Treatment of Hidradenitis Suppurativa Evaluation Study (THESEUS): a prospective cohort study.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic, painful disease affecting flexures and other skin regions, producing nodules, abscesses and skin tunnels. Laser treatment targeting hair follicles and deroofing of skin tunnels are standard HS interventions in some countries but are rarely offered in the UK. OBJECTIVES: To describe current UK HS management pathways and influencing factors to inform the design of future randomized controlled trials (RCTs). METHODS: THESEUS was a nonrandomized 12-month prospective cohort study set in 10 UK hospitals offering five interventions: oral doxycycline 200 mg daily; oral clindamycin and rifampicin both 300 mg twice daily for 10 weeks, extended for longer in some cases; laser treatment targeting hair follicles; deroofing; and conventional surgery. The primary outcome was the combination of clinician-assessed eligibility and participant hypothetical willingness to receive each intervention. The secondary outcomes were the proportion of participants selecting each intervention as their final treatment option; the proportion who switch treatments; treatment fidelity; and attrition rates. THESEUS was prospectively registered on the ISRCTN registry: ISRCTN69985145. RESULTS: The recruitment target of 150 participants was met after 18 months, in July 2021, with two pauses due to the COVID-19 pandemic. Baseline demographics reflected the HS secondary care population: average age 36 years, 81% female, 20% non-White, 64% current or ex-smokers, 86% body mass index ≥ 25, 68% with moderate disease, 19% with severe disease and 13% with mild disease. Laser was the intervention with the highest proportion (69%) of participants eligible and willing to receive treatment, then deroofing (58%), conventional surgery (54%), clindamycin and rifampicin (44%), and doxycycline (37%). Laser was ranked first choice by the greatest proportion of participants (41%). Attrition rates were 11% and 17% after 3 and 6 months, respectively. Concordance with doxycycline was 52% after 3 months due to lack of efficacy, participant choice and adverse effects. Delays with procedural interventions were common, with only 43% and 26% of participants starting laser and deroofing, respectively, after 3 months. Uptake of conventional surgery was too small to characterize the intervention. Switching treatment was uncommon and there were no serious adverse events. CONCLUSIONS: THESEUS has established laser treatment and deroofing for HS in the UK and demonstrated their popularity with patients and clinicians for future RCTs.

Analysis of Escherichia coli O157 strains in cattle and humans between Scotland and England & Wales: implications for human health.

For the last two decades, the human infection frequency of Escherichia coli O157 (O157) in Scotland has been 2.5-fold higher than in England and Wales. Results from national cattle surveys conducted in Scotland and England and Wales in 2014/2015 were combined with data on reported human clinical cases from the same time frame to determine if strain differences in national populations of O157 in cattle could be associated with higher human infection rates in Scotland. Shiga toxin subtype (Stx) and phage type (PT) were examined within and between host (cattle vs human) and nation (Scotland vs England and Wales). For a subset of the strains, whole genome sequencing (WGS) provided further insights into geographical and host association. All three major O157 lineages (I, II, I/II) and most sub-lineages (Ia, Ib, Ic, IIa, IIb, IIc) were represented in cattle and humans in both nations. While the relative contribution of different reservoir hosts to human infection is unknown, WGS analysis indicated that the majority of O157 diversity in human cases was captured by isolates from cattle. Despite comparable cattle O157 prevalence between nations, strain types were localized. PT21/28 (sub-lineage Ic, Stx2a+) was significantly more prevalent in Scottish cattle [odds ratio (OR) 8.7 (2.3-33.7; P<0.001] and humans [OR 2.2 (1.5-3.2); P<0.001]. In England and Wales, cattle had a significantly higher association with sub-lineage IIa strains [PT54, Stx2c; OR 5.6 (1.27-33.3); P=0.011] while humans were significantly more closely associated with sub-lineage IIb [PT8, Stx1 and Stx2c; OR 29 (4.9-1161); P<0.001]. Therefore, cattle farms in Scotland were more likely to harbour Stx2a+O157 strains compared to farms in E and W (P<0.001). There was evidence of limited cattle strain migration between nations and clinical isolates from one nation were more similar to cattle isolates from the same nation, with sub-lineage Ic (mainly PT21/28) exhibiting clear national association and evidence of local transmission in Scotland. While we propose the higher rate of O157 clinical cases in Scotland, compared to England and Wales, is a consequence of the nationally higher level of Stx2a+O157 strains in Scottish cattle, we discuss the multiple additional factors that may also contribute to the different infection rates between these nations.

Genome structural variation in Escherichia coli O157:H7.

The human zoonotic pathogen Escherichia coli O157:H7 is defined by its extensive prophage repertoire including those that encode Shiga toxin, the factor responsible for inducing life-threatening pathology in humans. As well as introducing genes that can contribute to the virulence of a strain, prophage can enable the generation of large-chromosomal rearrangements (LCRs) by homologous recombination. This work examines the types and frequencies of LCRs across the major lineages of the O157:H7 serotype. We demonstrate that LCRs are a major source of genomic variation across all lineages of E. coli O157:H7 and by using both optical mapping and Oxford Nanopore long-read sequencing prove that LCRs are generated in laboratory cultures started from a single colony and that these variants can be recovered from colonized cattle. LCRs are biased towards the terminus region of the genome and are bounded by specific prophages that share large regions of sequence homology associated with the recombinational activity. RNA transcriptional profiling and phenotyping of specific structural variants indicated that important virulence phenotypes such as Shiga-toxin production, type-3 secretion and motility can be affected by LCRs. In summary, E. coli O157:H7 has acquired multiple prophage regions over time that act to continually produce structural variants of the genome. These findings raise important questions about the significance of this prophage-mediated genome contingency to enhance adaptability between environments.

Prevalence and Epidemiology of Non-O157 Escherichia coli Serogroups O26, O103, O111, and O145 and Shiga Toxin Gene Carriage in Scottish Cattle, 2014-2015.

Cattle are a reservoir for Shiga toxin-producing Escherichia coli (STEC), zoonotic pathogens that cause serious clinical disease. Scotland has a higher incidence of STEC infection in the human population than the European average. The aim of this study was to investigate the prevalence and epidemiology of non-O157 serogroups O26, O103, O111, and O145 and Shiga toxin gene carriage in Scottish cattle. Fecal samples (n = 2783) were collected from 110 herds in 2014 and 2015 and screened by real-time PCR. Herd-level prevalence (95% confidence interval [CI]) for O103, O26, and O145 was estimated as 0.71 (0.62, 0.79), 0.43 (0.34, 0.52), and 0.23 (0.16, 0.32), respectively. Only two herds were positive for O111. Shiga toxin prevalence was high in both herds and pats, particularly for stx2 (herd level: 0.99; 95% CI: 0.94, 1.0). O26 bacterial strains were isolated from 36 herds on culture. Fifteen herds yielded O26 stx-positive isolates that additionally harbored the intimin gene; six of these herds shed highly pathogenic stx2-positive strains. Multiple serogroups were detected in herds and pats, with only 25 herds negative for all serogroups. Despite overlap in detection, regional and seasonal effects were observed. Higher herd prevalence for O26, O103, and stx1 occurred in the South West, and this region was significant for stx2 at the pat level (P = 0.015). Significant seasonal variation was observed for O145 prevalence, with the highest prevalence in autumn (P = 0.032). Negative herds were associated with Central Scotland and winter. Herds positive for all serogroups were associated with autumn and larger herd size and were not housed at sampling.IMPORTANCE Cattle are reservoirs for Shiga toxin-producing Escherichia coli (STEC), bacteria shed in animal feces. Humans are infected through consumption of contaminated food or water and by direct contact, resulting in serious disease and kidney failure in the most vulnerable. The contribution of non-O157 serogroups to STEC illness was underestimated for many years due to the lack of specific tests. Recently, non-O157 human cases have increased, with O26 STEC of particular note. It is therefore vital to investigate the level and composition of non-O157 in the cattle reservoir and to compare them historically and by the clinical situation. In this study, we found cattle prevalence high for toxin, as well as for O103 and O26 serogroups. Pathogenic O26 STEC were isolated from 14% of study herds, with toxin subtypes similar to those seen in Scottish clinical cases. This study highlights the current risk to public health from non-O157 STEC in Scottish cattle.

The British E. coli O157 in cattle study (BECS): factors associated with the occurrence of E. coli O157 from contemporaneous cross-sectional surveys.

BACKGROUND: Escherichia coli O157 is a bacterial pathogen associated with severe disease in humans for which cattle are an important reservoir of infection. The identification of possible risk factors for infection in cattle could facilitate the development of control strategies and interventions to mitigate the risk to human health. The purpose of this study was to utilize data collected in 2014-2015 during the two contemporaneous cross-sectional surveys of the British E. coli O157 in Cattle Study (BECS) to investigate potential risk factors for E. coli O157 status in cattle destined for the food chain. RESULTS: In the England & Wales survey only one variable, herd size, was associated with the outcome farm-level E. coli O157 positive status. The odds increased for each additional animal in the herd. In the Scotland survey, as well as a measure of herd size (the number of cattle aged 12-30 months), having brought breeding females on to the farm in the last year also increased the odds, whereas farms sampled in spring were less likely to be positive compared to those sampled in autumn. On the positive farms, in both surveys, an increase in the proportion of pats positive for E. coli O157 was associated with animals being housed at the time of sampling. However, the effect of housing on pat-level prevalence within positive groups was lower on farms from England & Wales than from Scotland (OR 0.45 (95% C.I. 0.24-0.86)). CONCLUSION: For the first time, factors associated with farm-level E. coli O157 status have been investigated in two contemporaneous surveys with comparable study design. Although factors associated with farm-level E. coli O157 status differed between the two surveys, one consistent factor was an association with a measure of herd size. Factors associated with the proportion of E. coli O157 positive pats within a positive farm were similar in both surveys but differed from those associated with farm-level status. These findings raise the hypothesis that measures to protect public health by reducing the risk from cattle may need to be tailored, rather than by assuming that a GB-wide protocol is the best approach.

Co-infection with Fasciola hepatica may increase the risk of Escherichia coli O157 shedding in British cattle destined for the food chain.

Escherichia coli O157 is a zoonotic bacterium that can cause haemorrhagic diarrhoea in humans and is of worldwide public health concern. Cattle are considered to be the main reservoir for human infection. Fasciola hepatica is a globally important parasite of ruminant livestock that is known to modulate its host's immune response and affect susceptibility to bacterial pathogens such as Salmonella Dublin. Shedding of E. coli O157 is triggered by unknown events, but the immune system is thought to play a part. We investigated the hypothesis that shedding of E. coli O157 is associated with F. hepatica infection in cattle. Three hundred and thirty four cattle destined for the food chain, from 14 British farms, were tested between January and October 2015. E. coli O157 was detected by immunomagnetic separation and bacterial load enumerated. F. hepatica infection status was assessed by copro-antigen ELISA. A significant association (p=0.01) was found between the log percent positivity (PP) of the F. hepatica copro-antigen ELISA and E. coli O157 shedding when the fixed effects of day of sampling and the age of the youngest animal in the group, plus the random effect of farm were adjusted for. The results should be interpreted cautiously due to the lower than predicted level of fluke infection in the animals sampled. Nevertheless these results indicate that control of F. hepatica infection may have an impact on the shedding of E. coli O157 in cattle destined for the human food chain.

Pathogenic potential to humans of bovine Escherichia coli O26, Scotland.

Escherichia coli O26 and O157 have similar overall prevalences in cattle in Scotland, but in humans, Shiga toxin-producing E. coli O26 infections are fewer and clinically less severe than E. coli O157 infections. To investigate this discrepancy, we genotyped E. coli O26 isolates from cattle and humans in Scotland and continental Europe. The genetic background of some strains from Scotland was closely related to that of strains causing severe infections in Europe. Nonmetric multidimensional scaling found an association between hemolytic uremic syndrome (HUS) and multilocus sequence type 21 strains and confirmed the role of stx(2) in severe human disease. Although the prevalences of E. coli O26 and O157 on cattle farms in Scotland are equivalent, prevalence of more virulent strains is low, reducing human infection risk. However, new data on E. coli O26-associated HUS in humans highlight the need for surveillance of non-O157 enterohemorrhagic E. coli and for understanding stx(2) phage acquisition.

Prevalence of Escherichia coli O157: H7 and serogroups O26, O103, O111 and O145 in sheep presented for slaughter in Scotland.

Sheep have been proposed as a source of human verocytotoxigenic Escherichia coli infection on a number of occasions but few prevalence studies have focused on identifying rates of carriage of these pathogens in this species. The purpose of this work was to establish the frequency of excretion of E. coli of serogroups O157, O26, O103, O111 and O145 in sheep presented for slaughter in Scotland and to examine their carriage of known virulence determinants. The study involved microbiological isolation of E. coli from 1082 sheep presented for slaughter in four Scottish abattoirs between July 2005 and June 2006. Using faecal enrichment and immunomagnetic separation, the isolation rate from these samples was 3.4 % for E. coli serogroup O157, 5.2 % for E. coli serogroup O26, 2.3 % for E. coli serogroup O103 and 0.1 % for E. coli serogroup O145. E. coli O111 was not isolated. In the last month of testing, which coincided with sorbitol-fermenting E. coli O157 (SFO157) cases in children in Scotland, all 83 recta received were screened and tested negative for SFO157 strains. The study found no verocytotoxin-positive strains amongst the E. coli serogroup O103 or O145 isolates. Verocytotoxin-positive strains were identified amongst isolates of E. coli serotypes O157 : H7 and O26 : H11. E. coli O157 : H7 was not isolated from samples collected between January and March, a statistically significant drop (P<0.001) in mean shedding relative to other months. There was evidence (P = 0.003) of higher shedding of O157 in adults and hoggs than in lambs. E. coli O26 : H11 was isolated throughout the year, with a statistically significant peak in shedding in the third quarter (P = 0.003). The results showed that sheep presented for slaughter in Scotland may carry strains of E. coli, particularly of serogroups O157 and O26, which can be presumed to have potential to cause human infection. They did not support a hypothesis that human cases of E. coli O157 : H7 are higher in any particular Scottish region as a direct consequence of a higher rate of faecal carriage in sheep in that region.

Use of citrate adonitol agar as a selective medium for the isolation of Escherichia fergusonii from a captive reindeer herd.

Escherichia fergusonii is an emerging potentially zoonotic organism which has been recovered from a broad range of human and animal sources. Efforts to recover E. fergusonii from mixed flora hitherto however have been constrained by the lack of a suitable selective medium for its isolation. This paper reports for the first time the recovery of E. fergusonii from reindeer carcases in a wildlife park and the use of citrate adonitol agar to selectively screen for the presence of this organism in faecal samples from further animals in the park, and reindeer in their natural habitat in Norway.

Upper gastrointestinal tolerability of alendronate sodium monohydrate 10 mg once daily in postmenopausal women: a 12-week, randomized, double-blind, placebo-controlled, exploratory study.

BACKGROUND: The dissolution profiles of generic oral bisphosphonate alendronate (ALN) sodium for the treatment of postmenopausal osteoporosis differ by formulation, suggesting potential differences in the risk for upper gastrointestinal (GI) irritation. OBJECTIVE: This study compared the tolerability profile of ALN monohydrate with that of placebo, with a focus on upper GI irritation, in postmenopausal women with osteoporosis. METHODS: This multicenter, double-blind, placebo-controlled estimation study enrolled postmenopausal women with osteoporosis. Patients were randomized in a 2:1 ratio to receive ALN monohydrate 10 mg or placebo once daily for 12 weeks. Tolerability was monitored throughout the study and up to 14 days after administration of the final dose. Primary end points were the proportions of patients with upper GI adverse events (AEs); upper GI AEs that were rated as serious or study drug related or that led to study discontinuation; and esophageal AEs. Between-treatment differences and associated 95% CIs were assessed using the Wilson score method. RESULTS: Of 438 patients who were randomized, 367 (mean age, 65.5 years; history of osteoporotic fracture, 6.8%; ALN monohydrate, 237; placebo, 130) completed the study. The proportion of patients with a history of upper GI disorders at baseline was numerically greater in the ALN monohydrate group than in the placebo group (117 [40.2%] and 45 [30.6%], respectively). The proportions of patients with active baseline upper GI disease were 83 (28.5%) and 30 (20.4%) in the ALN monohydrate and placebo groups, respectively. The proportions of patients who experienced an upper GI AE during the study period were 66 (22.7%) and 30 (20.4%) (95% CI, -6.2 to 10.0). The proportions of patients with upper GI AEs that were rated as serious or study drug related or that led to study discontinuation were 20.3% and 12.9% (95% CI, -0.3% to 14.1%). Three serious AEs in the active-treatment group (breast cancer, 2; wrist fracture, 1) were not considered related to the study drug, nor was the 1 serious AE in the placebo group (wrist fracture). One patient (ALN monohydrate) had an esophageal AE (nonserious spasm). Approximately 8% of patients who received ALN monohydrate reported dyspepsia, compared with none who received placebo. Within each treatment group, the rates of upper GI AEs were numerically higher in patients with a history of upper GI disease. CONCLUSIONS: In these postmenopausal women who received ALN monohydrate or placebo, upper GI AEs were common (20.4%-22.7%). The proportion of patients who experienced upper GI AEs considered drug related or that led to discontinuation was appar- ently greater with ALN monohydrate compared with placebo.

Lack of effect of aprepitant or its prodrug fosaprepitant on QTc intervals in healthy subjects.

BACKGROUND: A single 115-mg dose of fosaprepitant, the IV prodrug of the NK(1) receptor antagonist aprepitant, is bioequivalent to a 125-mg dose of oral aprepitant. Thus far, fosaprepitant/aprepitant has not shown a meaningful effect on QTc intervals; in this study, we sought to confirm these findings. METHODS: This double-blind, active-controlled, randomized, three-treatment, three-period, crossover study in healthy young subjects evaluated the effect of a 200-mg dose of fosaprepitant on QTc prolongation. In each period, subjects received 400 mg moxifloxacin per os, 200 mg fosaprepitant IV, or placebo in randomized sequence. The effect of fosaprepitant on QTc interval was assessed by 12-lead electrocardiograms (ECGs). The baseline value for QTc interval for each subject during each period was defined as the average of five replicate baseline QTc intervals extracted from predose ECGs. ECGs were performed at predose, 2, 5, 10, 15, 20, 30, 45 min; and 1, 1.5, 2, 3, 4, 6, and 8 h postinfusion. Values for individual QTc change from baseline were evaluated in a repeated-measures mixed model appropriate for a crossover design. A two-sided 90% confidence interval (CI) for the true difference in QTc interval change from baseline at each timepoint was calculated for fosaprepitant versus placebo and for moxifloxacin versus placebo. RESULTS: After fosaprepitant 200-mg administration, the mean (95% CI) QTc interval change from baseline at T(max) was -1.45 (-4.67 to 1.77) ms, and the placebo-corrected mean (90% CI) QTc interval change from baseline was -1.37 (-4.78 to 2.05) ms. Neither was statistically significant at alpha = 0.05. After 400 mg moxifloxacin administration, the mean (95% CI) QTc interval change from baseline at 2 h was 9.71 (6.49-12.93) ms, and the placebo-corrected mean (90% CI) QTc interval change from baseline at moxifloxacin T(max) was 10.50 (7.09-13.92) ms. Both were statistically significant at alpha = 0.05. The maximum aprepitant concentration after fosaprepitant 200 mg administration was 6300 ng/mL (approximately twofold, fourfold, and ninefold higher than that observed historically with fosaprepitant 115 mg [3095 ng/mL], aprepitant 125 mg [1600 ng/mL], and aprepitant 40 mg [675 ng/mL]). CONCLUSIONS: In subjects receiving fosaprepitant 200 mg, no clinically meaningful increases in QTc were seen at any timepoint, whereas after moxifloxacin 400 mg, increases were observed at the approximate T(max) of moxifloxacin and additional timepoints. The lack of QTc increase at this high dose of fosaprepitant and resulting aprepitant plasma exposures support the expectation that clinical doses of fosaprepitant or aprepitant will not be associated with significant QTc prolongation.

Predictors of adherence to triptans: factors of sustained vs lapsed users.

OBJECTIVE: The present study was conducted to identify factors that predict adherence to triptans by migraine patients. BACKGROUND: Triptans have demonstrated efficacy for acute migraine yet many migraine sufferers discontinue their use. DESIGN AND METHODS: A survey study was conducted using 785 subjects (390 health maintenance organizations [HMO] and 395 non-HMO). Of those, 586 were sustained users of triptans (defined by at least 1 refill within the past year), and 199 were classified as lapsed users (ie, individuals who had 0 refills in the past year). Groups were compared on a variety of measures including a comprehensive Migraine Survey that included items related to efficacy and adverse events associated with the patient's current medication, as well as the Headache Impact Test (HIT)-6 and Migraine Disability Assessment Score (MIDAS) questionnaires. Data were analyzed with multivariate analysis of variance and stepwise multiple regression. RESULTS: Sustained users of triptans were significantly more satisfied with their medication, confident in the medication's ability to control headache, and reported control of migraine with fewer doses of medication. Sustained users also switched triptans products significantly less often than lapsed users, and reported greater benefit from triptan intervention in restoring normal daily functions, including improved cognitive ability, compared with lapsed users' ratings of their nontriptan medication. More lapsed users than sustained users reported adverse events associated with past triptan use. Results from multiple and logistic regression analyses correctly classified 95% of sustained users and identified the most significant predictors for sustained use as: satisfaction and belief in medication, reliability of response, effectiveness in rapidly restoring normal levels of productivity, and fewer doses of medication for resolving an attack. The HIT-6 and MIDAS distinguished between sustained and lapsed triptan users on days unable to do household work and missed family and social events. CONCLUSIONS: Predictors of adherence to triptans included satisfaction and confidence in triptans' ability to stop the migraine and associated symptoms and to return the individual to normal functioning. The findings suggest that lapsed users may not be receiving optimal treatment, and that if their past response to triptans was a consequence of inadequate education, they may benefit from additional education on proper use of triptans.

Migraine strikes study: factors in patients' decision to treat early.

To describe factors associated with early treatment of migraine, and to examine reasons patients do not treat early, this cross-sectional observational study email-recruited migraineurs >or= 18-years-old who were currently prescribed acute migraine medication. Within 24 h of migraine resolution, eligible patients completed an online migraine strikes questionnaire which addressed pain severity, associated symptoms, and other variables including reasons for not treating early. Results reported were descriptive. Among 1,044 evaluable patients, early treatment was significantly associated with several factors such as leisure activity at onset (OR 1.32, P=0.010), photophobia (OR 1.39, P=0.013), diagnosis of migraine with aura (OR 1.36, P=0.004), and other factors. Among 840 patients who reported wanting to treat earlier desire to reserve medication for a severe migraine was the most common reason given for not doing so (51.2%). Overcoming these factors may facilitate earlier migraine treatment.

Aprepitant in adolescent patients for prevention of chemotherapy-induced nausea and vomiting: a randomized, double-blind, placebo-controlled study of efficacy and tolerability.

BACKGROUND: The neurokinin-1 receptor antagonist aprepitant, plus a 5HT3 antagonist and corticosteroid is well-tolerated and effective in preventing chemotherapy-induced nausea and vomiting in adults but has not been formally assessed in adolescents. PROCEDURE: Patients age 11-19 years old receiving emetogenic chemotherapy were randomized 2:1 to aprepitant triple therapy (aprepitant [A] 125 mg p.o., dexamethasone [D] 8 mg p.o., and ondansetron [O] 0.15 mg/kg i.v. t.i.d. day 1; A 80 mg, D 4 mg, and O 0.15 mg/kg t.i.d. day 2; A 80 mg and D 4 mg day 3; and D 4 mg day 4) or a control regimen (D 16 mg and O 0.15 mg/kg t.i.d. day 1; D 8 mg and O 0.15 mg/kg t.i.d. day 2; and D 8 mg days 3 and 4). The primary endpoint was the difference in drug-related adverse events during and for 14 days following treatment. Efficacy and aprepitant pharmacokinetics were assessed. RESULTS: Baseline characteristics were similar between aprepitant (N = 28) and control (N = 18) groups. Febrile neutropenia was more frequent in the aprepitant group (25% vs. 11.1%). Complete response (CR) rates were 35.7% for aprepitant triple therapy versus 5.6% for the control group. Mean plasma aprepitant AUC(0-24 hr) and C(max) on day 1 and mean trough concentrations on days 2 and 3 were consistently lower compared to historical data obtained from healthy adults; however, the differences were not clinically significant. CONCLUSION: Aprepitant triple therapy was generally well tolerated; CR were greater with aprepitant, although not statistically significant. Pharmacokinetics suggest that the adult dosing regimen is appropriate for adolescents.

Vascular perfusion chilling of red meat carcasses - A feasibility study.

Meat carcasses must be chilled to below 7°C before leaving the slaughterhouse. Typically this is done by passing cold air over the surfaces of eviscerated and de-hided carcasses. This surface cooling can take many hours to reduce centre temperatures to below 7°C. In vascular perfusion chilling (VPC), a cold fluid is circulated through the intact vascular system, offering significant reductions in cooling time. This paper describes a small feasibility study to evaluate vascular perfusion techniques for rapid chilling of lamb carcasses using a proprietary Flo-ice(™) system. This produces pumpable ice slurries containing very fine ice particles, suitable for circulating through vascular systems. VPC was found to be capable of rapid initial reduction of carcass temperatures in comparison with air chilling (mean times to 20°C in deep legs were reduced from 2.6 to 1.3h, which was significantly different at P<0.05). In all cases however, uptake of perfusate into the carcasses occurred. This limited the duration of the perfusion treatment and as a result restricted the period of enhanced cooling. Samples from carcasses treated with VPC were lighter (P<0.05, with mean measured L value increasing from 43.4 to 46.8) and more yellow (P<0.05, with mean measured b value increasing from 6.7 to 7.9) than samples from conventionally chilled carcasses, and had lower shear force values when cooked (P<0.05, with mean force reducing from 10.0 to 6.8kg). This was most probably due to the added water in the meat. Microbial quality of the meat was not significantly affected by the perfusion treatments.

Pathogenic potential of emergent sorbitol-fermenting Escherichia coli O157:NM.

Non-sorbitol-fermenting (NSF) Escherichia coli O157:H7 is the primary Shiga toxin-producing E. coli (STEC) serotype associated with human infection. Since 1988, sorbitol-fermenting (SF) STEC O157:NM strains have emerged and have been associated with a higher incidence of progression to hemolytic-uremic syndrome (HUS) than NSF STEC O157:H7. This study investigated bacterial factors that may account for the increased pathogenic potential of SF STEC O157:NM. While no evidence of toxin or toxin expression differences between the two O157 groups was found, the SF STEC O157:NM strains adhered at significantly higher levels to a human colonic cell line. Under the conditions tested, curli were shown to be the main factor responsible for the increased adherence to Caco-2 cells. Notably, 52 of 66 (79%) European SF STEC O157:NM strains tested bound Congo red at 37 degrees C and this correlated with curli expression. In a subset of strains, curli expression was due to increased expression from the csgBAC promoter that was not always a consequence of increased csgD expression. The capacity of SF STEC O157:NM strains to express curli at 37 degrees C may have relevance to the epidemiology of human infections as curliated strains could promote higher levels of colonization and inflammation in the human intestine. In turn, this could lead to increased toxin exposure and an increased likelihood of progression to HUS.

Preventing postoperative nausea and vomiting: post hoc analysis of pooled data from two randomized active-controlled trials of aprepitant.

OBJECTIVE: Compared with the 5HT(3) antagonist ondansetron, the NK(1) antagonist aprepitant has been shown in two double-blind trials to provide greater protection against postoperative vomiting and comparable or greater control of nausea. Post hoc analyses of pooled data from these trials were performed to more fully characterize the efficacy profile of aprepitant in terms of nausea and use of rescue therapy. RESEARCH DESIGN AND METHODS: Patients (n = 1599) scheduled for major surgery under general anesthesia (primarily gynecological surgery) were assigned to receive a preoperative dose of aprepitant 40 mg PO, 125 mg PO, or ondansetron 4 mg IV. in two randomized, double-blind, clinical trials. MAIN OUTCOME MEASURES: Post-surgery vomiting episodes, use of rescue therapy, and nausea severity (verbal rating scale). RESULTS: In the 24 hours after surgery, aprepitant 40 mg was more effective than ondansetron for all five endpoints evaluated: (1) no significant nausea (56.4% vs. 48.1%); (2) no nausea (39.6% vs. 33.1%); (3) no vomiting (86.7% vs. 72.4%); (4) no nausea and no vomiting (38.3% vs. 31.4%); and (5) no nausea, no vomiting, and no use of rescue (37.9% vs. 31.2%) (p < 0.035 for the odds ratio for each comparison). Numerically more patients receiving aprepitant 125 mg also achieved these endpoints compared with ondansetron. CONCLUSIONS: These post hoc analyses confirm the favorable efficacy profile of aprepitant for the prevention of post operative nausea and vomiting.

Tolerability of fosaprepitant and bioequivalency to aprepitant in healthy subjects.

Fosaprepitant is an intravenous formulation of aprepitant, an oral NK1 antagonist used to prevent chemotherapy-induced nausea and vomiting. This randomized study was designed to evaluate fosaprepitant in polysorbate 80 vehicle for tolerability and bioequivalency to aprepitant. Tolerability was assessed by physical and laboratory examinations and adverse events. Plasma collected for 72 hours was assayed for aprepitant and fosaprepitant. Analysis of variance models were applied to natural log-transformed aprepitant area under the curve (AUC) data. Fosaprepitant up to 150 mg (1 mg/mL) was generally well tolerated. Fosaprepitant 115 mg was AUC bioequivalent to aprepitant 125 mg; the 90% confidence interval for the geometric mean ratio of aprepitant AUC for fosaprepitant 115 mg/aprepitant 125 mg fell within prespecified equivalence bounds of 0.80 to 1.25.