The DiPEP study: an observational study of the diagnostic accuracy of clinical assessment, D-dimer and chest x-ray for suspected pulmonary embolism in pregnancy and postpartum.

OBJECTIVE: To identify clinical features associated with pulmonary embolism (PE) diagnosis and determine the accuracy of decision rules and D-dimer for diagnosing suspected PE in pregnant/postpartum women DESIGN: Observational cohort study augmented with additional cases. SETTING: Emergency departments and maternity units at eleven prospectively recruiting sites and maternity units in the United Kingdom Obstetric Surveillance System (UKOSS) POPULATION: 324 pregnant/postpartum women with suspected PE and 198 pregnant/postpartum women with diagnosed PE METHODS: We recorded clinical features, elements of clinical decision rules, D-dimer measurements, imaging results, treatments and adverse outcomes up to 30 days MAIN OUTCOME MEASURES: Women were classified as having PE on the basis of imaging, treatment and adverse outcomes by assessors blind to clinical features and D-dimer. Primary analysis was limited to women with conclusive imaging to avoid work-up bias. Secondary analyses included women with clinically diagnosed or ruled out PE. RESULTS: The only clinical features associated with PE on multivariate analysis were age (odds ratio 1.06; 95% confidence interval 1.01-1.11), previous thrombosis (3.07; 1.05-8.99), family history of thrombosis (0.35; 0.14-0.90), temperature (2.22; 1.26-3.91), systolic blood pressure (0.96; 0.93-0.99), oxygen saturation (0.87; 0.78-0.97) and PE-related chest x-ray abnormality (13.4; 1.39-130.2). Clinical decision rules had areas under the receiver-operator characteristic curve ranging from 0.577 to 0.732 and no clinically useful threshold for decision-making. Sensitivities and specificities of D-dimer were 88.4% and 8.8% using a standard threshold and 69.8% and 32.8% using a pregnancy-specific threshold. CONCLUSIONS: Clinical decision rules and D-dimer should not be used to select pregnant or postpartum women with suspected PE for further investigation. Clinical features and chest x-ray appearances may have counter-intuitive associations with PE in this context. TWEETABLE ABSTRACT: Clinical decision rules and D-dimer are not helpful for diagnosing pregnant/postpartum women with suspected PE.

Non-invasive ventilation for weaning, avoiding reintubation after extubation and in the postoperative period: a meta-analysis.

Non-invasive ventilation (NIV) is a supportive therapy that improves mortality in acute respiratory failure (RF). It may also be used in patients recently extubated in intensive care units (ICUs), after operation, and to aid weaning from mechanical ventilation (MV) by reducing the morbidity and mortality associated with further MV. A meta-analysis of the available evidence was performed on the use of NIV in three areas: weaning, reduction in reintubation rates post-extubation on ICU, and reduction in RF after major surgery. Sixteen relevant randomized controlled trials were identified by three reviewers after a detailed search of identified medical databases. A meta-analysis of summary statistics relating to predetermined endpoints (ICU and hospital length of stay, ICU and hospital mortality, reintubation, pneumonia) was performed. NIV reduced the ICU length of stay when used for weaning (5.12 days) and post-surgery (0.44 days). NIV reduced reintubation rates post-surgery [odds ratio (OR) 0.24, 95% confidence interval (CI) 0.12-0.50] and the incidence of pneumonia in weaning (OR 0.12, 95% CI 0.05-0.31) and post-surgery (OR 0.27, 95% CI 0.09-0.77). There was insufficient evidence to suggest that NIV improves ICU survival, but an increased hospital survival in post-surgery (OR 4.54, [corrected] 95% CI 1.35-15.31) and a reduction after weaning (OR 0.55, 95% CI 0.31-0.98) [corrected] was seen. A meta analysis of NIV use in selected subgroups of recently extubated patients suggests that the judicious NIV use may reduce ICU and hospital length of stay, pneumonia, and reintubation rates and hospital survival.

Repeated dose study of sucralose tolerance in human subjects.

Two tolerance studies were conducted in healthy human adult volunteers. The first study was an ascending dose study conducted in eight subjects, in which sucralose was administered at doses of 1, 2. 5, 5 and 10mg/kg at 48-hour intervals and followed by daily dosing at 2mg/kg for 3 days and 5mg/kg for 4 days. In the second study, subjects consumed either sucralose (n=77) or fructose (50g/day) (n=31) twice daily in single blind fashion. Sucralose dosage levels were 125mg/day for weeks 1-3, 250mg/day during weeks 4-7, and 500mg/day during weeks 8-12. No adverse experiences or clinically detectable effects were attributable to sucralose in either study. Similarly, haematology, serum biochemistry, urinalysis and EKG tracings were unaffected by sucralose administration. In the 13-week study, serial slit lamp ophthalmologic examination performed in a random subset of the study groups revealed no changes. Fasting and 2-hour post-dosing blood sucralose concentrations obtained daily during week 12 of the study revealed no rising trend for blood sucralose. Sucralose was well tolerated by human volunteers in single doses up to 10mg/kg/day and repeated doses increasing to 5mg/kg/day for 13 weeks. Based on these studies and the extensive animal safety database, there is no indication that adverse effects on human health would occur from frequent or long-term exposure to sucralose at the maximum anticipated levels of intake.

Interlaboratory variability of rotational chair test results II: analysis of simulated data.

Standardization of rotational chair testing across laboratories has not been achieved because of differences in test protocol and analysis algorithms. The Interlaboratory Rotational Chair Study Group was formed to investigate these differences. Its first study demonstrated significant variability in calculated results using actual patient data files. No estimation of accuracy could be made, however, because the "true" values of response parameters were unknown. In this study we used simulated "patient" data files to further explore the differences among analysis algorithms. We found a high degree of agreement and accuracy across laboratories using automated analysis of high signal-to-noise/low-artifact data for gain, phase, and asymmetry. Variability increased significantly for the lower signal-to-noise ratio/higher artifact files. Operator intervention generally improved accuracy and decreased variability, but there were cases in which operator intervention reduced accuracy.

Clinicopathological evidence that neovascularisation is a cause of recurrent varicose veins.

OBJECTIVES: Recurrent varicose veins may result from poor initial surgical technique or progression of varicosities in collateral veins. In some cases new veins may develop at the saphenofemoral junction (neovascularisation) and cause recurrent saphenofemoral incompetence. This was a histological study of recurrent varicose veins. DESIGN: This clinicopathological study included 20 patients (median age 55 years) who had surgery for recurrent saphenofemoral incompetence. MATERIALS AND METHODS: A total of 28 legs had groin re-exploration with repeat flush saphenofemoral ligation. The venous tissue block from the saphenofemoral region (including the proximal thigh varicosity) was excised and orientated for histological analysis. Evidence of neovascularisation was sought using routine histological sections and S100 immunohistochemistry. RESULTS: At operation, thin-walled, serpentine neovascular veins were detected clinically as the principal cause of recurrence in 19 groins. In five groins recurrence was due to a residual missed vein at the saphenofemoral junction, and in four recurrence was caused by cross groin collaterals. On histological sections, evidence of neovascularisation was present in 27 of 28 groins. In eight it co-existed with the veins missed at the original operation but it was the sole identified cause of recurrent saphenofemoral incompetence in 19 (68%) groins. CONCLUSIONS: Neovascularisation was the principal cause of recurrent saphenofemoral incompetence in this series.

Interlaboratory variability of rotational chair test results. Interlaboratory Rotational Chair Study Group.

Test-retest reliability of rotational chair testing for a single facility has previously been examined by others. The actual data analysis methods, however, have received far less attention. The variety of both hardware and software currently used theoretically may affect the results for a given subject tested at different facilities. The purposes of this study were, first, to quantify the amount of variability in the analysis of identical raw data files at multiple rotational chair testing facilities by using automated analysis; second, to evaluate the effect of operator intervention on the analysis; and third, to identify possible sources of variability. Raw data were collected from 10 normal subjects at 0.05 Hz and 0.5 Hz (50 degrees per second peak velocity). Diskettes containing raw electro-oculogram data files were then distributed to eight participating laboratories for analysis by two methods: (1) using automated analysis algorithms and (2) using the same algorithms but allowing operator intervention into the analysis. Response parameters calculated were gain and phase (re: velocity). The SD of gain values per subject for automated analysis ranged from 0.01 to 0.32 gain units and of phase values from 0.4 to 13.7 degrees. For analysis with operator intervention, the SD of gain values ranged from 0.02 to 0.10 gain units and of phase values from 0.4 to 4.4 degrees. The difference between automated analysis and analysis with operator intervention was significant for gain calculations (p < 0.02) but not for phase calculations (p > 0.05). This study demonstrates significant variability in automated analysis of rotational chair raw data for gain and phase.(ABSTRACT TRUNCATED AT 250 WORDS)

Triglyceride lowering effect of MaxEPA fish lipid concentrate: a multicentre placebo controlled double blind study.

A multicentre, double blind, randomised between-group study comparing the triglyceride lowering effect of MaxEPA, a natural marine oil, and a placebo control is described. Eighty-six patients with hypertriglyceridaemia (fasting serum triglyceride greater than or equal to 2 mmol/l) were studied for three months. There were no significant differences between the groups (48 active, 38 control) in respect of age, sex, height or weight, smoking habits or alcohol consumption. After one month triglyceride levels were reduced significantly from baseline in the treatment group and there was also a highly significant difference between the groups in favour of the marine oil. There was no significant change in serum total cholesterol in either group but there were fluctuations in high density lipoprotein (HDL) in both groups. Minor gastrointestinal side effects were reported by patients in both groups. Standard haematological and biochemical tests were done and there were no significant changes from baseline.

Bioavailability of potassium from controlled-release tablets with and without water loading.

The relative availability of potassium from a controlled-release multiple-units tablet (Kalinorm) and a single-unit tablet (Slow-K) were compared in 13 volunteers on a low potassium diet (less than 30 mmol), by observing changes in urinary potassium excretion after administration of a single dose of 32 mmol potassium, either with or without water loading. Irrespective of procedure, the two products had the same extent of availability. The use of water loading, and special precautions about the level of dietary potassium and its composition when studying urinary potassium excretion, are discussed. It is suggested that water loading should be avoided when investigating the rate of potassium excretion.