An international multidisciplinary consensus statement on fasting before procedural sedation in adults and children.

The multidisciplinary International Committee for the Advancement of Procedural Sedation presents the first fasting and aspiration prevention recommendations specific to procedural sedation, based on an extensive review of the literature. These were developed using Delphi methodology and assessment of the robustness of the available evidence. The literature evidence is clear that fasting, as currently practiced, often substantially exceeds recommended time thresholds and has known adverse consequences, for example, irritability, dehydration and hypoglycaemia. Fasting does not guarantee an empty stomach, and there is no observed association between aspiration and compliance with common fasting guidelines. The probability of clinically important aspiration during procedural sedation is negligible. In the post-1984 literature there are no published reports of aspiration-associated mortality in children, no reports of death in healthy adults (ASA physical status 1 or 2) and just nine reported deaths in adults of ASA physical status 3 or above. Current concerns about aspiration are out of proportion to the actual risk. Given the lower observed frequency of aspiration and mortality than during general anaesthesia, and the theoretical basis for assuming a lesser risk, fasting strategies in procedural sedation can reasonably be less restrictive. We present a consensus-derived algorithm in which each patient is first risk-stratified during their pre-sedation assessment, using evidence-based factors relating to patient characteristics, comorbidities, the nature of the procedure and the nature of the anticipated sedation technique. Graded fasting precautions for liquids and solids are then recommended for elective procedures based upon this categorisation of negligible, mild or moderate aspiration risk. This consensus statement can serve as a resource to practitioners and policymakers who perform and oversee procedural sedation in patients of all ages, worldwide.

Prevalence of negative behaviour in the dental setting and association with sociodemographic, oral health-related and psychosocial factors amongst Brazilian preschool children.

PURPOSE: To investigate the prevalence of negative behaviour in preschool children attending dental clinics and its association with sociodemographic, oral health-related and parental psychosocial factors. METHODS: A cross-sectional study was carried out with 145 parents/guardians and their children aged 4-6 years attending paediatric dentistry training programmes in a capital city of Midwest Brazil. Data were obtained from children's dental records, interviews, and questionnaires for parents/guardians. The outcome was negative child behaviour, based on the dentists' use or indication of behavioural control measures during the dental appointments, as registered in the children's dental records. Covariates were sociodemographic, clinical and parent/guardian psychosocial factors religiosity (DUREL index) and Sense of Coherence (SOC-13 scale). Bivariate analyses and Poisson regression with robust variance were performed. RESULTS: The prevalence of negative behaviour was 24.1% (95% CI = 17.9-31.7). In the bivariate analyses, the variables initially selected for the regression models (p < 0.25) were the parent/guardians' number of children and religiosity, and the children's dental pain and caries status in deciduous teeth. After adjustment, the prevalence of negative behaviour was 2.12 higher in children with teeth extracted due to caries. CONCLUSION: The prevalence of negative behaviour was high and associated with the presence of missing teeth due to caries, regardless of sociodemographic, psychosocial, and other oral health factors.

Nociception associated with pain/distress in young children sedated for dental treatment: a clinical study with objective and subjective measures.

PURPOSE: To evaluate the association between children's pain/distress levels and patient characteristics (age, sex, history of dental pain), sedation type (level of sedation, sedative regimen), nociception and pain intensity reported by the parents in sedated children undergoing minimally invasive dental treatment. METHODS: This clinical study evaluated secondary outcomes of an RCT that evaluated the efficacy of dexmedetomidine sedation with or without ketamine. Only children who had nociception levels recorded using the Analgesia Nociception Index (ANI) were included (0-100; 0 = highest nociception). FLACC scale (Face, Legs, Activity, Cry and Consolability) was used to assess children's pain/distress (0-10; 0 = no pain/distress). Parental proxy report of the child's pain intensity during the treatment was performed using the Visual Analogue Scale (VAS; 0-100; 0 = no pain). The association between ANI, children's age and sex, dental pain history, sedation level, sedative regimen, and VAS with the FLACC was verified using the generalised estimation equation analysis (alpha 0.05). RESULTS: Participants were 31 children (51.6% boys) and their parents (90.3% mothers). Median FLACC was 3.3 (25th-75th percentiles 1.7-8.2), ANI 80.9 (74.7-85.8), and VAS 10 (1-23). FLACC associated with ANI (OR 0.96; 95% CI 0.93-0.99; p = 0.02), moderate sedation (0.13; 0.03-0.50; p = 0.003), and VAS (1.05; 1.01-1.10; p = 0.01). CONCLUSION: Pain/distress was generally low and more prominent with minimal (versus moderate) sedation and higher nociception.

Functional modelling of an equine bronchoalveolar lavage fluid proteome provides experimental confirmation and functional annotation of equine genome sequences.

The equine genome sequence enables the use of high-throughput genomic technologies in equine research, but accurate identification of expressed gene products and interpreting their biological relevance require additional structural and functional genome annotation. Here, we employ the equine genome sequence to identify predicted and known proteins using proteomics and model these proteins into biological pathways, identifying 582 proteins in normal cell-free equine bronchoalveolar lavage fluid (BALF). We improved structural and functional annotation by directly confirming the in vivo expression of 558 (96%) proteins, which were computationally predicted previously, and adding Gene Ontology (GO) annotations for 174 proteins, 108 of which lacked functional annotation. Bronchoalveolar lavage is commonly used to investigate equine respiratory disease, leading us to model the associated proteome and its biological functions. Modelling of protein functions using Ingenuity Pathway Analysis identified carbohydrate metabolism, cell-to-cell signalling, cellular function, inflammatory response, organ morphology, lipid metabolism and cellular movement as key biological processes in normal equine BALF. Comparative modelling of protein functions in normal cell-free bronchoalveolar lavage proteomes from horse, human, and mouse, performed by grouping GO terms sharing common ancestor terms, confirms conservation of functions across species. Ninety-one of 92 human GO categories and 105 of 109 mouse GO categories were conserved in the horse. Our approach confirms the utility of the equine genome sequence to characterize protein networks without antibodies or mRNA quantification, highlights the need for continued structural and functional annotation of the equine genome and provides a framework for equine researchers to aid in the annotation effort.

Paediatric dentists' stress during dental care for children under sedation: a cross-sectional study.

PURPOSE: The knowledge of the stress related to the practice of paediatric dentistry is scarce. The aim of this study was to verify the stress perceived by paediatric dentists related to young children's dental treatment under sedation and their association with child's behaviour and other independent variables. METHODS: A cross-sectional repeated measures study was performed with four paediatric dentists who treated 81 sedated preschoolers. Paediatric dentists reported their stress at the end of the session using the visual analog scale (VAS 0-100 mm). Samples of saliva were collected to measure the dentists' salivary cortisol level throughout the dental session. The sessions of dental treatment were video recorded for evaluation of the child's behaviour. Children's behaviour was assessed using the Ohio State University Behavioral Rating Scale (OSUBRS). The association between the VAS scores and the other variables was verified using bivariate tests and generalised estimating equation (alpha 0.05). RESULTS: Paediatric dentists felt slightly stressed in most of the sessions (VAS median 7 points; minimum 0, maximum 97 points). VAS associated with the struggling behaviour of the child (B 0.53; 95%CI 0.32-0.74; p ≤ 0.001) and the time since dentist's graduation (B - 1.41, 95% CI - 1.87 to - 0.94; p ≤ 0.001) but not with dentist's salivary cortisol (rho - 0.053, p = 0.639). CONCLUSION: The more frequent the child's struggling behaviour during dental treatment and the shorter the time elapsed since the professional's graduation, the higher the level of objectively and subjectively measured stress of the paediatric dentist during the dental procedure.

Biochemical characterization of adenosine deaminase (CD26; EC 3.5.4.4) activity in human lymphocyte-rich peripheral blood mononuclear cells.

The conversion of adenosine to inosine is catalyzed by adenosine deaminase (ADA) (EC 3.5.4.4), which has two isoforms in humans (ADA1 and ADA2) and belongs to the zinc-dependent hydrolase family. ADA modulates lymphocyte function and differentiation, and regulates inflammatory and immune responses. This study investigated ADA activity in lymphocyte-rich peripheral blood mononuclear cells (PBMCs) in the absence of disease. The viability of lymphocyte-rich PBMCs isolated from humans and kept in 0.9% saline solution at 4-8°C was analyzed over 20 h. The incubation time and biochemical properties of the enzyme, such as its Michaelis-Menten constant (Km) and maximum velocity (Vmax), were characterized through the liberation of ammonia from the adenosine substrate. Additionally, the presence of ADA protein on the lymphocyte surface was determined by flow cytometry using an anti-CD26 monoclonal human antibody, and the PBMCs showed long-term viability after 20 h. The ADA enzymatic activity was linear from 15 to 120 min of incubation, from 2.5 to 12.5 µg of protein, and pH 6.0 to 7.4. The Km and Vmax values were 0.103±0.051 mM and 0.025±0.001 nmol NH3·mg-1·s-1, respectively. Zinc and erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA) inhibited enzymatic activity, and substrate preference was given to adenosine over 2'-deoxyadenosine and guanosine. The present study provides the biochemical characterization of ADA in human lymphocyte-rich PBMCs, and indicates the appropriate conditions for enzyme activity quantification.

Propofol at Single Bolus and Continuous Rate Infusion Significantly Increases Serum Triglycerides, but not Cholesterol, In Healthy Bitches Undergoing Elective Ovariohysterectomy.

This study aimed to investigate the effects of a single bolus and continuous rate infusion (CRI) of 1% propofol on cholesterol and triglyceride levels of healthy bitches undergoing elective ovariohysterectomy. 10 healthy bitches undergoing elective ovariohysterectomy had blood samples obtained at baseline (TB), 15 minutes following premedication with acepromazine and morphine (TPM), after an intravenous bolus of propofol (induction to anesthesia, TIND) and following 90 minutes of CRI of propofol started at 0.4 mg kg-1 min-1 and adjusted according to individual requirements (TCRI). Data were initially tested for normality using the Shapiro-Wilk test, and comparisons were performed using Friedman followed by Dunn post-hoc test. Serum cholesterol levels significantly decreased at TIND and TCRI (median [min-max] 201 mg dL-1 [111-234 mg dL-1], and 215 mg dL-1 [111-239 mg dL-1]), respectively, compared with TB (232 [128-245 mg dL-1]) and TPM (206 [115-255 mg dL-1]). No differences were found between TIND and TCRI. Triglyceride levels increased significantly at TIND (120 [67-231 mg dL-1]) and TCRI (229 [73-549 mg dL-1]) compared with TPM (36 [51-29 mg dL-1]), and TCRI compared with TB. In conclusion, 1% propofol lipid emulsion significantly increases serum triglycerides and causes lipemia in healthy dogs at a single bolus or CRI.

Carers' and paediatric dentists' perceptions of children's pain during restorative treatment.

PURPOSE: Parents/carers' and dentists' evaluations are important when assessing young children's pain. However, there is little evidence on agreement regarding children's pain according to proxy reports. The aims of this cross-sectional study were to investigate the agreement among paediatric dentists and parents/carers about children's pain during treatment and the association between the reporting of pain and child behaviour. METHODS: Participants were 81 parents/carers of uncooperative children undergoing restorative treatment, and five paediatric dentists. Pain during dental treatment was assessed after dental procedures using the Visual Analogue Scale (0-4 mm: no pain; 5-44 mm: mild pain; 45-74 mm: moderate pain; 75-100 mm: severe pain). Child behaviour was assessed by calibrated researchers using the Ohio State University Behavioural Scale. The agreement between respondents about a child's pain was evaluated using the weighted kappa test. The association between the pain report and child behaviour was verified using the Kruskal-Wallis and Mann-Whitney tests. RESULTS: Parents/carers (36, 44.4%) and paediatric dentists (40, 49.4%) reported that children felt mild pain in all sessions. The parents/carers reported that the children experienced higher pain intensities compared to paediatric dentists. The agreement between respondents was slight (weighted Kappa < 0.20). Higher pain intensities were more frequent when the children's behaviour was uncooperative. CONCLUSION: Parents/carers and paediatric dentists showed slight agreement regarding the pain felt by children in dental treatment. Pain proxy reporting in children is influenced by the children's behaviour.

Diagnosis and treatment of confirmed and suspected primary hyperparathyroidism in equids: 17 cases (1999-2016).

BACKGROUND: Primary hyperparathyroidism is uncommon in equids. OBJECTIVES: To describe the diagnostic findings and efficacy of treatment in equids with primary hyperparathyroidism. STUDY DESIGN: Retrospective case series describing 16 horses and one mule. METHODS: Cases were identified by retrospective review of records at Cornell University and via an ACVIM listserv query. Inclusion criteria were an equid with hypercalcemia, normal renal function and high parathyroid hormone (PTH) or histopathological diagnosis of a parathyroid adenoma. Equids with normal PTH and PTH-related protein (PTHrP) in the face of hypercalcemia were included as suspect cases. RESULTS: The most common presenting complaints were weight loss (12/17) and hypercalcemia (10/17). PTH was above reference range in 12/17 cases. Suspected parathyroid tumours were localised in 12/14 equids imaged using ultrasonography alone (2/3), technetium 99m Tc sestamibi scintigraphy alone (1/1) or both modalities (9/10). Three horses did not have imaging performed. Surgical exploration successfully excised tumours in six of 10 cases. Five were located at the thoracic inlet, and surgery resulted in complete cure. One tumour was excised from the thyroid lobe, and the horse remained hypercalcemic. Four other cases explored surgically, four treated medically and three that were not treated also remained hypercalcemic. MAIN LIMITATIONS: The small study size prohibited statistical analysis. CONCLUSIONS: Parathyroid adenomas in equids can be successfully localised with ultrasonography and scintigraphy. Surgical excision appears more likely to be successful for single gland disease at the thoracic inlet.

Plasma and pulmonary fluid endothelin in horses with seasonal recurrent airway obstruction.

BACKGROUND: Summer pasture-associated recurrent airway obstruction (SPA-RAO), a seasonal airway obstructive disease of horses, is characterized by clinical exacerbation after exposure to pasture during warm months of the year. Endothelin (ET)-1, potent bronchoconstrictor, mitogen, secretagogue, and proinflammatory mediator, has been implicated in the pathogenesis of asthma and equine heaves. HYPOTHESIS: Immunoreactive ET-1 concentrations increase during clinical exacerbation and return to basal values during periods of disease remission. ANIMALS: Twelve horses, 6 affected with SPA-RAO and 6 nonaffected. METHODS: Prospective, observational study. Bronchoalveolar lavage fluid (BALF), arterial and venous plasma samples, and clinical variables were obtained from affected horses during clinical exacerbation and remission. Samples and data of nonaffected horses were collected during the summer and winter on dates similar to affected horses. Immunoreactive ET-1 was determined using a commercial ELISA. RESULTS: The median and range ET-1 concentrations (pg/ml) in arterial (1.3, 0.7-1.8) and venous (1.3, 1.2-1.7) plasma and in BALF (0.3, 0.2-0.4), and pulmonary epithelial lining fluid (PELF) (25.5, 21-50) were greater in affected horses during clinical exacerbation compared with remission (P < .01). The concentrations of immunoreactive ET-1 were greater in affected horses during clinical exacerbation compared with nonaffected horses (P < .05). CONCLUSIONS AND CLINICAL IMPORTANCE: During clinical exacerbation of SPA-RAO, ET-1 is increased in circulation and pulmonary secretions. Intervention with ET receptor antagonists should provide further information on the role of ET-1 in SPA-RAO.

Presumed Neuroglycopenia Caused by Severe Hypoglycemia in Horses.

BACKGROUND: Neuroglycopenia refers to a shortage of glucose in the brain resulting in neuronal dysfunction and death if left untreated. Presumed neuroglycopenia has not been described in horses. OBJECTIVE: To report neurological signs in horses with presumed neuroglycopenia as the result of severe hypoglycemia. ANIMALS: Ninety horses (hours to 28 years of age) diagnosed with hypoglycemia (blood glucose concentration < 75 mg/dL [< 4.2 mmol/L]). METHODS: Retrospective study. Electronic medical records were searched. Signalment, history, complaint, clinical signs, laboratory findings including CSF analysis, electroencephalogram, clinical or definitive diagnosis, and outcome were recorded. Kruskal-Wallis analysis of variance and logistic regression were used to investigate association between blood glucose concentration and data extracted. Statistical significance was set at P < 0.05. RESULTS: Thirty-eight and 52 horses had mild (50-74 mg/dL [2.8-4.1 mmol/L]), and severe hypoglycemia (< 50 mg/dL [< 2.8 mmol/L]), respectively. Most common causes of hypoglycemia included liver and gastrointestinal (40%) disease, sepsis (33%), neoplasia (7%), and insulin-induced (4%). Most common neurologic deficits included obtundation (100%), seizures (42%), and disorientation (22%). CSF-glucose was severely low (mean 2.5 mg/dL [0.1 mmol/L], median 0 mg/dL). Paroxysmal discharges in support of seizures were identified in the occipital (visual) and parietal (closest to temporal-auditory) cortical regions upon EEG examination (8/8 horses). CONCLUSIONS AND CLINICAL IMPORTANCE: Neuroglycopenia is presumed to occur in horses as the result of severe hypoglycemia. Subclinical seizures, and intermittent blindness and deafness of cortical origin can occur. Severe altered state of consciousness and seizures can be observed at a blood glucose cut-off value of < 42 mg/dL (< 2.3 mmol/L).

Biochemical characterization of adenosine deaminase (CD26 EC 3. 5. 4. 4) activity in human lymphocyte-rich peripheral blood mononuclear cells

The conversion of adenosine to inosine is catalyzed by adenosine deaminase (ADA) (EC 3.5.4.4), which has two isoforms in humans (ADA1 and ADA2) and belongs to the zinc-dependent hydrolase family. ADA modulates lymphocyte function and differentiation, and regulates inflammatory and immune responses. This study investigated ADA activity in lymphocyte-rich peripheral blood mononuclear cells (PBMCs) in the absence of disease. The viability of lymphocyte-rich PBMCs isolated from humans and kept in 0.9% saline solution at 4-8°C was analyzed over 20 h. The incubation time and biochemical properties of the enzyme, such as its Michaelis-Menten constant (Km) and maximum velocity (Vmax), were characterized through the liberation of ammonia from the adenosine substrate. Additionally, the presence of ADA protein on the lymphocyte surface was determined by flow cytometry using an anti-CD26 monoclonal human antibody, and the PBMCs showed long-term viability after 20 h. The ADA enzymatic activity was linear from 15 to 120 min of incubation, from 2.5 to 12.5 µg of protein, and pH 6.0 to 7.4. The Km and Vmax values were 0.103±0.051 mM and 0.025±0.001 nmol NH3·mg-1·s-1, respectively. Zinc and erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA) inhibited enzymatic activity, and substrate preference was given to adenosine over 2′-deoxyadenosine and guanosine. The present study provides the biochemical characterization of ADA in human lymphocyte-rich PBMCs, and indicates the appropriate conditions for enzyme activity quantification.

Influence of different periods of pre-slaughter fasting on microbiological quality of bullfrog carcasses (Lithobates catesbeianus) / [Influência de diferentes períodos de jejum pré-abate na qualidade microbiológica de carcaças de rã-touro (Lithobates catesbeianus)]

The aim of this study was to evaluate the influence of different periods of pre-slaughter fasting (F1: 2 to 24 hours and F2: 48 to 72 hours) on the counts of hygiene indicator microorganisms and the presence of Salmonella spp. in carcasses of bullfrogs. Two different stages of the slaughter process were analyzed: after bleeding (A) and after the final carcasses cleaning (B). Samples from each fasting period were analyzed to count hygiene indicator microorganisms (n=30) and Salmonella spp. (n=140). For aerobic mesophilic microorganisms, the variation in fasting periods caused a reduction of 0.69 log10 CFU / g (P<0.05) in F2 when compared to F1 at point B of the slaughter. Coliforms at 35º C and Escherichia coli showed no differences (P >0.05) between the fasting analyzed periods. Considering the presence of E. coli, it was observed that F2 resulted in a reduction of 30% (P<0.05) positivity on point B. For Salmonella spp., the results showed that F2 contributed to an 11.5% reduction in the presence of this bacteria at point B. (P<0.05). Therefore, it is concluded that 48 to 72 hours of pre-slaughter fasting resulted in a positive impact on the microbiological quality of bullfrog carcasses.(AU)

O objetivo deste estudo foi avaliar a influência de diferentes períodos de jejum pré-abate (F1: duas a 24 horas e F2: 48 a 72 horas) nas contagens de micro-organismos indicadores de higiene e na presença de Salmonella spp. em carcaças de rãs-touro. Foram analisadas duas etapas do processo de abate: após a sangria (A) e após a toalete final da carcaça (B). As amostras de cada período de jejum foram utilizadas para contagem de indicadores de higiene (n = 30) e Salmonella spp. (n = 140). Para aeróbios mesófilos, a variação no tempo de jejum causou uma redução de 0,69 log10 UFC/g (P<0,05) em F2 quando comparado a F1 na etapa B do abate. Os coliformes a 35ºC e Escherichia coli não apresentaram diferenças (P>0,05) entre os dois períodos de jejum analisados. Considerando a presença de E. coli, F2 resultou em uma redução de 30% (P<0,05) de positividade na etapa B. Para Salmonella spp., os resultados mostraram que F2 contribuiu para uma redução de 11,5% na presença desse micro-organismo na etapa B. Portanto, conclui-se que 48 a 72 horas de jejum pré-abate tiveram um impacto positivo na qualidade microbiológica das carcaças de rã-touro.(AU)

Tests of intestinal function.

The most important tests for investigating the functions of the small bowel are faecal-fat analysis, the determination of xylose tolerance, vitamin-B12 absorption, and 14C-glycoholate transport, barium examination of the small bowel, and small bowel biopsy. With these tests, most disorders of digestion and of absorption can be adequately investigated and diagnosed.

Comparative molecular characterization of Corynebacterium pseudotuberculosis of different origin.

Ribotyping and susceptibility to 17 antimicrobial agents were used to compare 37 isolates of Corynebacterium pseudotuberculosis (28 from horses, 1 from cattle, 3 from sheep and 5 from goats) derived from various types of lesions, and different geographic locations. According to the presence of nitrate reductase, all but one isolate from horses reduced nitrate (nitrate-positive), whereas all isolates from sheep and goats were unable to reduce nitrate (nitrate-negative). The ribotype of the nitrate-negative isolate from a horse with ulcerative lymphangitis was identical to all the other isolates from horses, and different than the ribotype of nitrate-negative isolates from sheep and goats. Ribotyping with one of the restriction endonucleases, Apa 1, revealed differences between, but not within, the two biotypes. However, ribotyping with Pst 1 endonuclease revealed one variant within the equine biotype and one variant within the ovine biotype. The minimum inhibitory concentration (MIC; microgram/ml) of antimicrobial agents against isolates from nitrate-negative and nitrate-positive groups was very similar, with the exception of isolates from sheep and goats which had a higher MIC for amikacin than isolates from horses and cattle.

Tumor necrosis factor-alpha production and disease severity after immunization with enriched major core protein (p26) and/or infection with equine infectious anemia virus.

Cardinal features of equine infectious anemia (EIA) include fever, hemolytic anemia and thrombocytopenia during the acute phase of the disease, and cachexia and anemia seen during the chronic phase. These signs are thought to result from the release of inflammatory cytokines such as TNF-alpha. In order to determine if TNF-alpha has a role in the pathogenesis of acute EIA and vaccine-induced disease enhancement, we measured plasma concentrations of TNF-alpha in ponies immunized with virus enriched major core protein-p26 and/or experimentally infected with EIAV. Naturally infected inapparent EIAV carriers were also studied. TNF-alpha levels were determined by means of a WEHI 164, clone 13 cytotoxicity assay. We show a significant positive temporal correlation between TNF-alpha levels, severity of symptoms (fever and thrombocytopenia) and viremia. Furthermore, TNF-alpha levels also correlate with strain virulence and the disease enhancement seen in vaccinated ponies. Of this group of animals, those challenged with a heterologous virulent strain presented the most unfavorable outcome as well as the highest levels of TNF-alpha and viremia. The TNF-alpha activity observed in the bioassay was completely abrogated by a polyclonal rabbit anti-human TNF-alpha antiserum, thus confirming the specificity of the plasma cytotoxicity. Our observations indicate that TNF-alpha production correlates with the outcome of infection with EIAV.

Value of a therapeutic trial to diagnose gastroesophageal reflux disease: step up versus step down therapy.

The 1992 Canadian Association of Gastroenterology consensus conference on gastroesophageal reflux disease (GERD) recommended a therapeutic trial of H2 receptor antagonists as a cost effective approach to the management of patients with typical symptoms of GERD. Omeprazole, with its increased potency and efficacy of acid suppression, appears to be the ideal diagnostic test therapy for GERD. However, there is little evidence in the literature to support this approach. Omeprazole has the potential to mask other disorders such as peptic ulcer disease, thereby delaying appropriate testing for and eradication of Helicobacter pylori. Therefore, omeprazole therapeutic trials should be used with caution in the diagnosis of GERD. The conventional step up therapy is the least costly and reasonably effective approach to treat the majority of patients with mild to moderate symptoms of GERD. For patients who fail therapy or have complications of GERD, the recently proposed step down therapy is probably more effective and appropriate. As physicians become more comfortable with the long term use of proton pump inhibitors, step down therapy may well replace the more conservative step up approach to therapy.

The Second Canadian Consensus Conference on the Management of Patients with Gastroesophageal Reflux Disease.

The Second Canadian Consensus Conference on the Management of Patients with Gastroesophageal Reflux Disease (GERD) was organized by the Canadian Association of Gastroenterology to address major advances in the understanding of the pathophysiology of GERD, to review the new methods of investigation and therapy introduced since the first conference in 1992 and to examine the issue of relevant health economics. The changes that have taken place over the past four years have been sufficiently dramatic to necessitate reassessment of the recommendations made following the first conference. The second conference dealt with the investigation and treatment of uncomplicated GERD and the complex issues of esophageal and extraesophageal complications such as chest pain, Barrett's esophagus, and reflux-related pulmonary and laryngeal disorders. The role of laparoscopic surgery was also discussed. A decision tree for investigation and treatment of patients with GERD was developed. The 38 participants represented a broad spectrum of experience, location of practice and special interests. The distribution of participants conformed to the recommendations of the Canadian Medical Association guidelines for consensus documents in that there should be input from all possible interested parties. A list of the state-of-the-art lectures presented during the conference, the small group sessions, the session chairpersons and participants are appended to this document. CONCLUSIONS. UNCOMPLICATED GERD: GERD with alarm symptoms must be investigated immediately. There was no consensus about when to investigate uncomplicated GERD, ie, whether to perform endoscopy immediately or after initial therapy fails. There was controversy regarding 'step up' (H2 receptor antagonist [H2RA] or prokinetic [PK] first therapy) versus 'step down' therapy (proton pump inhibitor [PPI] first therapy). The majority decision was for short term 'step up' therapy and investigation if symptoms do not improve or recur. Maintenance therapy should be carried out with the initial therapy that was effective. H2RAs and PKs may suffice for maintenance therapy in milder GERD; however, for severe esophagitis, PPIs should be used. SURGERY: Indications for laparoscopic surgery should be the same as for conventional antireflux operations. NONCARDIAC ANGINA-LIKE CHEST PAIN: After exclusion of nonesophageal causes, the majority decided that eight weeks of therapy with a PPI should be performed, while some suggested work-up before a therapeutic test. In the absence of response or recurrence, esophagogastroduodenoscopy (EGD) and, depending on the circumstances, 24 h ambulatory pH/motility may be indicated. BARRETT'S ESOPHAGUS: Only patients who, in case of future discovery of cancer or dysplasia, are able or willing to undergo therapy should have surveillance. In the absence of dysplasia EGD should be performed every two years, and in the presence of mild dysplasia every three to six months. All agreed that for severe dysplasia, esophagectomy or poor risk patients, esophageal mucosal ablation is indicated. ESTRAESOPHAGEAL COMPLICATONS (EECs): Asthma, chronic cough and posterior laryngitis were considered EECs. Although PPIs may decrease symptoms, improvement alone is not diagnostic of the presence of EEC. Ambulatory pH studies with two pH probes or ambulatory pH/motility may be useful in establishing causation. HEALTH ECONOMICS: There are limited data for an economic comparison among the different drugs or between medical and surgical therapy.