resistance is a major barrier to successful antiretroviral treatment (ART). Therefore, it is important to monitor time trends at a population level. METHODS  We included 11,084 ART-experienced patients from the Swiss HIV Cohort Study (SHCS) between 1999 and 2013. The SHCS is highly representative and includes 72% of patients receiving ART in Switzerland. Drug resistance was defined as the presence of at least one major mutation in a genotypic resistance test. To estimate the prevalence of drug resistance, data for patients with no resistance test was imputed based on patient's risk of harboring drug resistant viruses. RESULTS  The emergence of new drug resistance mutations declined dramatically from 401 to 23 patients between 1999 and 2013. The upper estimated prevalence limit of drug resistance among ART-experienced patients decreased from 57.0% in 1999 to 37.1% in 2013. The prevalence of three-class resistance decreased from 9.0% to 4.4% and was always <0.4% for patients who initiated ART after 2006. Most patients actively participating in the SHCS in 2013 with drug resistant viruses initiated ART before 1999 (59.8%). Nevertheless, in 2013, 94.5% of patients who initiated ART before 1999 had good remaining treatment options based on Stanford algorithm. CONCLUSION  HIV-1 drug resistance among ART-experienced patients in Switzerland is a well-controlled relic from the pre-combination ART era. Emergence of drug resistance can be virtually stopped with new potent therapies and close monitoring.