Spatial constraints and cell surface molecule depletion structure a randomly connected learning circuit.

The brain can represent almost limitless objects to "categorize an unlabeled world" (Edelman, 1989). This feat is supported by expansion layer circuit architectures, in which neurons carrying information about discrete sensory channels make combinatorial connections onto much larger postsynaptic populations. Combinatorial connections in expansion layers are modeled as randomized sets. The extent to which randomized wiring exists in vivo is debated, and how combinatorial connectivity patterns are generated during development is not understood. Non-deterministic wiring algorithms could program such connectivity using minimal genomic information. Here, we investigate anatomic and transcriptional patterns and perturb partner availability to ask how Kenyon cells, the expansion layer neurons of the insect mushroom body, obtain combinatorial input from olfactory projection neurons. Olfactory projection neurons form their presynaptic outputs in an orderly, predictable, and biased fashion. We find that Kenyon cells accept spatially co-located but molecularly heterogeneous inputs from this orderly map, and ask how Kenyon cell surface molecule expression impacts partner choice. Cell surface immunoglobulins are broadly depleted in Kenyon cells, and we propose that this allows them to form connections with molecularly heterogeneous partners. This model can explain how developmentally identical neurons acquire diverse wiring identities.

COVID-19 vaccination hesitance and adverse effects among US adults: a longitudinal cohort study.

Introduction: Although Coronavirus disease 2019 (COVID-19) vaccination is critical to control its spread, vaccine hesitancy varies significantly among the United States population; moreover, some vaccine recipients experienced various adverse effects. We aim to assess the impact of COVID-19 vaccine hesitancy in a university-affiliated community, the factors affecting participants' decisions, and their adverse effects. Methods: A pre-vaccination online Institutional Review Board IRB-approved survey was emailed in Nov/Dec 2020, 2 months before the implementation of state-policy protocols for COVID-19 vaccination. A post-vaccination survey was emailed in May/June 2021, two months after protocol execution. A third follow-up survey was sent in Nov/Dec 2021, and a fourth was sent in June/July 2022. The study population included three groups of adult participants: university students, faculty, and staff-(MS), university health system patients-(MP), and Cancer Center patients-(MCP). The study was designed as a longitudinal cohort study. Statistical analyses were performed using SPSS. Results: With a combined response rate of 26% (40,578/157,292) among the four surveys, 15,361 participants completed the first survey (MS = 4,983, MP = 9,551, and MCP = 827). 2/3 of participants (63.5%) were willing to get vaccinated, with a significant difference in acceptance among groups, MS:56.6%, MP:66.2%, and MCP:71.6% (p < 0.05). Vaccine acceptance rates reached 89% in the second survey after the vaccine's approval, with a lower acceptance rate of MS:84.6% than with MP:90.74% and MCP:92.47% participants (p < 0.05). Safety and effectiveness concerns were the main factors affecting participants' decisions in all the first three surveys; however, participants reported these concerns decreased between pre-vaccination, post-vaccination, and follow-up surveys with 87%, 56%, and 46%, respectively(p < 0.05). More than two-thirds of the participants (70%) reported having either minor/moderate symptoms (61.6%) or major symptoms (8.6%) after getting some of the vaccine doses (p < 0.05). Conclusion: The hesitance of COVID-19 vaccination was associated with concerns regarding its safety and efficacy. Vaccine acceptance rose higher than expected after protocol execution, likely due to continuous education, whereas safety and efficacy remain factors hindering vaccine acceptance. Continuous education focusing on safety and efficacy of the vaccine can reduce vaccine hesitancy and raise the rates of vaccination.

Let's talk about sex: Mechanisms of neural sexual differentiation in Bilateria.

In multicellular organisms, sexed gonads have evolved that facilitate release of sperm versus eggs, and bilaterian animals purposefully combine their gametes via mating behaviors. Distinct neural circuits have evolved that control these physically different mating events for animals producing eggs from ovaries versus sperm from testis. In this review, we will describe the developmental mechanisms that sexually differentiate neural circuits across three major clades of bilaterian animals-Ecdysozoa, Deuterosomia, and Lophotrochozoa. While many of the mechanisms inducing somatic and neuronal sex differentiation across these diverse organisms are clade-specific rather than evolutionarily conserved, we develop a common framework for considering the developmental logic of these events and the types of neuronal differences that produce sex-differentiated behaviors. This article is categorized under: Congenital Diseases > Stem Cells and Development Neurological Diseases > Stem Cells and Development.

The Protein Interactome of Streptococcus pneumoniae and Bacterial Meta-interactomes Improve Function Predictions.

The functions of roughly a third of all proteins in Streptococcus pneumoniae, a significant human-pathogenic bacterium, are unknown. Using a yeast two-hybrid approach, we have determined more than 2,000 novel protein interactions in this organism. We augmented this network with meta-interactome data that we defined as the pool of all interactions between evolutionarily conserved proteins in other bacteria. We found that such interactions significantly improved our ability to predict a protein's function, allowing us to provide functional predictions for 299 S. pneumoniae proteins with previously unknown functions. IMPORTANCE Identification of protein interactions in bacterial species can help define the individual roles that proteins play in cellular pathways and pathogenesis. Very few protein interactions have been identified for the important human pathogen S. pneumoniae. We used an experimental approach to identify over 2,000 new protein interactions for S. pneumoniae, the most extensive interactome data for this bacterium to date. To predict protein function, we used our interactome data augmented with interactions from other closely related bacteria. The combination of the experimental data and meta-interactome data significantly improved the prediction results, allowing us to assign possible functions to a large number of poorly characterized proteins.

A cross-sectional study examining Campylobacter and other zoonotic enteric pathogens in dogs that frequent dog parks in three cities in south-western Ontario and risk factors for shedding of Campylobacter spp.

An estimated 6 million pet dogs live in Canadian households with the potential to transmit zoonotic pathogens to humans. Dogs have been identified as carriers of Salmonella, Giardia and Campylobacter spp., particularly Campylobacter upsaliensis, but little is known about the prevalence and risk factors for these pathogens in pet dogs that visit dog parks. This study examined the prevalence of these organisms in the faeces of dogs visiting dog parks in three cities in south-western Ontario, as well as risk factors for shedding Campylobacter spp. and C. upsaliensis. From May to August 2009, canine faecal samples were collected at ten dog parks in the cities of Guelph and Kitchener-Waterloo, Ontario, Canada. Owners were asked to complete a questionnaire related to pet characteristics and management factors including age, diet and activities in which the dog participates. Faecal samples were collected from 251 dogs, and 189 questionnaires were completed. Salmonella, Giardia and Campylobacter spp. were present in 1.2%, 6.4% and 43.0% of faecal samples, respectively. Of the Campylobacter spp. detected, 86.1% were C. upsaliensis, 13% were C. jejuni and 0.9% were C. coli. Statistically significant sparing factors associated with the shedding of Campylobacter spp. included the feeding of a commercial dry diet and the dog's exposure to compost. Age of dog had a quadratic effect, with young dogs and senior dogs having an increased probability of shedding Campylobacter spp. compared with adult dogs. The only statistically significant risk factor for shedding C. upsaliensis was outdoor water access including lakes and ditches, while dogs >1 year old were at a lower risk than young dogs. Understanding the pet-related risk factors for Campylobacter spp. and C. upsaliensis shedding in dogs may help in the development of awareness and management strategies to potentially reduce the risk of transmitting this pathogen from dogs to humans.

A cross-sectional study examining the prevalence and risk factors for anti-microbial-resistant generic Escherichia coli in domestic dogs that frequent dog parks in three cities in south-western Ontario, Canada.

Anti-microbial resistance can threaten health by limiting treatment options and increasing the risk of hospitalization and severity of infection. Companion animals can shed anti-microbial-resistant bacteria that may result in the exposure of other dogs and humans to anti-microbial-resistant genes. The prevalence of anti-microbial-resistant generic Escherichia coli in the faeces of dogs that visited dog parks in south-western Ontario was examined and risk factors for shedding anti-microbial-resistant generic E. coli identified. From May to August 2009, canine faecal samples were collected at ten dog parks in three cities in south-western Ontario, Canada. Owners completed a questionnaire related to pet characteristics and management factors including recent treatment with antibiotics. Faecal samples were collected from 251 dogs, and 189 surveys were completed. Generic E. coli was isolated from 237 of the faecal samples, and up to three isolates per sample were tested for anti-microbial susceptibility. Eighty-nine percent of isolates were pan-susceptible; 82.3% of dogs shed isolates that were pan-susceptible. Multiclass resistance was detected in 7.2% of the isolates from 10.1% of the dogs. Based on multilevel multivariable logistic regression, a risk factor for the shedding of generic E. coli resistant to ampicillin was attending dog day care. Risk factors for the shedding of E. coli resistant to at least one anti-microbial included attending dog day care and being a large mixed breed dog, whereas consumption of commercial dry and home cooked diets was protective factor. In a multilevel multivariable model for the shedding of multiclass-resistant E. coli, exposure to compost and being a large mixed breed dog were risk factors, while consumption of a commercial dry diet was a sparing factor. Pet dogs are a potential reservoir of anti-microbial-resistant generic E. coli; some dog characteristics and management factors are associated with the prevalence of anti-microbial-resistant generic E. coli in dogs.

International outbreak investigation of Salmonella Heidelberg associated with in-flight catering.

Rapid and wide dispersal of passengers after flights makes investigation of flight-related outbreaks challenging. An outbreak of Salmonella Heidelberg was identified in a group of Irish travellers returning from Tanzania. Additional international cases sharing the same flight were identified. Our aim was to determine the source and potential vehicles of infection. Case-finding utilized information exchange using experts' communication networks and national surveillance systems. Demographic, clinical and food history information was collected. Twenty-five additional cases were identified from Ireland, The Netherlands, Norway, USA and Canada. We conducted a case-control study which indicated a significant association between illness and consumption of milk tart (OR 10.2) and an egg dish (OR 6) served on-board the flight. No food consumed before the flight was associated with illness. Cases from countries other than Ireland provided supplementary information that facilitated the identification of likely vehicles of infection. Timely, committed international collaboration is vital in such investigations.

Antibiotic recommendations of office-based physicians, 2007-2011.

OBJECTIVE: To describe patterns of antibiotic recommendations by office-based physicians from five regions in Canada between 2007 and 2011. METHODS: Values were estimated based on quarterly data from a sample of approximately 652 physicians stratified by region and specialty. For four consecutive quarters, each physician maintained a practice diary describing information on every patient visit during a randomly selected 48-hour period. This information was then extrapolated using a projection factor to estimate prescriptions by all physicians across Canada. RESULTS: Over the five-year surveillance period, physicians saw patients for almost 1.5 billion diagnoses with approximately 120 million antimicrobial recommendations. In 2011 alone, 289 million clinical diagnoses were made of which 8% resulted in an antimicrobial being recommended. The majority of these (51%) were for the treatment of diseases of the respiratory system, 14% for infections of the urinary tract, and 11% for diseases of skin and subcutaneous tissue. Antimicrobial recommendations were highest for patients in the age groups of 0-2, 3-9, and 65 or older. Antimicrobial recommendation rates generally decreased between 2007 and 2011 except for diseases of the genitourinary system and diseases of the ear that remained stable. Overall, the most commonly recommended antimicrobials included macrolides, penicillins with extended spectrum, and fluoroquinolones. Although not as common, there was a 42% increase in the number of physician recommendations for third generation cephalosporins. CONCLUSION: With the exception of third generation cephalosporins, the percentage of antimicrobial recommendations by office-based physicians in Canada remained stable or decreased between 2007 and 2011. Provincial differences were observed in the antimicrobial recommendations and rates, with the Atlantic region and Québec having higher rates of antimicrobial recommendations compared to the overall national level.

Antibiotic purchasing by Canadian hospitals, 2007-2011.

OBJECTIVE: To describe patterns of antibiotic purchasing by Canadian hospitals from five regions in Canada between 2007 and 2011. METHODS: The Canadian Drugstore and Hospital Purchases Audit (CDH) dataset measures the dollar value and unit volume of pharmaceutical products from over 700 hospitals and is extrapolated to represent purchases by more than 800 hospitals in Canada. General population information was used for developing the rates of purchasing with a primary focus on unit volume. RESULTS: In 2011, there was a 7% increase in total antibiotics purchased by Canadian hospitals compared to 2010, with slight increases in the purchasing levels for oral (8% increase) and parenteral (3% increase) antibiotics. Antibiotics considered of very high importance to human medicine (Category I) continued to represent a high proportion of the total antibiotics used in hospitals in 2011. Overall, consumption of antibiotics was highest in Manitoba at 2.61 doses per 1,000 inhabitants per day (DID), while Ontario had the lowest levels of consumption (1.26 DID). New Brunswick had the highest proportion of Category I consumption (43%, 0.62/1.43 DID) for 2011, driven by higher levels of fluoroquinolones consumed in that province. CONCLUSION: Canadian hospitals have purchased an increasing number of antibiotics and are consuming slightly more oral and parenteral antibiotics. Overall, consumption was highest in Manitoba and total cost was highest in British Columbia. Ontario had the lowest level of consumption of anitbiotics and the lowest overall cost.

Canadian integrated program for antimicrobial resistance surveillance: Retail food highlights, 2003-2012.

BACKGROUND: The Canadian Integrated Program for Antimicrobial Resistance Surveillance (CIPARS) is a collaborative, integrated program designed to track antimicrobial resistance (AMR) among enteric bacteria isolated from various livestock commodities along the food-producing continuum ("farm to fork") and in humans. OBJECTIVE: To provide a summary of the prevalence and trends in AMR among select bacteria isolated from raw, fresh chicken, pork, and beef in 2012 at the retail food level and to link these data with other findings from CIPARS. METHODS: Meat samples were collected from randomly selected geographic areas across Canada weighted by population for subsequent isolation of bacteria and interpretation of the associated AMR profiles. Salmonella, Campylobacter and generic Escherichia coli (E. coli) were tested in chicken, and E. coli was tested in beef and pork. Data were analyzed for 2012 and temporal and regional trends were examined between 2003 and 2012 by province/region. RESULTS: Overall, resistance levels to Salmonella in retail chicken varied widely by region and year. For example, ceftiofur resistance to Salmonella in retail chicken was significantly lower in 2012 than in 2004 in Ontario and in Québec; however, among all regions sampled, resistance was significantly higher in 2012 compared to 2006. Across all regions sampled, resistance to Campylobacter in retail chicken was relatively low in 2012 (<16%) with the exception of tetracycline resistance. In 2012, ciprofloxacin resistance to Campylobacter in chicken declined in British Columbia but significantly increased in Ontario, compared to 2011. In 2012, ß-lactam resistance to E. coli in retail beef remained low (≤1%) and was also relatively low comparable to previous years in pork. CONCLUSION: In Canada, as is the case worldwide, there is evidence of resistance to medically important antimicrobials among bacteria from retail meats. Resistance among organisms isolated from poultry, beef, and pork at the retail food level is characterized by wide variation over time and across different regions.

New resources to address antibiotic resistance are just a click away.

Antibiotic resistance is a complex issue with multiple causes, and there are many roles to play in addressing it. As part of its response, the Public Health Agency of Canada is launching a pilot antibiotic awareness campaign for Canadian families and health care professionals. Coinciding with Antibiotic Awareness Week, starting on November 17, 2014, the goal of this campaign is to improve knowledge and awareness of antibiotic resistance in Canada. To achieve this, the Agency has developed a suite of resources for both Canadian families and health care providers featuring a variety of key messages explaining antibiotic resistance, why it is important, and how to reduce the risks associated with it. Resources for Canadian families include an online informational video, an educational brochure, and infographics for both adults and children. Resources for health care professionals include two online Continuing Medical Education Modules, a letter that physicians can sign and provide to parents explaining why an antibiotic was not prescribed, and two webinars to present trends in antimicrobial resistance (AMR) and antimicrobial use. Health professionals will also receive an electronic postcard and a bilingual campaign poster. Promoting the campaign messages and using these campaign resources will support health professionals in discussions about antibiotic resistance with their patients or clients, and in their continuing efforts to be part of the solution in addressing this important global health challenge.

Integrated surveillance and potential sources of Salmonella enteritidis in human cases in Canada from 2003 to 2009.

Salmonella enteritidis has emerged as the most prevalent cause of human salmonellosis in Canada. Recent trends of S. enteritidis subtypes and their potential sources were described by integrating Salmonella data from several Canadian surveillance and monitoring programmes. A threefold increase in S. enteritidis cases from 2003 to 2009 was identified to be primarily associated with phage types 13, 8 and 13a. Other common phage types (4, 1, 6a) showed winter seasonality and were more likely to be associated with cases linked to international travel. Conversely, phage types 13, 8 and 13a had summer seasonal peaks and were associated with cases of domestically acquired infections. During agri-food surveillance, S. enteritidis was detected in various commodities, most frequently in chicken (with PT13, PT8 and PT13a predominating). Antimicrobial resistance was low in human and non-human isolates. Continued integrated surveillance and collaborative prevention and control efforts are required to mitigate future illness.

Factors related to Campylobacter spp. carriage in client-owned dogs visiting veterinary clinics in a region of Ontario, Canada.

From July 2008 until May 2009, 240 client-owned pet dogs from seven veterinary clinics in the Region of Waterloo, Ontario, Canada participated in a study to determine pet-related management factors that may be associated with the presence of Campylobacter spp. in dogs. The prevalence of Campylobacter spp. carriage in our study population of pet dogs was 22%, with 19% of the dogs positive for C. upsaliensis, and 3% positive for C. jejuni. A significant risk factor from multivariable logistic regression models for both Campylobacter spp. and C. upsaliensis carriage was having homemade cooked food as the dog's diet or added to its diet, and a significant sparing factor for both models was treatment with antibiotics in the previous month. Increasing age of the dog decreased the odds of Campylobacter spp. and C. upsaliensis carriage. Based on the high prevalence of Campylobacter, and specifically C. upsaliensis, further research concerning pet dogs as a risk factor for campylobacteriosis in humans is warranted.

Evaluation of pet-related management factors and the risk of Salmonella spp. carriage in pet dogs from volunteer households in Ontario (2005-2006).

The purpose of this study was to determine pet-related management factors that may be associated with the presence of Salmonella spp. in feces of pet dogs from volunteer households. From October 2005 until May 2006, 138 dogs from 84 households in Ontario were recruited to participate in a cross-sectional study. Five consecutive daily fecal samples were collected from each dog and enrichment culture for Salmonella spp. was performed. A higher than expected number of the dogs (23.2%; 32/138) had at least one fecal sample positive for Salmonella, and 25% (21/84) of the households had at least one dog shedding Salmonella. Twelve serotypes of Salmonella enterica subsp. enterica were identified, with the predominant serotypes being Typhimurium (33.3%; 13/39), Kentucky (15.4%; 6/39), Brandenburg (15.4%; 6/39) and Heidelberg (12.8%; 5/39). Univariable logistic regression models were created with a random effect for household to account for clustering. Statistically significant risk factors for a dog testing positive included having contact with livestock, receiving a probiotic in the previous 30 days, feeding a commercial or homemade raw food diet, feeding raw meat and eggs, feeding a homemade cooked diet, and having more than one dog in the household. In two-variable models that controlled for feeding raw food, the non-dietary variables were no longer statistically significant. These results highlight the potential public health risk of including raw animal products in canine diets.

Characterization of antimicrobial resistance, molecular and phage types of Salmonella enterica serovar Typhi isolations.

Isolation rates in Canada of Salmonella enterica serovar Typhi increased from 0.29 to 0.55 isolations/100,000 population during 2000-2006. Although no ciprofloxacin resistance was detected, nalidixic acid resistance increased from 41% to 80%. Multidrug-resistant S. Typhi represented 18% of the strains tested. Pulsed-field gel electrophoresis (PFGE) analysis of 222 isolates resulted in 91 distinct patterns clustering into four major genetic similarity groups. The five most frequently occurring PFGE patterns accounted for 46% of the isolates. Drug-resistant isolates predominantly occurred in one PFGE similarity group. There were 39 phage types identified in 826 isolates analysed with 60% described by five phage types; 134 were untypable. The phage types associated with multidrug resistance were phage types 53, B1, D1, E1, E9, G3 and M1. Improved integration of epidemiological and laboratory case data will facilitate the protection of public health in Canada during an era of increasing travel and globalization.

Evaluation of Clostridium difficile in dogs and the household environment.

Clostridium difficile may be an emerging community-associated pathogen but little is known about its sources of exposure. This study evaluated C. difficile contamination in households and colonization of pets. C. difficile was isolated from 44/836 (5.3%) sites in 26/84 (31%) households. Ribotype 027 was the most common (25%) environmental strain. C. difficile was isolated from 14/139 (10%) dogs. Living with an immunocompromised individual was associated with C. difficile colonization in dogs. All toxigenic strains identified in pets have been isolated from humans in Ontario. C. difficile was isolated concurrently from dogs and the environment in four households, but in all cases canine and environmental ribotypes were different. C. difficile was relatively common in households, suggesting that exposure to this pathogen may be a regular event. There was no evidence that dogs are a significant source of household C. difficile contamination.

The occurrence and antimicrobial susceptibility of salmonellae isolated from commercially available canine raw food diets in three Canadian cities.

The purpose of the present study was to evaluate the prevalence and antimicrobial resistance patterns of Salmonella isolated from commercially available canine raw food diets in Canada. A total of 166 commercial frozen raw food diet samples were purchased from randomly selected local pet stores in three Canadian cities for a period of 8 months. All samples were evaluated for the presence of Salmonella, serotyped and tested for antimicrobial susceptibility. There was an overall Salmonella prevalence of 21%; chicken was an ingredient for 67% of the Salmonella-positive diets. Eighteen different Salmonella serotypes were recovered, and resistance was observed to 12 of the 16 antimicrobials tested, with the majority of Ontario isolates exhibiting resistance to ampicillin and Calgary isolates to tetracycline. This study demonstrates the potential risk of raw food diets, especially for immunocompromised individuals, and stresses the need for implementing regulatory guidelines for the production of these diets in order to help control and ideally eliminate the bacterial risks associated with their use and consumption.

The occurrence and anti-microbial susceptibility of Salmonellae isolated from commercially available pig ear pet treats.

In Canada, there have been reported outbreaks of human salmonellosis related to exposure to animal-derived pet treats, involving pig ear treats, beef steak patty dog treats and pet treats of seafood origin. As a follow-up to recommendations made to the pig ear treat industry in 1999, a total of 245 pig ear treats were purchased in two Canadian cities to provide evidence of adoption of the recommendations and to determine the current levels of Salmonella contamination of pig ear treats available at pet stores. An overall prevalence of 4% was observed, with isolates exhibiting resistance to up to seven anti-microbials. Serotypes recovered included S. Bovismorbificans, S. Give, S. Derby and S. Typhimurium var. Copenhagen. Although the prevalence observed during this study is lower than the prevalence observed in 1999, pig ear treats should still be considered as a possible source of Salmonella and anti-microbial resistant bacteria to humans and dogs in Canada.

A change in clinical practice: a partially stapled cervical esophagogastric anastomosis reduces morbidity and improves functional outcome after esophagectomy for cancer.

Cervical esophagogastric anastomoses are commonly used for reconstruction after esophagectomy because of the lower mortality rate associated with an anastomotic leak compared to intrathoracic anastomoses. However, cervical esophagogastric anastomoses have been criticized for their higher leak rates, stricture formation and greater need for later dilatations when compared with intrathoracic anastomoses. Multiple studies have looked at varying techniques to improve the outcome of the cervical esophagogastric anastomosis. This study was performed to determine whether a partially stapled (posterior stapled wall and anterior hand-sewn wall) anastomosis reliably reduced leaks and the need for later dilatation. From January 2001 to March 2006, 168 patients who underwent cervical esophagogastric anastomosis following esophagectomy (transhiatal or three-hole) for cancer were identified. Beginning in September 2003, the partially stapled technique was introduced and used in 79 patients. Clinical outcomes were compared to patients in whom hand-sewn technique was used (n = 89). Outcomes related to anastomotic leak, other hospital complications, length of stay, postoperative dilatations and survival were compared using Student's t-tests and chi-square tests (P < 0.05), as well as multiple regression analyses. An anastomotic leak occurred in 10 (12.7%) patients who received a partially stapled anastomosis. A hand-sewn anastomosis was complicated by an anastomotic leak in 24 patients (27.0%). This difference was statistically significant (P = 0.021). This lowered incidence of leak was associated with an earlier initiation of oral feeds (median 7 vs. 9.5 days, P < 0.001) and a reduction in hospital stay (median 10 vs. 15 days, P < 0.001). Furthermore, dysphagia associated with stricture requiring postoperative dilatations was markedly diminished in the stapled anastomosis [23 (31.3%) vs. 49 (55.1%), P = 0.001]. The partially stapled cervical esophagogastric anastomosis significantly decreased the incidence of postoperative anastomotic leaks and the need for postoperative dilatation to treat strictures compared to the hand-sewn anastomosis.

Development and validation of a disease-specific quality of life questionnaire (EQOL) for potentially curable patients with carcinoma of the esophagus.

The objective was to develop, pretest and validate a disease-specific quality of life questionnaire for potentially curable patients with esophageal carcinoma, for use with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) in order to assess the quality of life associated with the various treatment modalities available for this disease. Questionnaire development phase Patients were enrolled in three centres. Literature reviews, patients, family members, and health care professionals generated 195 items: symptoms (55); emotions (53); physical functioning (17); activities of daily living (ADL) (48); and leisure/social (22). Thirty-eight patients identified items of importance and assigned importance ratings on a 5-point Likert scale. Impact scores were calculated as frequency times mean item importance. Item impact scores<20/100 were excluded. Pearson's correlation co-efficients compared domains with the Medical Outcomes Study SF-20 (MOS SF-20). Fifteen items remained. Questionnaire validation phase EORTC QLQ-C30, Esophageal Quality of Life Questionnaire (EQOL), MOS SF-36 and a Global Rating of Change Questionnaire were completed at baseline, 1 week after baseline but prior to any treatment, 1 month, 3 months, and 6 months after treatment began. Reliability was assessed using paired samples correlations. Responsiveness was assessed between mean scores of changed and unchanged patients, and a responsiveness index was calculated. The MOS SF-36 was used for criterion validity. Construct validity included four a priori predictions. Sixty-five patients were enrolled in four centres in the validation phase. Paired samples correlations were high for all domains (0.749-0.889) indicating good reliability. Symptom, physical function and social domains were responsive to change at all time intervals (P<0.05). Emotional function was responsive at 1 and 3 months, activities of daily living (ADLs) at 1 and 6 months. Magnitude of change was significant when direction of change was stated. Between better and worse, magnitude of change was significant in all domains except at 6 months in symptoms, emotional and physical domains. The minimal clinically important difference was consistently around 0.5 for all domains. Minimal, moderate and large effect ranges were established. Only 2/16 time intervals had poor correlations with the SF-36, establishing criterion validity. Of the four a priori predictions for construct validity, only the second part of one prediction, in the emotional function domain, was not confirmed. We have developed a 15-item questionnaire (EQOL) which has good reliability, responsiveness and validity and is now in use in studies in Canadian centres with the EORTC QLQ-C30.