Toxic inhalation of sodium metabisulphite by-products from a shipping container.

Logistics workers who handle cargo containers are at risk of toxic inhalation injuries, although prevalence and severities of these injuries are not well characterized. We report on a previously healthy 37-year-old supervisor who was acutely exposed to sodium metabisulphite and its thermal degradation by-products during a routine inspection of a shipping container. The employee developed chemical pneumonitis with acute non-cardiogenic pulmonary oedema and subsequent severe reactive airway dysfunction syndrome.

A chronic care model significantly decreases costs and healthcare utilisation in patients with inflammatory bowel disease.

INTRODUCTION: Inflammatory bowel disease (IBD) is a chronic condition, yet the model of care is often reactive. We sought to examine whether a formal IBD service (IBDS) reduced inpatient healthcare utilisation or lowered costs for inpatient care. MATERIAL AND METHODS: With protocols, routine nurse phone follow-up a help-line, more proactive care was delivered, with many symptoms and concerns dealt with prior to routine presentation. Over two five month periods before (2007/8) and after (2009/10) introducing a formal IBDS two discrete cohorts of admitted IBD patients were identified at a single centre. Each patient was assigned five contemporaneously admitted, age and gender matched controls. Inpatient healthcare utilisation was compared between patients and controls and disease-specific factors amongst the two IBD cohorts. RESULTS: The initial audit captured 102 admitted IBD patients (510 controls, median age 44 years, 57% female); the second audit 95 patients (475 controls, median age 46 years, 45.3% female). In 2009/10, the number of admissions was lower in IBD patients than in controls (mean 1.53+/-1.03 vs. 2.54+/-2.35; p<0.0001). This contrasts with the first audit, where IBD patients had more admissions than controls. Following IBDS introduction, the mean total cost of inpatient care was lower for IBD patients than controls (US$12,857.48 (US$15,236.79) vs. US$ 30,467.78 (US$ 53,760.20), p=0.005). In addition, patients known to a specialist gastroenterologist (GE) and the IBD Service tended to have the lowest mean number of admissions (GE and IBDS 1.14 (+/-0.36) vs. no GE/IBDS 1.64 (+/-1.25)). CONCLUSIONS: Healthcare utilisation and disease burden in IBD decreased significantly since introducing an IBDS. These data suggest that proactive management improved outcomes. Contact with a gastroenterologist and IBDS seemed to give best results.

Is there an association between hospital accreditation and patient satisfaction with hospital care? A survey of 37,000 patients treated by 73 hospitals.

OBJECTIVE: In many countries hospitals are undergoing accreditation as mandatory or voluntary measures. It is believed that accreditation positively influence quality of care and patient satisfaction. This survey aims at assessing the relationship between patient satisfaction and accreditation status. DESIGN: Between January and May 2007, 4 weeks after their discharge, 78 508 patients from 328 departments in 73 hospitals received a validated questionnaire. Data from 36 777 patients (response rate 55%) were available for analyses. MAIN OUTCOME MEASURES: Recommendation rate was used as primary endpoint, which was available from 35 945 patients. To address the clustering of patients within hospitals, we applied univariate and multivariable generalized estimating equations. As covariates we used 'gender' and 'age' at the patient level and the 'number of beds' and 'hospital teaching status' at the hospital level. RESULTS: Overall and not addressing the clustering, 66.3% of all the patients recommend their hospital to others. This recommendation, however, was not related to the accreditation status in the univariate analyses (odds ratio (OR) for accreditation ('yes') and recommendation ('yes') 0.99, 95% confidence interval (CI) 0.85-1.16, P= 0.92). This result was similar in the multivariable regression model adjusted for clustering (OR = 0.98, 95% CI 0.84-1.13, P= 0.74). CONCLUSIONS: Our results support the notion that accreditation is not linked to measurable better quality of care as perceived by the patient. Hospital accreditation may represent a step towards total quality management, but may not be a key factor to quality of care measured by the patient's willingness to recommend.

Antioxidant treatment with phenyl-alpha-tert-butyl nitrone (PBN) improves the cognitive performance and survival of aging rats.

Accumulating evidence has implicated free radical production and resultant oxidative damage as a major contributing factor in brain aging and cognitive decline. In the present study, aging 24-month-old rats were chronically treated with the synthetic spin-trapping antioxidant phenyl-alpha-tert-butyl nitrone (PBN) for up to 9.5 months. Chronic PBN treatment (1) improved the cognitive performance of aged rats in several tasks, (2) resulted in greater survival during the treatment period, and (3) decreased oxidative damage within brain areas important for cognitive function. These results not only provide a direct linkage between free radicals/oxidative damage and cognitive performance in old age, but also suggest that synthetic brain antioxidants could be developed to treat or prevent age-associated cognitive impairment and Alzheimer's disease.

Enhancement of ethylenethiourea recoveries in food analyses by addition of cysteine hydrochloride.

The effectiveness of cysteine hydrochloride (Cys-HCl) as a preservative of ethylenethiourea (ETU) in product matrixes and during analysis was studied. ETU recoveries were adversely affected by certain product matrixes when fortified directly into the product. Recoveries in 8 selected food items were 0-92% when analyzed 30 min after fortification and 0-51% when analyzed after 24 h. When Cys-HCl was added to product prior to fortification, recoveries increased to 71-95% even after frozen storage for 2-4 weeks. Cys-HCl was added during analysis of 53 untreated items. Recoveries improved an average of 15% with Cys-HCl. Without Cys-HCl, recoveries were erratic (20-98%), but with Cys-HCl, recoveries were 68-113%. Other antioxidants (sodium sulfite, butylated hydroxyanisole, butylated hydroxytoluene, and vitamins A and C) also were evaluated as ETU preservatives. When lettuce was treated first with sodium sulfite and then fortified with ETU, recoveries averaged 86%; without sodium sulfite, they averaged 1%. The other antioxidants were less effective for preserving ETU in lettuce, giving only 8-46% recoveries. The effect of oxidizers (potassium bromate, sodium hypochlorite, and hydrogen peroxide) on ETU recovery was also determined. Recovery of ETU from a baby food product (pears and pineapple) was 82%; with oxidizers, recoveries were 0-8%.

Determination of methylene chloride acceptability and its "purification" for ethylenethiourea methodology.

A liquid chromatographic-electrochemical method for the determination of ethylenethiourea (ETU) residues uses methylene chloride in the cleanup. Distilled-in-glass grade methylene chloride produced erratic ETU recoveries ranging from 0 to 106% for vacuum rotary evaporation of the solvent. ETU recoveries were found to be dependent on the bottle of methylene chloride used, not on supplier or lot. When GC2 grade methylene chloride from Burdick & Jackson Laboratories was used, ETU recoveries ranged from 92 to 110%. "Acceptable" ETU recoveries were defined as those values between 90 and 110%. Passing "unacceptable" methylene chloride through a column containing anhydrous sodium sulfate, sodium carbonate, and alumina was found to adequately purify methylene chloride. Treated methylene chloride provided acceptable ETU recoveries for up to 1 month after "purification."

Pharmacokinetics of the new aldosterone antagonist, spirorenone, in healthy volunteers after single and repeated daily doses.

The plasma concentrations of spirorenone in two groups of male volunteers have been determined after single and 14 daily doses of spirorenone 10 and 40 mg. Independent of the dose and pretreatment, spirorenone was absorbed with a half-life of 20-30 min, achieving maximum concentrations of about 100 ng/ml (10 mg) and 260 ng/ml (40 mg) after 1-2 h. Disposition of the parent drug was biphasic with half-lives of 50-60 min (distribution) and 5-6 h (elimination). Neither significant accumulation nor enzyme induction were observed after prolonged treatment. In one test subject given spirorenone 40 mg, the concentration of an active metabolite, 1,2-dihydrospirorenone, was measured. This compound accumulated considerably after multiple dosing and the area under the plasma concentration-time curve increased from 16 to 52% relative to that of spirorenone itself.

Management of Pseudomonas osteochondritis complicating puncture wounds of the foot.

Pseudomonas osteochondritis following puncture wounds of the foot is described in 13 children. All children had received at least one oral antibiotic and local wound therapy before admission; none had improved on these modalities. Pseudomonas aeruginosa was isolated alone from seven patients and with one or more other organisms from six patients. Initial administration of parenteral antibiotics active against Pseudomonas for one to 14 days did not result in clinical improvement. Eradication of Pseudomonas osteochondritis occurred in each patient only after thorough surgical debridement and curettage of all infected tissue. Following thorough surgical debridement, anti-Pseudomonas antibiotic therapy was continued for five to 14 days (10.8 +/- 2.7 days). The successful treatment of Pseudomonas osteochondritis should include adequate surgical debridement of all infected tissue; following thorough debridement, only one to two weeks of anti-Pseudomonas antibiotic therapy appears to be necessary.

Chloramphenicol succinate kinetics in infants and young children.

We sought to estimate the serum and urine pharmacokinetics of chloramphenicol succinate (CmS) and the effects of variation of these parameters on chloramphenicol (Cm) kinetics in 24 infants and young children ages two weeks to seven years. The mean T(1/2) of CmS was 0.40 hours; the mean body clearance was 0.72 liter/KG/hour; the mean apparent volume of distribution was 0.42 liter/kg. Variation in CmS T(1/2) did not correlate with significant variation in Cm T(1/2) (r2 = 0.002, P = 0.84). Urine collected during the dosing interval in nine patients contained 35% (mean) of the administered dose. Adjusting the infusion duration to 5 minutes or 120 minutes had no effect on the amount of CmS lost in the urine. The quantity of CmS lost in the urine affects the amount bioavailable, and secondarily the calculated volume of distribution and body clearance of Cm. We conclude that variation in urinary prodrug excretion affects the amount of Cm bioavailable to the patient, but variation in CmS T(1/2) has little effect on Cm T(1/2).

Oral chloramphenicol in the treatment of Haemophilus influenzae meningitis.

We conducted a prospective, randomized evaluation of oral chloramphenicol administration for completion of therapy of Haemophilus influenza type b meningitis in 44 children: 21 received drug by this route after the second day of therapy, the remainder continued to receive the drug intravenously. Resolution of clinical manifestations and cerebrospinal fluid indicators of meningitis was equivalent with both routes in 43 patients. One infant failed to achieve efficacious serum concentrations by either route of administration. Paired analysis of the area under the serum concentration versus time curve in 13 patients after oral and intravenous administration indicated equivalent bioavailability. Neutropenia was the only observed drug-related toxicity and correlated with the highest observed serum concentration. We conclude that: (1) chloramphenicol can be used by the oral route to complete treatment of H. influenzae type b meningitis; (2) a dose of 75 mg/kg/day is effective and less likely than higher doses to cause neutropenia; and (3) the measurement of serum chloramphenicol concentrations is important, regardless of route of administration.

Rapid estimation of chloramphenicol clearance in infants and children.

A method is presented by which chloramphenicol clearance (CL) can be estimated from a single serum sample obtained 6 hours after the initial intravenous dose. The method was evaluated prospectively in 20 infants and children who received intravenous chloramphenicol sodium succinate. Agreement between predicted and observed clearance was excellent (r = 0.914, p less than 0.001). The equation of the observed regression line was: observed 0.886x predicted + 0.019. The method appears to provide reasonably accurate estimates of clearance which can be used for rapid clinical adjustment of dose.

Chloramphenicol pharmacokinetics in infants and young children.

We measured serum chloramphenicol concentrations in 17 hospitalized pediatric patients (aged 1 month to 6 years) after intravenous infusion of chloramphenicol succinate. The serum T1/2 ranged from 2.1 to 8.3 hours with a mean of 3.98 (SD 1.75) hours, while the apparent volume of distribution ranged from 0.78 to 2.09 liters/kg with a mean of 1.39 (SD 0.34) liters/kg. The total body clearance ranged 0.122 to 0.429 liters/kg/hour with a mean of 0.281 (SD 0.117) liters/kg/hour. Two patients were restudied, and had increased clearance during their hospitalization. Because of the wide variability in pharmacokinetics, we conclude that serum chloramphenicol concentrations should be monitored in infants and children.

Hypothesis for the individualisation of drug dosage.

Computer simulations based on the pharmacokinetics of chloramphenicol and theophylline in patients, indicate a very strong correlation (r = 0.988 for chloramphenicol and r = 0.971 for theophylline) between log maintenance dose required to achieve a desired average drug concentration in serum at steady-state, and the drug concentration in serum 6 hours after an initial test dose administered by constant rate intravenous infusion over 0.5h. Accordingly, we have developed a nomogram to predict individual daily dosing requirements for these drugs in uncomplicated patients from a single serum assay following an initial dose. Within defined limits, predictions made with the nomogram are essentially equivalent to those made by iraditional pharmacokinetic methods which require substantially more drug concentration-time data following a test dose. Predictions based on the nomogram are relatively unaffected by small but typical errors in magnitude of the test dose, infusion time, sampling time and assay. Protocols for the administration of the test dose other than described, e.g. administration of an oral theophylline solution, may be equally useful for dosage predictions. In principle, this approach should apply to other drugs.

Effect of inoculum size on the susceptibility of Haemophilus influenzae b to beta-lactam antibiotics.

The current prevalence of ampicillin-resistant Haemophilus influenzae b meningitis requires accurate knowledge of susceptibility to alternative antibiotics. One variable affecting susceptibility is inoculum size. We studied the susceptibility of 200 clinical isolates of H. influenzae b to ampicillin, carbenicillin, and cefamandole at inocula of 10(5) and 10(7) CFU by two techniques. Fifty ampicillin-susceptible and fifty ampicillin-resistant strains were tested for susceptibility to ampicillin by broth dilution while 100 of each were tested by agar dilution. An inoculum effect was found, being greatest with the ampicillin-resistant strains. The range of minimal inhibitory concentrations for the resistant strains was 25 to 800 microgram of ampicillin per ml at an inoculum of 10(5) and 2,000 to less than 6,000 microgram of ampicillin at 10(7); 1.0 to 150 microgram of carbenicillin per ml at 10(5) and 6.2 to 2,000 microgram of carbenicillin per ml at 10(7); 0.4 to 2.0 microgram of cefamandole at 10(5) and 1.0 to 125 microgram/ml at 10(7). Because of this inoculum effect, we would not recommend the use of carbenicillin or cefamandole for therapy of ampicillin-resistant H. influenzae meningitis.