Fulminant Clostridium difficile: an underappreciated and increasing cause of death and complications

OBJECTIVE: To review the epidemiology and characteristics of patients who died or underwent colectomy secondary to fulminant Clostridium difficile colitis. SUMMARY BACKGROUND DATA: In patients with C. difficile colitis, a progressive, systemic inflammatory state may develop that is unresponsive to medical therapy; it may progress to colectomy or death. METHODS: The authors reviewed 2,334 hospitalized patients with C. difficile colitis from January 1989 to December 2000. Sixty-four patients died or underwent colectomy for pathologically proven C. difficile colitis. RESULTS: In 2000, the incidence of C. difficile colitis in hospitalized patients increased from a baseline of 0.68% to 1.2%, and the incidence of patients with C. difficile colitis in whom life-threatening symptoms developed increased from 1.6% to 3.2%. Forty-four patients required a colectomy and 20 others died directly from C. difficile colitis. Twenty-two percent had a prior history of C. difficile colitis. A recent surgical procedure and immunosuppression were common predisposing conditions. Lung transplant patients were 46 times more likely to have C. difficile colitis and eight times more likely to have severe disease. Abdominal computed tomography scan correctly diagnosed all patients, whereas 12.5% of toxin assays and 10% of endoscopies were falsely negative. Patients undergoing colectomy for C. difficile colitis had an overall death rate of 57%. Significant predictors of death after colectomy were preoperative vasopressor requirements and age. CONCLUSIONS: C. difficile colitis is a significant and increasing cause of death. Surgical treatment of C. difficile colitis has a high death rate once the fulminant expression of the disease is present.     

Epogam evening primrose oil treatment in atopic dermatitis and asthma

Essential fatty acids are claimed to have positive effects in atopic diseases. In a double blind, placebo controlled, parallel group study 58 out of 60 children, with atopic dermatitis and the need for regular treatment with topical skin steroids, completed a 16 weeks' treatment period with either Epogam evening primrose oil or placebo capsules. Twenty two of these subjects also had asthma. The parents used diaries to record symptom scores and concomitant medication. Peak expiratory flow was measured and disease activity was monitored by the clinician every four weeks. The plasma concentrations of essential fatty acids increased significantly in the group treated with Epogam capsules. The study demonstrated significant improvements of the eczema symptoms but no significant difference was found between the placebo and the Epogam groups. No therapeutic effect was shown on asthma symptoms or fidget.     

Pericardial effusion complicating a percutaneous central venous line in a neonate

A premature infant developed pericardial effusion four days after the insertion of a 25-gauge silastic percutaneous central venous catheter. The effusion contained parenteral nutrition fluid and resolved rapidly after withdrawal of the catheter. Pericardial effusion is a potential complication of percutaneous, as well as surgically placed, central venous catheters.     

The STR system in the human phenylalanine hydroxylase gene: true fragment length obtained with fluorescent labelled PCR primers

We present a simple, fast, non-radioactive method for the analysis of the polymorphic short tandem repeat (STR) system in the human phenylalanine hydroxylase gene. Previously, sizing of the STR marker involved radiolabelling of PCR amplified fragments and resolution on denaturing polyacrylamide gels using M13 sequencing ladder as a standard. However, this method consistently gave sizes 2 bp longer than the known sequence. The fluorescent method presented here employs internal lane standards and enables accurate sizing of the fragments. To avoid confusion, we suggest that the true fragment lengths are used as reference values in the future. The analysis of STR alleles is valuable for population genetic studies and for targeted mutation screening in phenylketonuria (PKU). It can replace RFLP-based haplotype analysis for carrier detection, and we report its use for prenatal diagnosis in a Northern Irish family with PKU. The analysis of 250 Northern Irish chromosomes, including 128 PKU alleles, showed no significant difference between normal and PKU alleles, with fragment lengths of 238 and 242 bp most common in both groups.     

Molecular analysis of PKU in Ireland

Classical phenylketonuria (PKU: McKusick No. 261600) is caused by mutations occurring at the phenylalanine hydroxylase (PAH) locus on chromosome 12 and has a prevalence in Ireland of 1 in 4500. We examined 304 independent alleles from 350 patients for the presence of six mutations and have characterized VNTR alleles within the minisatellite region 3' to the PAH gene in patients carrying the most prevalent mutation. R408W was the most common mutation found, with a relative frequency of 42%. All other mutations had relative frequencies of <10%. VNTR analysis showed that the R408W mutation is associated with the VNTR-8 allele in the Irish population, indicating that R408W is associated with RFLP haplotype 1. This differs from that reported from eastern Europe where R408W is associated with RFLP haplotype 2/VNTR-3; an observation which has led several groups to propose a Balto-Slavic origin for this mutation. These results support the hypothesis of a second, independent founding event for the R408W mutation on an RFLP haplotype 1 VNTR-8 chromsome background in the Irish/Celtic population.     

Fructosamine and glycated haemoglobin in the assessment of long term glycaemic control in diabetes

Fructosamine and glycated haemoglobin were measured simultaneously in 147 children with diabetes. If glycated haemoglobin is considered as the 'gold standard' for long term glycaemic control, then fructosamine is a poor indicator of actual glycated haemoglobin values, with wide 95% confidence (fiducial) limits. This shows that it is impossible to accurately predict glycated haemoglobin concentrations and therefore, by implication, longer term glycaemic control, from measurements of fructosamine. As the major studies on the prevention of microvascular complications in diabetes have used glycated haemoglobin levels to assess glycaemic control, it is suggested that this measurement should be used in all children with diabetes in preference to the measurement of fructosamine.     

Identifying potentially ineffective care in a community hospital

OBJECTIVES: To develop a formula to predict mortality for intensive care unit patients between day 5 in an intensive care unit and 100 days after hospital discharge from a community hospital. DESIGN: Retrospective 1-yr derivation study with validation on a subsequent year's intensive care unit population. SETTING: An 850-bed, not-for-profit community hospital with three adult intensive care units, including medical-surgical, cardiac-medical, and cardiac-surgical units. PATIENTS: The development patient set included 4045 consecutive adult admissions to the intensive care unit between July 1995 and June 1996. The validation sample consisted of 4084 admissions between July 1996 and June 1997. RESULTS: During the first year, 100-day posthospital discharge mortality was predicted by the combination Acute Physiology and Chronic Health Evaluation (APACHE) III predicted mortality on day 5 of >0.92 or the product of day 1 and day 5 APACHE predicted mortality of >0.40, with an increase in the APACHE predicted mortality from day 1 to day 5 of >0.10. Specificity in the development cohort was 0.99, sensitivity was 0.30, and positive predictive value was 0.95. The second-year validation study demonstrated a specificity, sensitivity, and positive predictive value of 0.98, 0.29, and 0.91, respectively, when applying the model to the validation sample. CONCLUSIONS: By using readily available APACHE III data, we were able to identify patients at high risk of dying between intensive care unit day 5 and 100 days after discharge. Although the low sensitivity limits the number of patients for whom death at 100 days is predicted, the high specificity and positive predictive value suggests this information may provide useful information for families and physicians. If these formulas can be validated in diverse institutional settings, decisions regarding short- and long-term outcomes may be improved by using objective survival predictions from two time points.