BIS monitoring versus clinical assessment for sedation in mechanically ventilated adults in the intensive care unit and its impact on clinical outcomes and resource utilization.

BACKGROUND: Patients admitted to intensive care and on mechanical ventilation, are administered sedative and analgesic drugs to improve both their comfort and interaction with the ventilator. Optimizing sedation practice may reduce mortality, improve patient comfort and reduce cost. Current practice is to use scales or scores to assess depth of sedation based on clinical criteria such as consciousness, understanding and response to commands. However these are perceived as subjective assessment tools. Bispectral index (BIS) monitors, which are based on the processing of electroencephalographic signals, may overcome the restraints of the sedation scales and provide a more reliable and consistent guidance for the titration of sedation depth.The benefits of BIS monitoring of patients under general anaesthesia for surgical procedures have already been confirmed by another Cochrane review. By undertaking a well-conducted systematic review our aim was to find out if BIS monitoring improves outcomes in mechanically ventilated adult intensive care unit (ICU) patients. OBJECTIVES: To assess the effects of BIS monitoring compared with clinical sedation assessment on ICU length of stay (LOS), duration of mechanical ventilation, any cause mortality, risk of ventilator-associated pneumonia (VAP), risk of adverse events (e.g. self-extubation, unplanned disconnection of indwelling catheters), hospital LOS, amount of sedative agents used, cost, longer-term functional outcomes and quality of life as reported by authors for mechanically ventilated adults in the ICU. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, CINAHL, ProQuest, OpenGrey and SciSearch up to May 2017 and checked references citation searching and contacted study authors to identify additional studies. We searched trial registries, which included clinicaltrials.gov and controlled-trials.com. SELECTION CRITERIA: We included all randomized controlled trials comparing BIS versus clinical assessment (CA) for the management of sedation in mechanically ventilated critically ill adults. DATA COLLECTION AND ANALYSIS: We used Cochrane's standard methodological procedures. We undertook analysis using Revman 5.3 software. MAIN RESULTS: We identified 4245 possible studies from the initial search. Of those studies, four studies (256 participants) met the inclusion criteria. One more study is awaiting classification. Studies were, conducted in single-centre surgical and mixed medical-surgical ICUs. BIS monitor was used to assess the level of sedation in the intervention arm in all the studies. In the control arm, the sedation assessment tools for CA included the Sedation-Agitation Scale (SAS), Ramsay Sedation Scale (RSS) or subjective CA utilizing traditional clinical signs (heart rate, blood pressure, conscious level and pupillary size). Only one study was classified as low risk of bias, the other three studies were classified as high risk.There was no evidence of a difference in one study (N = 50) that measured ICU LOS (Median (Interquartile Range IQR) 8 (4 to 14) in the CA group; 12 (6 to 18) in the BIS group; low-quality evidence).There was little or no effect on the duration of mechanical ventilation (MD -0.02 days (95% CI -0.13 to 0.09; 2 studies; N = 155; I2 = 0%; low-quality evidence)). Adverse events were reported in one study (N = 105) and the effects on restlessness after suction, endotracheal tube resistance, pain tolerance during sedation or delirium after extubation were uncertain due to very low-quality evidence. Clinically relevant adverse events such as self-extubation were not reported in any study. Three studies reported the amount of sedative agents used. We could not measure combined difference in the amount of sedative agents used because of different sedation protocols and sedative agents used in the studies. GRADE quality of evidence was very low. No study reported other secondary outcomes of interest for the review. AUTHORS' CONCLUSIONS: We found insufficient evidence about the effects of BIS monitoring for sedation in critically ill mechanically ventilated adults on clinical outcomes or resource utilization. The findings are uncertain due to the low- and very low-quality evidence derived from a limited number of studies

Hepatolithiasis with biliary ascariasis – a case report

BACKGROUND: Biliary ascariasis is regarded as possible etiological factor for hepatolithiasis. Here we report one case of a patient with hepatolithiasis with biliary ascariasis who developed a liver abscess, which was treated with partial hepatectomy. CASE PRESENTATION: A young adult female presented with epigastric pain and vomiting with repeated attacks of cholangitis. ERCP showed evidence of multiple intrahepatic calculi with the development of abscess in the left lobe of liver. The patient underwent partial hepatectomy and was found to have biliary ascariasis on histology. She was treated with antihelmenthic therapy and has had an uneventful postoperative period of 2 years. CONCLUSION: Biliary ascariasis with hepatolithiasis, although rare, should be considered in endemic countries

Malnutrition Has No Effect on the Timing of Human Tooth Formation

The effect of nutrition on the timing of human tooth formation is poorly understood. Delays and advancements in dental maturation have all been reported as well as no effect. We investigated the effect of severe malnutrition on the timing of human tooth formation in a large representative sample of North Sudanese children. The sample (1102 males, 1013 females) consisted of stratified randomly selected healthy individuals in Khartoum, Sudan, aged 2-22 years using a cross-sectional design following the STROBE statement. Nutritional status was defined using WHO criteria of height and weight. Body mass index Z-scores and height for age Z-scores of ≤-2 (cut-off) were used to identify the malnourished group (N = 474) while the normal was defined by Z-scores of ≥0 (N = 799). Clinical and radiographic examination of individuals, with known ages of birth was performed including height and weight measurements. Mandibular left permanent teeth were assessed using eight crown and seven root established tooth formation stages. Mean age at entry and mean age within tooth stages were calculated for each available tooth stage in each group and compared using a t-test. Results show the mean age at entry and mean age within tooth stages were not significantly different between groups affected by severe malnutrition and normal children (p>0.05). This remarkable finding was evident across the span of dental development. We demonstrate that there is little measurable effect of sustained malnutrition on the average timing of tooth formation. This noteworthy finding supports the notion that teeth have substantial biological stability and are insulated from extreme nutritional conditions compared to other maturing body systems

Recommendations for the design of therapeutic trials for neonatal seizures

Although seizures have a higher incidence in neonates than any other age group and are associated with significant mortality and neurodevelopmental disability, treatment is largely guided by physician preference and tradition, due to a lack of data from welldesigned clinical trials. There is increasing interest in conducting trials of novel drugs to treat neonatal seizures, but the unique characteristics of this disorder and patient population require special consideration with regard to trial design. The Critical Path Institute formed a global working group of experts and key stakeholders from academia, the pharmaceutical industry, regulatory agencies, neonatal nurse associations, and patient advocacy groups to develop consensus recommendations for design of clinical trials to treat neonatal seizures. The broad expertise and perspectives of this group were invaluable in developing recommendations addressing: (1) use of neonate-specific adaptive trial designs, (2) inclusion/exclusion criteria, (3) stratification and randomization, (4) statistical analysis, (5) safety monitoring, and (6) definitions of important outcomes. The guidelines are based on available literature and expert consensus, pharmacokinetic analyses, ethical considerations, and parental concerns. These recommendations will ultimately facilitate development of a Master Protocol and design of efficient and successful drug trials to improve the treatment and outcome for this highly vulnerable population

Ethnic differences in oral health and use of dental services:cross-sectional study using the 2009 Adult Dental Health Survey

Background Oral health impacts on general health and quality of life, and oral diseases are the most common non-communicable diseases worldwide. Non-White ethnic groups account for an increasing proportion of the UK population. This study explores whether there are ethnic differences in oral health and whether these are explained by differences in sociodemographic or lifestyle factors, or use of dental services. Methods We used the Adult Dental Health Survey 2009 to conduct a cross-sectional study of the adult general population in England, Wales and Northern Ireland. Ethnic groups were compared in terms of oral health, lifestyle and use of dental services. Logistic regression analyses were used to determine whether ethnic differences in fillings, extractions and missing teeth persisted after adjustment for potential sociodemographic confounders and whether they were explained by lifestyle or dental service mediators. Results The study comprised 10,435 (94.6 %) White, 272 (2.5 %) Indian, 165 (1.5 %) Pakistani/Bangladeshi and 187 (1.7 %) Black participants. After adjusting for confounders, South Asian participants were significantly less likely, than White, to have fillings (Indian adjusted OR 0.25, 95 % CI 0.17-0.37; Pakistani/Bangladeshi adjusted OR 0.43, 95 % CI 0.26-0.69), dental extractions (Indian adjusted OR 0.33, 95 % CI 0.23-0.47; Pakistani/Bangladeshi adjusted OR 0.41, 95 % CI 0.26-0.63), and <20 teeth (Indian adjusted OR 0.31, 95 % CI 0.16-0.59; Pakistani/Bangladeshi adjusted OR 0.22, 95 % CI 0.08-0.57). They attended the dentist less frequently and were more likely to add sugar to hot drinks, but were significantly less likely to consume sweets and cakes. Adjustment for these attenuated the differences but they remained significant. Black participants had reduced risk of all outcomes but after adjustment for lifestyle the difference in fillings was attenuated, and extractions and tooth loss became non-significant. Conclusions Contrary to most health inequalities, oral health was better among non-White groups, in spite of lower use of dental services. The differences could be partially explained by reported differences in dietary sugar

The Uptake of Integrated Perinatal Prevention of Mother-to-Child HIV Transmission Programs in Low- and Middle-Income Countries: A Systematic Review

BACKGROUND: The objective of this review was to assess the uptake of WHO recommended integrated perinatal prevention of mother-to-child transmission (PMTCT) of HIV interventions in low- and middle-income countries. METHODS AND FINDINGS: We searched 21 databases for observational studies presenting uptake of integrated PMTCT programs in low- and middle-income countries. Forty-one studies on programs implemented between 1997 and 2006, met inclusion criteria. The proportion of women attending antenatal care who were counseled and who were tested was high; 96% (range 30-100%) and 81% (range 26-100%), respectively. However, the overall median proportion of HIV positive women provided with antiretroviral prophylaxis in antenatal care and attending labor ward was 55% (range 22-99%) and 60% (range 19-100%), respectively. The proportion of women with unknown HIV status, tested for HIV at labor ward was 70%. Overall, 79% (range 44-100%) of infants were tested for HIV and 11% (range 3-18%) of them were HIV positive. We designed two PMTCT cascades using studies with outcomes for all perinatal PMTCT interventions which showed that an estimated 22% of all HIV positive women attending antenatal care and 11% of all HIV positive women delivering at labor ward were not notified about their HIV status and did not participate in PMTCT program. Only 17% of HIV positive antenatal care attendees and their infants are known to have taken antiretroviral prophylaxis. CONCLUSION: The existing evidence provides information only about the initial PMTCT programs which were based on the old WHO PMTCT guidelines. The uptake of counseling and HIV testing among pregnant women attending antenatal care was high, but their retention in PMTCT programs was low. The majority of women in the included studies did not receive ARV prophylaxis in antenatal care; nor did they attend labor ward. More studies evaluating the uptake in current PMTCT programs are urgently needed

In vivo biomolecular imaging of zebrafish embryos using confocal Raman spectroscopy

Zebrafish embryos provide a unique opportunity to visualize complex biological processes, yet conventional imaging modalities are unable to access intricate biomolecular information without compromising the integrity of the embryos. Here, we report the use of confocal Raman spectroscopic imaging for the visualization and multivariate analysis of biomolecular information extracted from unlabeled zebrafish embryos. We outline broad applications of this method in: (i) visualizing the biomolecular distribution of whole embryos in three dimensions, (ii) resolving anatomical features at subcellular spatial resolution, (iii) biomolecular profiling and discrimination of wild type and ΔRD1 mutant Mycobacterium marinum strains in a zebrafish embryo model of tuberculosis and (iv) in vivo temporal monitoring of the wound response in living zebrafish embryos. Overall, this study demonstrates the application of confocal Raman spectroscopic imaging for the comparative bimolecular analysis of fully intact and living zebrafish embryos

Optimizing the procedure of grain nutrient predictions in barley via hyperspectral imaging

Hyperspectral imaging enables researchers and plant breeders to analyze various traits of interest like nutritional value in high throughput. In order to achieve this, the optimal design of a reliable calibration model, linking the measured spectra with the investigated traits, is necessary. In the present study we investigated the impact of different regression models, calibration set sizes and calibration set compositions on prediction performance. For this purpose, we analyzed concentrations of six globally relevant grain nutrients of the wild barley population HEB-YIELD as case study. The data comprised 1,593 plots, grown in 2015 and 2016 at the locations Dundee and Halle, which have been entirely analyzed through traditional laboratory methods and hyperspectral imaging. The results indicated that a linear regression model based on partial least squares outperformed neural networks in this particular data modelling task. There existed a positive relationship between the number of samples in a calibration model and prediction performance, with a local optimum at a calibration set size of ~40% of the total data. The inclusion of samples from several years and locations could clearly improve the predictions of the investigated nutrient traits at small calibration set sizes. It should be stated that the expansion of calibration models with additional samples is only useful as long as they are able to increase trait variability. Models obtained in a certain environment were only to a limited extent transferable to other environments. They should therefore be successively upgraded with new calibration data to enable a reliable prediction of the desired traits. The presented results will assist the design and conceptualization of future hyperspectral imaging projects in order to achieve reliable predictions. It will in general help to establish practical applications of hyperspectral imaging systems, for instance in plant breeding concepts

Comparative costs and activity from a sample of UK clinical trials units

Background: The costs of medical research are a concern. Clinical Trials Units (CTUs) need to better understand variations in the costs of their activities. Methods: Representatives of ten CTUs and two grant-awarding bodies pooled their experiences in discussions over 1.5 years. Five of the CTUs provided estimates of, and written justification for, costs associated with CTU activities required to implement an identical protocol. The protocol described a 5.5-year, nonpharmacological randomized controlled trial (RCT) conducted at 20 centres. Direct and indirect costs, the number of full time equivalents (FTEs) and the FTEs attracting overheads were compared and qualitative methods (unstructured interviews and thematic analysis) were used to interpret the results. Four members of the group (funding-body representatives or award panel members) reviewed the justification statements for transparency and information content. Separately, 163 activities common to trials were assigned to roles used by nine CTUs; the consistency of role delineation was assessed by Cohen's κ. Results: Median full economic cost of CTU activities was £769,637 (range: £661,112 to £1,383,323). Indirect costs varied considerably, accounting for between 15% and 59% (median 35%) of the full economic cost of the grant. Excluding one CTU, which used external statisticians, the total number of FTEs ranged from 2.0 to 3.0; total FTEs attracting overheads ranged from 0.3 to 2.0. Variation in directly incurred staff costs depended on whether CTUs: supported particular roles from core funding rather than grants; opted not to cost certain activities into the grant; assigned clerical or data management tasks to research or administrative staff; employed extensive on-site monitoring strategies (also the main source of variation in non-staff costs). Funders preferred written justifications of costs that described both FTEs and indicative tasks for funded roles, with itemised non-staff costs. Consistency in role delineation was fair (κ = 0.21-0.40) for statisticians/data managers and poor for other roles (κ < 0.20). Conclusions: Some variation in costs is due to factors outside the control of CTUs such as access to core funding and levels of indirect costs levied by host institutions. Research is needed on strategies to control costs appropriately, especially the implementation of risk-based monitoring strategies