Preoperative anthropomorphic radiographic measurements can predict postoperative pancreatic fistula formation following pancreatoduodenectomy.

BACKGROUND: Postoperative pancreatic fistulae (POPF) are a major contributing factor to pancreatoduodenectomy-associated morbidity. Established risk calculators mostly rely on subjective or intraoperative assessments. We hypothesized that various objective preoperatively determined computed tomography (CT) measurements could predict POPF as well as validated models and allow for more informed operative consent in high-risk patients. METHODS: Patients undergoing elective pancreatoduodenectomies between January 2013 and April 2018 were identified in a prospective database. Comparative statistical analyses and multivariable logistic regression models were generated to predict POPF development. Model performance was tested with receiver operating characteristics (ROC) curves. Pancreatic neck attenuation (Hounsfield units) was measured in triplicate by pancreatic protocol CT (venous phase, coronal plane) anterior to the portal vein. A pancreatic density index (PDI) was created to adjust for differences in contrast timing by dividing the mean of these measurements by the portal vein attenuation. Total areas of subcutaneous fat and skeletal muscle were calculated at the L3 vertebral level on axial CT. Pancreatic duct (PD) diameter was determined by CT. RESULTS: In the study period 220 patients had elective pancreatoduodenectomies with 35 (16%) developing a POPF of any grade. Multivariable regression analysis revealed that demographics (age, sex, and race) were not associated with POPF, yet patients resected for pancreatic adenocarcinoma or chronic pancreatitis were less likely to develop a POPF (10 vs. 24%; p = 0.004). ROC curves were created using various combinations of gland texture, body mass index, skeletal muscle index, sarcopenia, PDI, PD diameter, and subcutaneous fat area indexed for height (SFI). A model replacing gland texture with SFI and PDI (AUC 0.844) had similar predictive performance as the established model (p = 0.169). CONCLUSION: A combination of preoperative objective CT measurements can adequately predict POPF and is comparable to established models relying on subjective intraoperative variables. Validation in a larger dataset would allow for better preoperative stratification of high-risk patients and improve informed consent among this patient population.

Occurrence of a human-associated microbial source tracking marker and its relationship with faecal indicator bacteria in an urban estuary.

One of the main impacts of urban sprawl in rapidly growing countries has been contamination of coastal environments by waterborne pathogens, posing a critical risk to ecosystem and human health. Microbial source tracking (MST) has been a robust tool to identify the origin of these pathogens globally. This study compared the occurrence of a human-associated Bacteroides marker (BT-α) with faecal indicator bacteria (FIB) in an urban estuary (Golden Horn, Istanbul, Turkey). Faecal coliform (culture method), enterococci (both culture and qPCR method) concentrations and physicochemical variables were compared with the BT-α concentrations in monthly collected samples for a year (n = 108). Enterococci concentrations detected by culture and qPCR were positively correlated (r = 0·86, P < 0·01) suggesting that qPCR can be an alternative method for monitoring. BT-α marker was positive for 30% of the samples and positively correlated with enterococci (r = 0·61 and r = 0·64 for culture and qPCR methods respectively, P < 0·01). Rainfall had a moderate positive correlation with all faecal/MST indicators suggesting combined sewer overflows also severely impacted estuarine water quality. The high FIB and BT-α concentrations at upper estuary suggested that faecal pollution mainly originated from the peri-urban settlements around two creeks entering the estuary.

Persistence analysis of poliovirus on three different types of fomites.

AIMS: The goal of this study was to explore various models for describing viral persistence (infectivity) on fomites and identify the best fit models. METHODS AND RESULTS: The persistence of poliovirus over time was studied on three different fomite materials: steel, cotton and plastic. Known concentrations of poliovirus type 1 were applied to the surface coupons in an indoor environment for various lengths of time. Viruses were recovered from the surfaces by vortexing in phosphate buffer. Seven different mathematical models of relative persistence over time were fit to the data, and the preferred model for each surface was selected based on the Bayesian information criterion. CONCLUSIONS: While the preferred model varied by fomite type, the virus showed a rapid initial decay on all of the fomite types, followed by a transition to a more gradual decay after about 4-8 days. Estimates of the time for 99% reduction ranged from 81 h for plastic to 143 h for cotton. A 6 log reduction of recoverable infectivity of poliovirus did not occur during the 3-week duration of the experiment for any of the fomites. SIGNIFICANCE AND IMPACT OF THE STUDY: In protected indoor environments poliovirus can remain infective for weeks. The models identified by this study can be used in risk assessments to identify appropriate strategies for managing this risk.

Risk assessment of noroviruses and human adenoviruses in recreational surface waters.

In the interest of public health and safety, this study aimed to quantify risks associated with the presence of noroviruses (NoV) and human adenoviruses (HAdV) in an urban catchment area in Singapore. Enteric viruses were quantified using QPCR. NoV were more prevalent in water samples than HAdV, and presented higher associated illness risks across all exposure scenarios. For primary contact recreation of adults and children, mean probability of illness were 0.0061 and 0.0089 for NoV, and 0.0028 and 0.0048 for HAdV. For secondary contact recreation, mean probability of illness were 0.0016 for NoV and 0.00068 for HAdV. Therefore, owing to their prevalence and associated risks, NoV are better suited as reference pathogens in recreational waters in Singapore.

Alternative fecal indicators and their empirical relationships with enteric viruses, Salmonella enterica, and Pseudomonas aeruginosa in surface waters of a tropical urban catchment.

The suitability of traditional microbial indicators (i.e., Escherichia coli and enterococci) has been challenged due to the lack of correlation with pathogens and evidence of possible regrowth in the natural environment. In this study, the relationships between alternative microbial indicators of potential human fecal contamination (Bacteroides thetaiotaomicron, Methanobrevibacter smithii, human polyomaviruses [HPyVs], and F+ and somatic coliphages) and pathogens (Salmonella spp., Pseudomonas aeruginosa, rotavirus, astrovirus, norovirus GI, norovirus GII, and adenovirus) were compared with those of traditional microbial indicators, as well as environmental parameters (temperature, conductivity, salinity, pH, dissolved oxygen, total organic carbon, total suspended solids, turbidity, total nitrogen, and total phosphorus). Water samples were collected from surface waters of urban catchments in Singapore. Salmonella and P. aeruginosa had significant positive correlations with most of the microbial indicators, especially E. coli and enterococci. Norovirus GII showed moderately strong positive correlations with most of the microbial indicators, except for HPyVs and coliphages. In general, high geometric means and significant correlations between human-specific markers and pathogens suggest the possibility of sewage contamination in some areas. The simultaneous detection of human-specific markers (i.e., B. thetaiotaomicron, M. smithii, and HPyVs) with E. coli and enterococcus supports the likelihood of recent fecal contamination, since the human-specific markers are unable to regrow in natural surface waters. Multiple-linear-regression results further confirm that the inclusion of M. smithii and HPyVs, together with traditional indicators, would better predict the occurrence of pathogens. Further study is needed to determine the applicability of such models to different geographical locations and environmental conditions.

Cyclic hydrostatic pressure stimulates enhanced bone development in the foetal chick femur in vitro.

Mechanical loading of bone and cartilage in vivo results in the generation of cyclic hydrostatic forces as bone compression is transduced to fluid pressure in the canalicular network and the joint synovium. It has therefore been suggested that hydrostatic pressure is an important stimulus by which osteochondral cells and their progenitors sense and respond to mechanical loading in vivo. In this study, hydrostatic pressure regimes of 0-279kPa at 0.005-2Hz were applied to organotypically cultured ex vivo chick foetal femurs (e11) for 1hour per day in a custom designed bioreactor for 14days and bone formation assessed by X-ray microtomography and qualified by histology. We found that the mineralised portion of the developing femur cultured under any cyclic hydrostatic pressure regime was significantly larger and/or denser than unstimulated controls but that constant (non-cycling) hydrostatic pressure had no effect on bone growth. Further experiments showed that the increase in bone formation was directly proportional to stimulation frequency (R(2)=0.917), but independent of the magnitude of the pressure applied, whilst even very low frequencies of stimulation (0.005Hz) had significant effects on bone growth. Expression of Type-II collagen in both epiphyses and diaphysis was significantly upregulated (1.48-fold and 1.95-fold respectively), together with osteogenic genes (osteonectin and osteopontin) and the osteocyte maturation marker CD44. This work demonstrates that cyclic hydrostatic pressure promotes bone growth and mineralisation in a developmental model and supports the hypothesis that hydrostatic forces play an important role in regulating bone growth and remodelling in vivo.

Evaluation of the host specificity of Bacteroides thetaiotaomicron alpha-1-6, mannanase gene as a sewage marker.

UNLABELLED: The specificity of a short fragment functional gene marker (alpha-1-6, mannanase) in Bacteroides thetaiotaomicron was compared with two other Bacteroidales markers used for identifying sewage as the source of pollution in water. A total of 11 different animal species and 230 faecal samples were tested using quantitative polymerase chain reaction. The results showed that the alpha-1-6, mannanase marker had high specificity (0·97). Limited cross-reactivity was found in swine, gull and cat faeces with copy numbers close to detection limit. Positives were detected in all bovine and sheep faeces tested for the Human-Bac1 marker. The human-specific alpha-1-6, mannanase marker showed greater specificity (0·97) than the HF 183 Bacteroides PCR marker (0·71) and the Human-Bac1 (qPCR) marker. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first study that compares Bacteroides thetaiotaomicron alpha-1-6, mannanase marker with other markers. Our study showed that this marker has strong potential to be used as an indicator for sewage pollution in water.

Occurrence of adenovirus and other enteric viruses in limited-contact freshwater recreational areas and bathing waters.

AIMS: The goal of this study was to characterize enteric virus concentrations and their infectivity in a variety of limited-contact recreation and bathing waters, including Great Lakes beaches, inland lakes, rivers, and an effluent-dominated urban waterway. Additionally, we evaluated associations between point sources of human faecal pollution and enterovirus and adenovirus presence and concentrations. METHODS AND RESULTS: Quantitative polymerase chain reaction (qPCR) and two cell culture lines were used to identify and quantify viruses in water samples. The presence of human adenoviruses F was strongly associated with effluent-dominated waters (odds ratio 6·1, confidence interval 2·3, 15·7), as was adenovirus concentration; though, neither enterovirus presence nor concentration was associated with an effluent source. Samples with high concentrations of qPCR targets all tested positive by cell culture on both cell lines, although qPCR target concentrations were not correlated with culture values. CONCLUSIONS: Adenovirus was strongly associated with point sources of human faecal pollution while enterovirus was not, indicating that adenovirus measured by qPCR is a better target than enterovirus for identifying wastewater discharges in recreational freshwaters. SIGNIFICANCE AND IMPACT OF THE STUDY: The development of monitoring for enteric human viral pathogens at recreational waters should include adenovirus testing. Further research is needed to interpret the results of qPCR testing in relationship to the presence of infectious viruses using cell culture.

Cladophora in the Great Lakes: impacts on beach water quality and human health.

Cladophora in the Great Lakes grows rapidly during the warm summer months, detaches, and becomes free-floating mats as a result of environmental conditions, eventually becoming stranded on recreational beaches. Cladophora provides protection and nutrients, which allow enteric bacteria such as Escherichia coli, enterococci, Shigella, Campylobacter, and Salmonella to persist and potentially regrow in the presence of the algae. As a result of wind and wave action, these microorganisms can detach and be released to surrounding waters and can influence water quality. Enteric bacterial pathogens have been detected in Cladophora mats; E. coli and enterococci may populate to become part of the naturalized microbiota in Cladophora; the high densities of these bacteria may affect water quality, resulting in unnecessary beach closures. The continued use of traditional fecal indicators at beaches with Cladophora presence is inadequate at accurately predicting the presence of fecal contamination. This paper offers a substantial review of available literature to improve the knowledge of Cladophora impacts on water quality, recreational water monitoring, fecal indicator bacteria and microorganisms, and public health and policy.

Does the Macroduct collection system reliably define sweat chloride concentration in subjects with intermediate results?

OBJECTIVES: The sweat test remains the current diagnostic gold standard for CF disease. Many CF testing centres have switched from the Gibson and Cooke to the Macroduct. Since the validity and sensitivity of Macroduct has not been tested in patients with intermediate sweat chloride concentrations, we compared both methods simultaneously including subjects expected to have intermediate results. DESIGN AND METHODS: We prospectively evaluated controls, obligate heterozygotes, patients with CF and with an uncertain diagnosis of CF (congenital absence of the vas deferens, pancreatitis and sinopulmonary disease). RESULTS: We assessed 82 subjects (3.7-60.1 years); 14 healthy controls, 7 obligate heterozygotes, 20 CF (15 pancreatic insufficient, 5 pancreatic sufficient), and 41 with unproven diagnosis. Mean test difference was close to 0 (95% CI+/-20 mmol/L) and test values were highly correlated (r=0.93, p < or =0.0001). Discrepancies between the two testing methods occurred in 22% of subjects. CONCLUSION: Sweat chloride measured by Macroduct highly correlates with Gibson and Cooke for concentrations in all ranges, including the intermediate range. This study reveals the limitations of sweat testing for excluding a diagnosis of CF since 38% of subjects had intermediate range results.

The use of copper and silver in carbon point-of-use filters for the suppression of Legionella throughput in domestic water systems.

AIMS: To evaluate throughput of seeded Legionella pneumophila bacteria in domestic point-of-use filters. METHODS AND RESULTS: The filters were challenged with tap water seeded with Leg. pneumophila. After multiple challenge events (4.25 x 10(11) CFU per filter), the levels of Legionella were lower in the effluent from the filter containing both copper and silver (mean 4.48 x 10(3) CFU ml(-1)) than in the effluent from the filter containing copper only (1.26 x 10(4) CFU ml(-1); P < 0.001). After a single challenge event of approx. 5 x 10(9) CFU L. pneumophila per filter, there was no significant difference between the levels of Legionella in the effluents from a carbon filter containing copper and a carbon filter with no metals (mean 6.87 x 10(2) and 6.89 x 10(2) CFU ml(-1), respectively; P = 0.985). CONCLUSIONS: Legionella was detected in filter effluent up to 6 weeks after being challenged, indicating that while filters may reduce the levels during an initial contamination event, the exposure is extended as the accumulated bacteria slough off over time. SIGNIFICANCE AND IMPACT OF THE STUDY: This study has provided an understanding of the response of Legionella to the use of silver and copper in domestic point-of-use carbon filters.

Detection of Helicobacter pylori in sewage and water using a new quantitative PCR method with SYBR green.

AIMS: To demonstrate the application of a new quantitative polymerase chain reaction (qPCR) technique for the determination of Helicobacter pylori concentrations in water, and to use this method to investigate the occurrence of the bacteria in sewage. The other aim was to study the survival capacity and detectability of the bacteria in artificially contaminated groundwater at different temperatures of 4 and 15 degrees C. METHODS AND RESULTS: The detection of H. pylori in water was aided by PCR using specific primers designed for the amplification of a fragment within the major vacuolating cytotoxin gene. Conventional culture was compared with conventional PCR and the new real-time (RT) qPCR approach for the quantification of the bacterium. Helicobacter pylori remained culturable for 120 h at 4 degrees C as opposed to only 24 h at 15 degrees C. RT qPCR demonstrated a 100-fold greater sensitivity for the detection of H. pylori DNA in comparison with conventional PCR. Scanning electron microscopic (SEM) observation showed that the normal spiral form changed to a coccoid form after 24 and 72 h at 15 and 4 degrees C, respectively. Helicobacter pylori was found at 2-28 cells ml(-1) in sewage, of the 23 sewage samples - 84% were positive for H. pylori species-specific vacuolating cyctotoxin gene (vacA) by RT qPCR, but were negative by conventional PCR. CONCLUSIONS: The RT qPCR assay provided a specific, sensitive and rapid method for the quantitative detection of H. pylori in sewage. This molecular method would be valuable in studying the prevalence of H. pylori as required by the United States Environmental Protection Agency Contaminant Candidate List, particularly in nondisinfected ground waters, in sewage as a source of contamination, and for addressing the possible presence of viable but nonculturable of H. pylori. SIGNIFICANCE AND IMPACT OF THE STUDY: The quantitative detection of H. pylori by rapid and less-expensive methods than the TaqMan Assay using SYBR green could be an important tool to monitor infection in community by measuring the concentrations in sewage and to meet the new regulatory and risk-based frameworks for water supplies.

Epidemiology of juvenile idiopathic arthritis in a multiethnic cohort: ethnicity as a risk factor.

OBJECTIVE: To study the influence of ethnicity on the risk of developing juvenile idiopathic arthritis (JIA) in a multiethnic community of patients with unrestricted access to health care. METHODS: A questionnaire on ethnicity was distributed to all patients with JIA being followed up at the Hospital for Sick Children in Toronto, Ontario, Canada. Of 1,082 patients, 859 (79.4%) responded to the questionnaire. To calculate the relative risk (RR) of developing JIA in this study cohort, the results were compared with data from the age-matched general population of the Toronto metropolitan area (TMA) as provided in the 2001 census from Statistics Canada. RESULTS: European descent was reported by 69.7% of the patients with JIA compared with a frequency of 54.7% in the TMA general population, whereas a statistically significantly lower than expected percentage of the patients with JIA reported having black, Asian, or Indian subcontinent origin. Children of European origin had a higher RR for developing any of the JIA subtypes except polyarticular rheumatoid factor (RF)-positive JIA, and were particularly more likely to develop the extended oligoarticular and psoriatic subtypes. A higher frequency of enthesitis-related JIA was observed among patients of Asian origin, while those of black origin or native North American origin were more likely to develop polyarticular RF-positive JIA. CONCLUSION: In this multiethnic cohort, European descent was associated with a significantly increased risk of developing JIA, and the distribution of JIA subtypes differed significantly across ethnic groups.

Water reclamation, reuse and public health.

The number of people who have limited access to high-quality water has increased, and while this is a growing global crisis, water issues, problems and solutions are often seen as localised. Water reuse and reclamation will play a significant role in achieving sustainability and public health protection in the future. The wastewater and reuse community should be responsible for monitoring sewage impacts and improvements as demonstrated through pathogen reduction with appropriate treatment. Viruses, Cryptosporidium and Giardia can all be reduced during treatment anywhere from 99% to 99.9999%, achieving drinking water quality, if so desired. Recommendations to achieve better access to scientific information for decision making include: 1) developing a global data base for biological contaminant loading from wastewater and 2) defining the public health protection via reuse and reclamation.

Prevalence, risk factors, and outcome of uveitis in juvenile idiopathic arthritis: a long-term followup study.

OBJECTIVE: To assess the prevalence, risk factors, and long-term outcome of uveitis in patients with juvenile idiopathic arthritis (JIA). METHODS: An inception cohort of all 1,081 patients diagnosed as having JIA at a single tertiary care center was established. A questionnaire and followup telephone calls were used to confirm the diagnosis of uveitis. Ophthalmologists' records of patients with uveitis were collected. Kaplan-Meier and Cox regression analyses were used to assess risk factors for developing uveitis and for complications of uveitis. RESULTS: After a mean followup time of 6.9 years, 142 of 1,081 patients (13.1%) had developed uveitis. Risk factors were young age at diagnosis, female sex, antinuclear antibody positivity, and the subtype of JIA. The relative contribution of these risk factors was different for the different subtypes of JIA. Until the end of the study, uveitis complications had developed in 53 of 142 patients with uveitis (37.3%; 4.9% of the total cohort). Only 16 of 175 involved eyes (9.1%) in 14 of 108 patients (13%; 1.3% of the total cohort) for whom ophthalmology reports were available had best corrected visual acuity less than 20/40 (mean followup time for uveitis of 6.3 years). Abnormal vision was associated with synechiae or cataract. CONCLUSION: Risk factors for developing uveitis were different among subtypes of JIA. The long-term outcome of JIA-associated uveitis in our cohort was excellent despite the high rate of complications.

Tumour necrosis factor alpha inhibitors in the treatment of childhood uveitis.

OBJECTIVE: To describe the efficacy of anti-TNF-alpha agents in the treatment of childhood uveitis. METHODS: We performed a retrospective chart review of all children with uveitis treated with TNF-alpha blockers at The Hospital for Sick Children, Toronto. RESULTS: Twenty-one children with uveitis were treated with the anti-TNF-alpha agents etanercept (11 patients) and infliximab (13 patients), resulting in 24 treatment courses. All patients had persistently active uveitis despite treatment with at least one standard immunosuppressive drug before the start of anti-TNF-alpha therapy. Six of 21 patients (29%) had idiopathic uveitis. In the other 15 patients, the underlying disease was juvenile idiopathic arthritis in 12 (57%), Behçet disease in two (9%) and sarcoidosis in one (5%). Response to etanercept treatment was good in 27%, moderate in 27% and poor in 45% of patients. Response to infliximab treatment was good in 38%, moderate in 54% and poor in 8% of patients. The difference in the percentage of patients with a moderate or good response was statistically significant (P = 0.0481). We also observed a lower rate of complications, such as new-onset or worsening glaucoma or cataract in the infliximab-treated group. CONCLUSION: Anti-TNF-alpha treatment was beneficial in a high percentage of patients with childhood uveitis refractory to standard immunosuppressive treatment. Infliximab resulted in better clinical responses with less ocular complications than etanercept.

Microbiological assessment of ambient waters and proposed water sources for restoration of a Florida wetland.

This study evaluated the microbial quality of reclaimed and storm water as proposed sources for restoration of a Florida wetland. Bacterial indicators, bacteriophages and waterborne pathogenic microorganisms (Cryptosporidium, Giardia and infectious enteric viruses) were analysed during a 1-year period in order to determine potential public health risks associated with exposure to the proposed water sources for restoration. Ambient waters within the wetland (four active water wells and four major lakes) were included in the study in order to determine the microbial water quality before restoration. Storm water and lakes had the highest level of microbial contamination. Much lower levels of microbial indicators and waterborne pathogens were found in reclaimed water and groundwater. Pathogen occurrence in groundwater was intermittent. Owing to the small percentage of source waters (3.3%) migrating to the water wells, ambient concentration of microbial constituents in surface and groundwater could dominate microbial risk. The results of this study indicate that, in the light of the uncertainties involved in computing average Cryptosporidium concentrations, additional characterization of the current ambient water quality should be ongoing prior to restoration.

The influence of rainfall on the incidence of microbial faecal indicators and the dominant sources of faecal pollution in a Florida river.

AIMS: An assessment of microbial densities in an urbanized Florida watershed was performed during a period of changing rainfall patterns to investigate the role of climate coupled with urbanization in declining water quality. METHODS AND RESULTS: Concentrations of traditional and alternative faecal indicators were assessed by standard methods over 24 months. Sources of faecal contamination were determined by antibiotic resistance analysis (ARA) of faecal coliform (FC) bacteria. Composite indices of indicator organisms based on a suite of microbial measurements were used to quantify pollution impacts in the river. ARA results found that FC from wild animal sources dominated during the drought, and the relative frequency of FC from human sources increased after cumulative rainfall increased to near-normal levels. CONCLUSIONS: Changes observed in faecal indicator densities and in FC sources during changing rainfall patterns strongly suggest a role of precipitation on the sources and extent of microbial pollution in urbanized coastal watersheds. SIGNIFICANCE AND IMPACT OF THE STUDY: Bacterial source tracking coupled with a composite index of microbial contamination resulted in a more complete picture of microbial pollution within the river, as opposed to the general practice of reliance on one indicator organism. Improved land use decisions in urban areas are necessary to insure maintenance of coastal environmental health under changing climate patterns and population density.

Assessment of virulence-factor activity relationships (VFARs) for waterborne diseases.

Virulence-factor activity relationship (VFAR) is a concept that was developed as a way to relate the architectural and biochemical components of a microorganism to its potential to cause human disease. Development of these relationships requires specialised bioinformatics databases that do not exist at present. A pilot-scale VFAR database was designed for three different waterborne organisms: Escherichia coli, Norovirus and Cryptosporidium, to evaluate VFAR relationships. For the web-based database, each organism has separate pages containing virulence genes, occurrence genes, primer sets and probes, taxonomy, outbreaks, and serotype/species/genogroup/genotype. As the database continues to grow, it will be possible to relate the occurrence and prevalence of certain genes in various microorganisms to outbreak data and, subsequently, to establish the utility of using a combination of specific genes as markers of virulence and in establishing virulence-factor activity relationships (VFARs). The database and the VFARs established will be of use to the regulatory community as a way to assist with prioritising those organisms, which need to be regulated.

Rofecoxib administration to paediatric patients undergoing adenotonsillectomy.

BACKGROUND: Rofecoxib is a selective COX-2 inhibitor that does not interfere with platelet function and is associated with fewer bleeding complications than other nonsteroidal anti-inflammatory agents (NSAIDs). Our aims were to evaluate the safety and the efficacy of rofecoxib administration to paediatric patients undergoing adenotonsillectomy (T&A). METHODS: We conducted a double-blind, randomized, placebo-controlled study of rofecoxib in 45 ASA 1-2 patients > or = 4 years of age undergoing outpatient T&A. All patients received midazolam 0.5 mg x kg(-1) (max 15 mg) p.o. and either rofecoxib 1 mg x .kg(-1) (max 25 mg) or placebo p.o. 30 min preoperatively. All patients had a standardized anaesthetic and were extubated awake in the operating room at the conclusion of surgery. The Children's Hospital of Eastern Ontario Pain Scale (CHEOPS) scores were obtained on arrival in the postanaesthetic care unit (PACU). Morphine 25 microg x kg(-1) i.v. were administered up to six times for pain in the PACU. Wong-Baker FACES Scales were obtained at discharge from the PACU and the day surgery unit (DSU). Outcome measures included intraoperative estimated blood loss (EBL), pain scores, PACU morphine requirements and discharge times. RESULTS: There were 23 patients in the rofecoxib group and 22 patients in the placebo group. There were no differences between the rofecoxib and placebo groups in terms of bleeding, pain scores, PACU morphine requirements, PACU times or DSU times. CONCLUSION: Rofecoxib administration to paediatric patients undergoing T&A did not result in increased bleeding. Rofecoxib, however, was not found to decrease morphine use or improve pain scores prior to hospital discharge in T&A patients who received intraoperative morphine and acetaminophen.