Test methods for estimating the efficacy of the fast-acting disinfectant peracetic acid on surfaces of personal protective equipment.

AIMS: The work aimed at developing and evaluating practically relevant methods for testing of disinfectants on contaminated personal protective equipment (PPE). METHODS AND RESULTS: Carriers were prepared from PPE fabrics and contaminated with Bacillus subtilis spores. Peracetic acid (PAA) was applied as a suitable disinfectant. In method 1, the contaminated carrier was submerged in PAA solution; in method 2, the contaminated area was covered with PAA; and in method 3, PAA, preferentially combined with a surfactant, was dispersed as a thin layer. In each method, 0·5-1% PAA reduced the viability of spores by a factor of ≥6 log10 within 3 min. The technique of the most realistic method 3 proved to be effective at low temperatures and also with a high organic load. Vaccinia virus and Adenovirus were inactivated with 0·05-0·1% PAA by up to ≥6 log10 within 1 min. The cytotoxicity of ricin was considerably reduced by 2% PAA within 15 min of exposure. CONCLUSIONS: PAA/detergent mixture enabled to cover hydrophobic PPE surfaces with a thin and yet effective disinfectant layer. SIGNIFICANCE AND IMPACT OF THE STUDY: The test methods are objective tools for estimating the biocidal efficacy of disinfectants on hydrophobic flexible surfaces.

Ferric maltol therapy for iron deficiency anaemia in patients with inflammatory bowel disease: long-term extension data from a Phase 3 study.

BACKGROUND: Ferric maltol was effective and well-tolerated in iron deficiency anaemia patients with inflammatory bowel disease during a 12-week placebo-controlled trial. AIM: To perform a Phase 3 extension study evaluating long-term efficacy and safety with ferric maltol in inflammatory bowel disease patients in whom oral ferrous therapies had failed to correct iron deficiency anaemia. METHODS: After 12 weeks of randomised, double-blind treatment, patients with iron deficiency anaemia and mild-to-moderate ulcerative colitis or Crohn's disease received open-label ferric maltol 30 mg b.d. for 52 weeks. RESULTS: 111 patients completed randomised treatment and 97 entered the open-label ferric maltol extension. In patients randomised to ferric maltol ('continued'; n = 50), mean ± s.d. haemoglobin increased by 3.07 ± 1.46 g/dL between baseline and Week 64. In patients randomised to placebo ('switch'; n = 47), haemoglobin increased by 2.19 ± 1.61 g/dL. Normal haemoglobin was achieved in high proportions of both continued and switch patients (89% and 83% at Week 64, respectively). Serum ferritin increased from 8.9 µg/L (baseline) to 26.0 µg/L (Week 12) in ferric maltol-treated patients, and to 57.4 µg/L amongst all patients at Week 64. In total, 80% of patients reported ≥1 adverse event by Week 64. Adverse events considered related to ferric maltol were recorded in 27/111 (24%) patients: 8/18 discontinuations due to adverse events were treatment-related. One patient was withdrawn due to increased ulcerative colitis activity. CONCLUSIONS: Normal haemoglobin was observed in ≥80% of patients from weeks 20-64 of long-term ferric maltol treatment, with concomitant increases in iron storage parameters. Ferric maltol was well-tolerated throughout this 64-week study.

Hypersensitivity to intravenous iron: classification, terminology, mechanisms and management.

Intravenous (IV) iron therapy is widely used in iron deficiency anaemias when oral iron is not tolerated or ineffective. Administration of IV-iron is considered a safe procedure, but severe hypersensitivity reactions (HSRs) can occur at a very low frequency. Recently, new guidelines have been published by the European Medicines Agency with the intention of making IV-iron therapy safer; however, the current protocols are still non-specific, non-evidence-based empirical measures which neglect the fact that the majority of IV-iron reactions are not IgE-mediated anaphylactic reactions. The field would benefit from new specific and effective methods for the prevention and treatment of these HSRs, and the main goal of this review was to highlight a possible new approach based on the assumption that IV-iron reactions represent complement activation-related pseudo-allergy (CARPA), at least in part. The review compares the features of IV-iron reactions to those of immune and non-immune HSRs caused by a variety of other infused drugs and thus make indirect inferences on IV-iron reactions. The process of comparison highlights many unresolved issues in allergy research, such as the unsettled terminology, multiple redundant classifications and a lack of validated animal models and lege artis clinical studies. Facts and arguments are listed in support of the involvement of CARPA in IV-iron reactions, and the review addresses the mechanism of low reactogenic administration protocols (LRPs) based on slow infusion. It is suggested that consideration of CARPA and the use of LRPs might lead to useful new additions to the management of high-risk IV-iron patients.

Decontamination of a BSL3 laboratory by hydrogen peroxide fumigation using three different surrogates for Bacillus anthracis spores.

AIMS: Two independent trials investigated the decontamination of a BSL3 laboratory using vaporous hydrogen peroxide and compared the effect on spores of Bacillus cereus, Bacillus subtilis and Bacillus thuringiensis as surrogates for Bacillus anthracis spores, while spores of Geobacillus stearothermophilus served as control. METHODS AND RESULTS: Carriers containing 1·0 × 10(6) spores were placed at various locations within the laboratory before fumigation with hydrogen peroxide following a previously validated protocol. Afterwards, carriers were monitored by plating out samples on agar and observing enrichment in nutrient medium for up to 14 days. Three months later, the experiment was repeated and results were compared. On 98 of 102 carriers, no viable spores could be detected after decontamination, while the remaining four carriers exhibited growth of CFU only after enrichment for several days. Reduction factors between 4·0 and 6·0 log levels could be reached. CONCLUSIONS: A validated decontamination of a laboratory with hydrogen peroxide represents an effective alternative to fumigation with formaldehyde. Spores of B. cereus seem to be more resistant than those of G. stearothermophilus. SIGNIFICANCE AND IMPACT OF THE STUDY: The results of this study provide important results in the field of hydrogen peroxide decontamination when analysing the effect on spores other than those of G. stearothermophilus.

Efficacy, safety and tolerability of vidofludimus in patients with inflammatory bowel disease: the ENTRANCE study.

BACKGROUND: Vidofludimus (SC12267) is a novel oral immunomodulator inhibiting dihydroorotate dehydrogenase (DHODH) and the expression of proinflammatory cytokines including interleukin-17 (IL17A and IL17F) and interferon-gamma. The objective of the study was to explore the efficacy, safety and tolerability of vidofludimus in steroid-dependent inflammatory bowel disease (IBD). METHODS: The open label uncontrolled ENTRANCE study (ClinicalTrials.gov NCT00820365) has been conducted at 13 study centers in Germany, Bulgaria and Romania. Thirty-four steroid-dependent patients with a confirmed diagnosis of Crohn's disease (CD) or ulcerative colitis (UC) were treated with a once daily 35mg oral dose of vidofludimus over 12weeks. Steroids were tapered during the first 8weeks followed by a steroid-free treatment period of 4weeks. Complete response was defined as steroid-free clinical remission at week 12; partial response was defined as being in remission at steroid dose equal or lower than the individual patient's threshold dose for relapse. RESULTS: Of the thirty-four patients enrolled in this trial 26 were evaluable for primary efficacy assessment. After completion of the 12weeks treatment phase 8 out of 14 (57.1%) patients with CD and 6 out of 12 (50.0%) patients with UC were in steroid-free remission (complete responders). Another 4 (28.6%) patients in CD and 5 (41.7%) patients in UC were partial responders. Vidofludimus was well tolerated, no drug-related serious adverse events were observed. CONCLUSIONS: This trial provides first evidence of clinical efficacy of vidofludimus in IBD. Although the safety and tolerability profile seems favorable, long-term controlled studies are needed to further investigate its potential as novel IBD therapy.

Low dose balsalazide (1.5 g twice daily) and mesalazine (0.5 g three times daily) maintained remission of ulcerative colitis but high dose balsalazide (3.0 g twice daily) was superior in preventing relapses.

BACKGROUND: Balsalazide is a new 5-aminosalicylic acid (5-ASA) containing prodrug. Its efficacy in comparison with standard mesalazine therapy and the optimum dose for maintaining remission of ulcerative colitis are still unclear. AIMS: To compare the relapse preventing effect and safety profile of two doses of balsalazide and a standard dose of Eudragit coated mesalazine. METHODS: A total of 133 patients with ulcerative colitis in remission were recruited to participate in a double blind, multicentre, randomised trial: 49 patients received balsalazide 1.5 g twice daily, 40 received balsalazide 3.0 g twice daily, and 44 received mesalazine 0.5 g three times daily. Efficacy assessments were clinical activity index (CAI) and endoscopic score according to Rachmilewitz, and a histological score. In addition, laboratory tests were performed and urinary excretion of 5-ASA and its metabolite N-Ac-5-ASA was analysed. The study lasted for 26 weeks. RESULTS: Balsalazide 3.0 g twice daily resulted in a significantly higher clinical remission rate (77.5%) than balsalazide 1.5 g twice daily (43.8%) and mesalazine 0.5 g three times daily (56.8%) (p=0.006). The respective times to relapse were 161 days, 131 days (p=0.003), and 144 days (NS). Accordingly, pairwise contrasts of the final endoscopic score demonstrated a significant difference (p=0.005) between the two balsalazide treatment groups while differences between either of these two groups and mesalazine were not statistically significant. Patients treated with balsalazide excreted less 5-ASA and N-Ac-5-ASA than patients receiving mesalazine but these differences were not statistically significant. Discontinuation of the trial because of adverse effects occurred in nine patients: three in the balsalazide 1.5 g twice daily group, two in the balsalazide 3.0 g twice daily group, and four in the mesalazine 0.5 g three times daily group. No clinically important new drug safety related findings were identified in this study. CONCLUSIONS: High dose balsalazide (3.0 g twice daily) was superior in maintaining remission in patients with ulcerative colitis compared with a low dose (1.5 g twice daily) or a standard dose of mesalazine (0.5 g three times daily). All three treatments were safe and well tolerated.

Cost-effectiveness of ceftriaxone 1 g vs second-generation cephalosporins in the treatment of pneumonia in general medical wards in Germany.

The cost-effectiveness of ceftriaxone 1 g in the treatment of pneumonia in general medical wards was compared with that of second-generation cephalosporins. A total of 1,706 patients were treated with either a second-generation cephalosporin (cefotiam, cefuroxime) or ceftriaxone (single daily dose of 1 g), and 604 in each group were included in a matched-pair analysis. Cure or improvement in response to monotherapy was observed in 81.4% of patients on cefuroxime/cefotiam vs 91% of those on ceftriaxone (P < 0.0001). Adverse events occurred with equal frequency in both groups (1.9%). In terms of mean hospital costs for antimicrobial medication, the staff required to administer it as well as laboratory and X-ray examinations, effective treatment with ceftriaxone is DM 193/$ 105 (25%) less expensive than effective treatment with a second-generation cephalosporin (P < 0.001). From the perspective of the health insurance, the costs for a patient treated with ceftriaxone are DM 3,910/$ 2,140 vs DM 4,392/$ 2,400 for a patient treated with a second-generation cephalosporin (March 1998: USD 1 = DM 1.83).

Renal tubular dysfunction in patients with inflammatory bowel disease treated with aminosalicylate.

BACKGROUND: An increasing number of case reports indicate potential nephrotoxicity of 5-aminosalicylic acid (5-ASA), which shares similarities with the chemical structures of both phenacetin and acetylsalicylic acid. AIM: In a point prevalence study the occurrence of sensitive indices indicative of early kidney malfunction was assessed in outpatients with inflammatory bowel disease. METHODS: Routine indices of kidney function (creatinine clearance, urinary protein content, pH, electrolytes, and microscopy) were investigated in 223 patients with inflammatory bowel disease as well as sensitive markers of glomerular or tubular dysfunction (microproteinuria by SDS polyacrylamide gel electrophoresis (SDS-PAGE), urinary concentrations of N-acetyl-beta-D-glucosaminidase, alpha 1-microglobulin, gamma-glutamyltransferase (GGT), alkaline phosphatase (AP), and albumin). Histories of exposure to 5-ASA were assessed by questionnaire. RESULTS: Patients receiving high amounts of 5-ASA, both actual as well as on a lifetime basis, showed an increased prevalence of tubular proteinuria by SDS-PAGE. Raised values for urinary AP and GGT indicate proximal tubular epithelial cells as the source. All other kidney function tests were normal. Analysis of covariates indicated strong associations between disease activity and size of 5-ASA doses as well as alterations in kidney tubular function. CONCLUSION: The possibility exists that high doses of 5-ASA may be associated with proximal tubular proteinuria. This point prevalence study cannot dissect the possible impact of chronic inflammation from high dose 5-ASA treatment and further prospective studies are warranted.

Recombinant erythropoietin for the treatment of anemia in inflammatory bowel disease.

BACKGROUND: Some patients with inflammatory bowel disease have anemia that is refractory to treatment with iron and vitamins. We examined whether administering iron and recombinant erythropoietin could raise hemoglobin levels in such patients. METHODS: Thirty-four patients with inflammatory bowel disease (15 with ulcerative colitis and 19 with Crohn's disease) and anemia refractory to iron therapy (hemoglobin concentrations below 10.0 g per deciliter [6.2 mmol per liter]) were randomly assigned in a prospective, double-blind, 12-week trial to receive either oral iron (100 mg per day) and subcutaneous erythropoietin (150 U per kilogram of body weight twice per week) (n=17) or oral iron and placebo (n=17). The primary measure of efficacy was an increase in hemoglobin levels of more than 1.0 g per deciliter (0.62 mmol per liter). Additional analyses were performed with other patients with inflammatory bowel disease. RESULTS: The severity of anemia was related to clinical disease activity as well as to in vitro monocyte secretion of interleukin-1 beta, a proinflammatory cytokine. Serum erythropoietin concentrations were increased in 52 randomly selected outpatients with inflammatory bowel disease and anemia, but the concentrations were inadequate in relation to the degree of anemia. Twelve weeks of therapy with recombinant erythropoietin and oral iron increased mean (+/-SE) hemoglobin concentrations from 8.81+/-0.27 g per deciliter (5.47+/-0.17 micromol per liter) to 10.52+/-0.41 g per deciliter (6.5+/-0.25 micromol per liter), whereas hemoglobin concentrations in the placebo group decreased from 8.69+/-0.11 g per deciliter (5.4+/-0.068 micromol per liter) to 7.84+/- 0.33 g per deciliter (4.9+/-0.2 mmol per liter) (P<0.001). After 12 weeks, hemoglobin levels had increased by more than 1.0 g per deciliter in 82 percent of the patients in the erythropoietin group, as compared with 24 percent of those in the placebo group (P=0.002). There were five treatment failures in the placebo group and two in the erythropoietin group (P=0.18); treatment failure was defined as a decrease in hemoglobin levels of more than 2.0 g per deciliter (1.24 micromol per liter) to a value below 8.0 g per deciliter (4.96 micromol per liter) or any decrease to less than 6.5 g per deciliter (4.03 micromol per liter). CONCLUSIONS: In patients with inflammatory bowel disease and anemia refractory to treatment with iron and vitamins, treatment with oral iron and recombinant erythropoietin can raise hemoglobin levels.

Oral 4-aminosalicylic acid versus 5-aminosalicylic acid slow release tablets. Double blind, controlled pilot study in the maintenance treatment of Crohn's ileocolitis.

4-Aminosalicylic acid (4-ASA) has been suggested as an effective treatment for both active and quiescent ulcerative colitis. 5-Aminosalicylic acid (5-ASA) is well accepted for the maintenance treatment of inactive ulcerative colitis. Moreover, recent studies suggest that 5-ASA may also be effective in maintaining remission in Crohn's colitis. As treatment with 4-ASA may result in less side effects, the efficacy of a one year's maintenance treatment with oral 4-ASA (1.5 g/d, slow release tablets, n = 19) and oral 5-ASA (1.5 g/d, slow release tablets, n = 21) was compared in a double blind, randomised trial in patients with quiescent Crohn's ileocolitis. Patients with ileocolonic or colonic involvement were enrolled if in stable remission for more than two months but less than one year. Baseline demography and clinical severity were similar in both groups. Total colonoscopy and ileoscopy were performed at enrollment and at the end of the study. After one year seven of 19 patients receiving 4-ASA (36%) and 8 of 21 receiving 5-ASA (38%) had developed a clinical relapse, as defined by a rise in the Crohn's disease activity index (CDAI) of more than 100 points to values higher than 150. The relapse rates between the 4-ASA and the 5-ASA groups were not statistically different although no comparison with the spontaneous relapse rate in a placebo group could be made. Clinical relapse was accompanied by a statistically significant rise in serum concentrations of soluble interleukin 2 receptor and by an increased percentage of activated peripheral blood T cells. There were no statistical differences between the 4-ASA and the 5-ASA groups regarding the height of rise in CDAI or of soluble interleukin 2 receptor concentrations during relapse, thus showing a similar severity relapsed disease activity. In conclusion, 4-ASA maybe as effective as 5-ASA in the maintenance treatment of quiescent Crohn's disease and there were no differences in the severity of relapse between both treatment groups.