Impact of recent intravenous chemotherapy on outcome in severe sepsis and septic shock patients with hematological malignancies

Objective To compare the characteristics and outcome of patients with hematological malignancies referred to the ICU with severe sepsis and septic shock who had or had not received recent intravenous chemotherapy, defined as within 3 weeks prior to ICU admission. Design and setting Retrospective observational cohort study on prospectively collected data in a medical ICU of a university hospital. Patients 186 ICU patients with hematological malignancies with severe sepsis or septic shock (2000–2006). Measurements and results There were 77 patients admitted with severe sepsis and 109 with septic shock; 91 (49%) had received recent intravenous chemotherapy. Patients with recent chemotherapy more often had a high-grade malignancy and were more often neutropenic, less often had pulmonary infiltrates, and less often required mechanical ventilation. ICU, 28-day, in-hospital, and 6-month mortality rates were 33% vs. 48.4%, 40.7% vs. 57.4%, 45.1% vs. 58.9%, and 50.5% vs. 63.2% in patients with and without recent chemotherapy, respectively. Logistic regression identified four variables independently associated with 28-day mortality: SOFA score at ICU admission, pulmonary site of infection, and fungal infection were associated with worse outcome whereas previous intravenous chemotherapy was protective at borderline significance. After adjustment with a propensity score for recent chemotherapy, chemotherapy was not associated with outcome. Conclusions Patients referred to the ICU with severe sepsis and septic shock complicating active chemotherapeutic treatment have better prognosis than commonly perceived. This article is discussed in the editorial available at: .     

A quantitative appraisal of interference by icodextrin metabolites in point-of-care glucose analyses.

An important number of patients dependent on renal dialysis prefer peritoneal dialysis to hemodialysis. In the case of peritoneal dialysis, the glucose polymer icodextrin is frequently added to the dialysis fluid as an osmotic agent, since this polymer is able to maintain an osmotic gradient across the peritoneal membrane longer than monomeric glucose, leading to a prolonged effective ultrafiltration time. It was previously shown that icodextrin is partly able to enter the blood via the lymphatic system, where hydrolysis to glucose oligomers such as maltose and maltotriose occurs. The presence of these oligomers in the blood appears to cause significant overestimations of the glucose values in several point-of-care (POC) glucose analyzers, with potentially dramatic consequences. This effect has been investigated for a series of POC glucose analyzers, both by analyzing the blood of peritoneal dialysis patients and by an in vitro investigation of the quantitative effects of maltose and maltotriose. In particular, POC analyzers utilizing the bacterially produced enzyme glucose dehydrogenase seem to lack glucose specificity.     

Characterization of human skin equivalents developed at body's core and surface temperatures

Human skin equivalents (HSEs) are in vitro developed three‐dimensional models resembling native human skin (NHS) to a high extent. However, the epidermal lipid biosynthesis, barrier lipid composition, and organization are altered, leading to an elevated diffusion rate of therapeutic molecules. The altered lipid barrier formation in HSEs may be induced by standardized culture conditions, including a culture temperature of 37°C, which is dissimilar to skin surface temperature. Therefore, we aim to determine the influence of culture temperature during the generation of full thickness models (FTMs) on epidermal morphogenesis and lipid barrier formation. For this purpose, FTMs were developed at conventional core temperature (37°C) or lower temperatures (35°C and 33°C) and evaluated over a time period of 4 weeks. The stratum corneum (SC) lipid composition was analysed using advanced liquid chromatography coupled to mass spectrometry analysis. Our results show that SC layers accumulated at a similar rate irrespective of culture temperature. At reduced culture temperature, an increased epidermal thickness, a disorganization of the lower epidermal cell layers, a delayed early differentiation, and an enlargement of granular cells were detected. Interestingly, melanogenesis was reduced at lower temperature. The ceramide subclass profile, chain length distribution, and level of unsaturated ceramides were similar in FTMs generated at 37°C and 35°C but changed when generated at 33°C, reducing the resemblance to NHS. Herein, we report that culture temperature affects epidermal morphogenesis substantially and to a lesser extent the lipid barrier formation, highlighting the importance of optimized external parameters during reconstruction of skin.     

Proposed outcome measures for prospective clinical trials in juvenile idiopathic arthritis–associated uveitis: A consensus effort from the multinational interdisciplinary working group for uveitis in childhood

Objective

To develop a set of core outcome measures for use in randomized controlled trials (RCTs) and longitudinal observational studies in juvenile idiopathic arthritis (JIA)–associated uveitis.

Methods

The literature relating to outcome measures used in studies of uveitis in childhood and adolescence was reviewed. A set of core outcomes and domains was established using the Delphi process. This was reviewed by a representative multinational interdisciplinary working group. Nominal group technique consensus was reached on face and content validity of the range and content of the domains. The outcomes and the appropriate instruments for uveitis trials were adapted to the age ranges of patients with JIA‐associated uveitis.

Results

Consensus was reached that data should be reported at defined time points in longitudinal studies with patients stratified by prognostic markers. Visual acuity testing should be age appropriate. The severity of uveitis (measured as anterior chamber cell grade) and duration of active inflammation should be documented. Visually significant structural complications should be recorded and quantified with standard measures. The responses to treatment and corticosteroid‐sparing effects of treatment should be documented. Patient‐reported disease activity and age‐specific uveitis‐related quality of life should be reported using appropriate questionnaires.

Conclusion

The proposed outcome measures in JIA‐associated uveitis should aid in the standardization and comparison of future RCTs of the treatment regimens for this disease. The proposed outcome measures will be verified in a prospective validation study.     

Carotid stiffness and the risk of new vascular events in patients with manifest cardiovascular disease. The SMART study.

AIMS: To study whether arterial stiffness is related to risk of new vascular events in patients with manifest arterial disease and to examine whether this relation varies between patients who differ with respect to baseline vascular risk, arterial stiffness, or systolic blood pressure (SBP). METHODS AND RESULTS: The study was performed in the first consecutive 2183 patients with manifest arterial disease enrolled in the SMART study (Second Manifestations of ARTerial disease), a cohort study among patients with manifest arterial disease or cardiovascular risk factors. Common carotid distension (i.e. the change in carotid diameter in systole relative to diastole) was measured at baseline by ultrasonography. With the distension, several stiffness parameters were determined. In the entire cohort, none of the carotid artery stiffness parameters was related to the occurrence of vascular events. However, decreased stiffness was related to decreased vascular risk in subjects with low baseline SBP. The relation of carotid stiffness with vascular events did not differ between tertiles of baseline risk and carotid stiffness. CONCLUSION: Carotid artery stiffness is no independent risk factor for vascular events in patients with manifest arterial disease. However, in patients with low SBP, decreased carotid stiffness may indicate a decreased risk of vascular events.     

Exploring the Development of Existing Sex Education Programmes for People with Intellectual Disabilities: An Intervention Mapping Approach

Background

People with intellectual disabilities face barriers that affect their sexual health. Sex education programmes have been developed by professionals working in the field of intellectual disabilities with the aim to overcome these barriers. The aim of this study was to explore the development of these programmes.

Methods

Sex education programmes geared to people with intellectual disabilities were examined in the context of the Intervention Mapping protocol. Data were obtained via interviews with the programme developers.

Results

All programmes lack specific programme outcomes, do not have a theoretical basis, did not involve members of relevant groups in the development process and lack systematic evaluation.

Conclusions

Based on our findings and the literature, we conclude that these programmes are unlikely to be effective. Future programmes should be developed using a more systematic and theory‐ and evidence‐based approach.     

Evaluation of a preparation depth controlling device: a pilot study.

OBJECTIVE: To define the reproducibility and accuracy of the Prepometer device (Hager & Werken) and to correlate the measured electrical resistance with the remaining dentin thickness. METHOD AND MATERIALS: In vivo standardized cavities were made on the buccal side in the cervical region of 12 intact teeth. Measurements with the Prepometer were completed before tooth extraction. After extraction, in vitro measurements of the remaining dentin thickness were performed using a microfocus-computerized tomography scanner. These in vitro scan data were compared with the in vivo measurements, and correlation coefficients calculated. The intra- and interinvestigator variability were defined, using a paired 2-tailed Student t test. The level of significance was set at 5%. RESULTS: Although both the intra- and interinvestigator variability scored well, there was no clear correlation between the Prepometer measurements and the remaining dentin thickness. Because the device determines the electrical resistance of the dentin, which is related to dentin permeability, real remaining dentin thickness cannot be measured. A reasonable safety zone (3 of 12 teeth scored false negative and 1 of 12 teeth scored false positive) in terms of remaining dentin thickness was observed. CONCLUSIONS: The Prepometer, a device developed to screen dentin-surface permeability by measuring its electrical resistance, was shown to be reproducible in its use. However, electrical resistance was shown not to correlate with dentin thickness. Although the Prepometer might help to estimate the risk of pulp injury after tooth preparation, its effectiveness still remains to be proven in a randomized clinical trial.     

A Cross-Section Device To Improve Visualization of Fluorescent Probe Penetration into the Skin by Confocal Laser Scanning Microscopy

Pharmaceutical Research -