Probiotics for the postoperative management of term neonates after gastrointestinal surgery.

BACKGROUND: The intestinal microflora has an essential role in providing a barrier against colonisation of pathogens, facilitating important metabolic functions, stimulating the development of the immune system, and maintaining intestinal motility. Probiotics are live microorganisms that can be administered to supplement the gut flora. Neonates who have undergone gastrointestinal surgery are particularly susceptible to infectious complications in the postoperative period. This may be partly due to a disruption of the integrity of the gut and its intestinal microflora. There may be a role for probiotics in reducing the incidence of sepsis and improving intestinal motility, thus reducing morbidity and mortality and improving enteral feeding in neonates in the postoperative period. OBJECTIVES: To evaluate the efficacy and safety of administering probiotics after gastrointestinal surgery for the postoperative management of neonates born from 35 weeks of gestation. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, and trial registries in August 2023. We checked reference lists of included studies and relevant systematic reviews for additional studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that investigated the postoperative administration of oral probiotics versus placebo or no treatment in neonates born from 35 weeks of gestation who had one or more gastrointestinal surgical procedures. We applied no restrictions regarding the type or dosage of probiotics or the duration of treatment. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods, and we used GRADE to assess the certainty of evidence. MAIN RESULTS: We identified one RCT that recruited 61 neonates with a gestational age of 35 weeks or more. All infants were admitted to a neonatal intensive care unit and had surgery for gastrointestinal pathologies. There may be little or no difference in proven sepsis (positive bacterial culture, local or systemic) between infants who receive probiotics compared with those who receive placebo (odds ratio (OR) 0.64, 95% confidence interval (CI) 0.16 to 2.55; 61 infants; low-certainty evidence). Probiotics compared to placebo may have little or no effect on time to full enteral feeds (mean difference (MD) 0.63 days, 95% CI -4.02 to 5.28; 61 infants; low-certainty evidence). There were no reported deaths prior to discharge from hospital in either study arm. Two weeks after supplementation, the infants who received probiotics had a substantially higher relative abundance of non-pathogenic intestinal microflora (Bifidobacteriaceae) than those who received placebo (MD 38.22, 95% CI 28.40 to 48.04; 39 infants; low-certainty evidence). AUTHORS' CONCLUSIONS: This review provides low-certainty evidence from one small RCT that probiotics compared to placebo have little or no effect on the risk of proven sepsis (positive bacterial culture, local or systemic) or time to full-enteral feeds in neonates who have undergone gastrointestinal surgery. Probiotics may substantially increase the abundance of beneficial bacterial in the intestine of these neonates, but the clinical implications of this finding are unknown. There is a need for adequately powered RCTs to assess the role of probiotics in this population. We identified two ongoing studies. As neither reported the gestational age of prospective study participants, we are unsure if they will be eligible for inclusion in this review.

LMA® Gastro™ Airway for endoscopic retrograde cholangiopancreatography: a retrospective observational analysis.

BACKGROUND: Various airway techniques have been employed for endoscopic procedures, with an aim to optimise patient outcomes by improving airway control and preventing hypoxia whilst avoiding the need for intubation. The LMA® Gastro™ Airway, a novel dual channel supraglottic airway technique, has been described as such a device. Its utility alongside sedation with low flow nasal cannula and general anaesthesia (GA) with intubation for endoscopic retrograde cholangiopancreatography (ERCP) procedures was evaluated. METHODS: Details of all the ERCPs performed in our institution from March 2017 to June 2018 were carefully recorded in the patients' electronic case records. Data on the successful completion of ERCP through LMA® Gastro™ Airway; any difficulty encountered by the gastroenterologists; and adverse events were recorded. Episodes of hypoxia (SpO2 < 92%) and haemodynamic parameters were compared across the three groups: LMA® Gastro™ vs. sedation with low flow nasal cannula vs. GA with an endotracheal tube (ETT). RESULTS: One hundred seventy-seven ERCP procedures were performed during the study period. The LMA® Gastro™ Airway was employed in 64 procedures (36%) on 59 patients. Of these 64 procedures, ERCP was successfully completed with LMA® Gastro™ Airway in 63 (98%) instances, with only one case requiring conversion to an endotracheal tube. This instance followed difficulty in negotiating the endoscope through LMA® Gastro™ Airway. No episodes of hypoxia or hypercapnia were documented in both LMA® Gastro™ and GA with ETT groups. One sedation case with nasal cannula was noted to have hypoxia. Adverse intraoperative events were recognised in 2 cases of LMA® Gastro™: one had minimal blood stained secretions from the oral cavity that resolved with suctioning; the other developed mild laryngospasm which resolved spontaneously within a few minutes. CONCLUSION: In patients undergoing ERCP, the LMA® Gastro™ airway demonstrated a high success rate for ERCP completion. Ventilation was well maintained with minimal intraoperative and postoperative adverse events. This technique may have a role in higher risk groups such as high ASA (American Society of Anesthesiologists) status, or those with potential airway difficulties such as high body mass index and those with known or suspected sleep apnoea.

Mesh versus non-mesh for inguinal and femoral hernia repair.

BACKGROUND: This is an update of a Cochrane Review first published in 2001.Hernias are protrusions of all or part of an organ through the body wall that normally contains it. Groin hernias include inguinal (96%) and femoral (4%) hernias, and are often symptomatic with discomfort. They are extremely common, with an estimated lifetime risk in men of 27%. Occasionally they may present as emergencies with complications such as bowel incarceration, obstruction and strangulation. The definitive treatment of all hernias is surgical repair, inguinal hernia repair being one of the most common surgical procedures performed. Mesh (hernioplasty) and the traditional non-mesh repairs (herniorrhaphy) are commonly used, with an increasing preference towards mesh repairs in high-income countries. OBJECTIVES: To evaluate the benefits and harms of different inguinal and femoral hernia repair techniques in adults, specifically comparing closure with mesh versus without mesh. Outcomes include hernia recurrence, complications (including neurovascular or visceral injury, haematoma, seroma, testicular injury, infection, postoperative pain), mortality, duration of operation, postoperative hospital stay and time to return to activities of daily living. SEARCH METHODS: We searched the following databases on 9 May 2018: Cochrane Colorectal Cancer Group Specialized Register, Cochrane Central Register of Controlled Trials (Issue 1), Ovid MEDLINE (from 1950), Ovid Embase (from 1974) and Web of Science (from 1900). Furthermore, we checked the WHO International Clinical Trials Registry Platform (ICTRP) and ClinicalTrials.gov for trials. We applied no language or publication restrictions. We also searched the reference lists of included trials and review articles. SELECTION CRITERIA: We included randomised controlled trials of mesh compared to non-mesh inguinal or femoral hernia repairs in adults over the age of 18 years. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Where available, we collected information on adverse effects. We presented dichotomous data as risk ratios, and where possible we calculated the number needed to treat for an additional beneficial outcome (NNTB). We presented continuous data as mean difference. Analysis of missing data was based on intention-to-treat principles, and we assessed heterogeneity using an evaluation of clinical and methodological diversity, Chi2 test and I2 statistic. We used GRADE to assess the quality of evidence for each outcome. MAIN RESULTS: We included 25 studies (6293 participants) in this review. All included studies specified inguinal hernias, and two studies reported that femoral hernias were included.Mesh repair probably reduces the risk of hernia recurrence compared to non-mesh repair (21 studies, 5575 participants; RR 0.46, 95% CI 0.26 to 0.80, I2 = 44%, moderate-quality evidence). In absolute numbers, one hernia recurrence was prevented for every 46 mesh repairs compared with non-mesh repairs. Twenty-four studies (6293 participants) assessed a wide range of complications with varying follow-up times. Neurovascular and visceral injuries were more common in non-mesh repair groups (RR 0.61, 95% CI 0.49 to 0.76, I2 = 0%, NNTB = 22, high-quality evidence). Wound infection was found slightly more commonly in the mesh group (20 studies, 4540 participants; RR 1.29, 95% CI 0.89 to 1.86, I2 = 0%, NNTB = 200, low-quality evidence). Mesh repair reduced the risk of haematoma compared to non-mesh repair (15 studies, 3773 participants; RR 0.88, 95% CI 0.68 to 1.13, I2 = 0%, NNTB = 143, low-quality evidence). Seromas probably occur more frequently with mesh repair than with non-mesh repair (14 studies, 2640 participants; RR 1.63, 95% CI 1.03 to 2.59, I2 = 0%, NNTB = 72, moderate-quality evidence), as does wound swelling (two studies, 388 participants; RR 4.56, 95% CI 1.02 to 20.48, I2 = 33%, NNTB = 72, moderate-quality evidence). The comparative effect on wound dehiscence is uncertain due to wide confidence intervals (two studies, 329 participants; RR 0.55, 95% CI 0.12 to 2.48, I2 = 37% NNTB = 77, low-quality evidence). Testicular complications showed nearly equivocal results; they probably occurred slightly more often in the mesh group however the confidence interval around the effect was wide (14 studies, 3741 participants; RR 1.06, 95% CI 0.63 to 1.76, I2 = 0%, NNTB = 2000, low-quality evidence). Mesh reduced the risk of postoperative urinary retention compared to non-mesh (eight studies, 1539 participants; RR 0.53, 95% CI 0.38 to 0.73, I2 = 56%, NNTB = 16, moderate-quality evidence).Postoperative and chronic pain could not be compared due to variations in measurement methods and follow-up time (low-quality evidence).No deaths occurred during the follow-up periods reported in the seven studies (2546 participants) reporting this outcome (high-quality evidence).The average operating time was longer for non-mesh repairs by a mean of 4 minutes 22 seconds, despite wide variation across the studies regarding size and direction of effect, thus this result is uncertain (20 studies, 4148 participants; 95% CI -6.85 to -1.60, I2= 97%, very low-quality evidence). Hospital stay may be shorter with mesh repair, by 0.6 days (12 studies, 2966 participants; 95% CI -0.86 to -0.34, I2 = 98%, low-quality evidence), and participants undergoing mesh repairs may return to normal activities of daily living a mean of 2.87 days sooner than those with non-mesh repair (10 studies, 3183 participants; 95% CI -4.42 to -1.32, I2 = 96%, low-quality evidence), although the results of both these outcomes are also limited by wide variation in the size and direction of effect across the studies. AUTHORS' CONCLUSIONS: Mesh and non-mesh repairs are effective surgical approaches in treating hernias, each demonstrating benefits in different areas. Compared to non-mesh repairs, mesh repairs probably reduce the rate of hernia recurrence, and reduce visceral or neurovascular injuries, making mesh repair a common repair approach. Mesh repairs may result in a reduced length of hospital stay and time to return to activities of daily living, but these results are uncertain due to variation in the results of the studies. Non-mesh repair is less likely to cause seroma formation and has been favoured in low-income countries due to low cost and reduced availability of mesh materials. Risk of bias in the included studies was low to moderate and generally handled well by study authors, with attention to details of allocation, blinding, attrition and reporting.

Association between the elderly frequent attender to the emergency department and 30-day mortality: A retrospective study over 10 years.

BACKGROUND: To determine if elderly frequent attenders are associated with increased 30-day mortality, assess resource utilization by the elderly frequent attenders and identify associated characteristics that contribute to mortality. METHODS: Retrospective observational study of electronic clinical records of all emergency department (ED) visits over a 10-year period to an urban tertiary general hospital in Singapore. Patients aged 65 years and older, with 3 or more visits within a calendar year were identified. Outcomes measured include 30-day mortality, admission rate, admission diagnosis and duration spent at ED. Chi-square-tests were used to assess categorical factors and Student t-test was used to assess continuous variables on their association with being a frequent attender. Univariate and multivariate logistic regressions were conducted on all significant independent factors on to the outcome variable (30-day mortality), to determine factor independent odds ratios of being a frequent attender. RESULTS: 1.381 million attendance records were analyzed. Elderly patients accounted for 25.5% of all attendances, of which 31.3% are frequent attenders. Their 30-day mortality rate increased from 4.0% in the first visit, to 8.8% in the third visit, peaking at 10.2% in the sixth visit. Factors associated with mortality include patients with neoplasms, ambulance utilization, male gender and having attended the ED the previous year. CONCLUSION: Elderly attenders have a higher 30-day mortality risk compared to the overall ED population, with mortality risk more marked for frequent attenders. This study illustrates the importance and need for interventions to address frequent ED visits by the elderly, especially in an aging society.

Data-Driven Approach to Defining the Emergency Department Frequent Attender Using a Cohort of 10 Years.

AIMS: To identify, based on the measure of resource utilization, the number of visits per calendar year that defines the emergency department (ED) frequent attender; and examine for significant trends in patient characteristics and outcomes which may support the use of our definition. MATERIALS AND METHODS: We conducted a retrospective observational study of electronic clinical records of all ED visits over a 10-year period from January 2005 to December 2014 to an urban tertiary general hospital. We defined the ED frequent attender based on the number of ED attendances per calendar year which would yield a patient group representing more than 20% of all patient visits. Chi-square tests were conducted on each categorical factor individually to assess if they were independent of time, and the Student's t-test was used to assess continuous variables on their association with being a frequent attender. RESULTS: 1.381 million attendance records were analyzed. Patients who attended three or more times per year accounted for about 22.1% of all attendances and were defined as frequent attenders. They were associated with higher triage acuity, complex chronic illnesses, greater 30-day mortality for patients with three to six visits, and increased markers of resource utilization, such as ambulance use (15.5% vs. 11.6%), time to disposition (180 vs. 155 minutes), admissions rate (47.4% vs. 30.7%) and inpatient length of stay (6 days vs. 4 days). All p values were statistically significant (p < 0.001). CONCLUSION: We have demonstrated a data-driven approach to defining an ED frequent attender. Frequent attenders are associated with increased resource utilization, more complex illness and may be associated with greater 30-day mortality rates.

Haemophilus influenzae oral vaccination for preventing acute exacerbations of chronic bronchitis and chronic obstructive pulmonary disease.

BACKGROUND: Chronic bronchitis and chronic obstructive pulmonary disease (COPD) are serious conditions in which patients are predisposed to viral and bacterial infections resulting in potentially fatal acute exacerbations. Chronic obstructive pulmonary disease is defined as a lung disease characterised by obstruction to lung airflow that interferes with normal breathing. Antibiotic therapy has not been particularly useful in eradicating bacteria such as non-typeable Haemophilus influenzae (NTHi) because they are naturally occurring flora of the upper respiratory tract in many people. However, they can cause opportunistic infection. An oral NTHi vaccine has been developed to protect against recurrent infective acute exacerbations in chronic bronchitis. OBJECTIVES: To assess the effectiveness of an oral, whole-cell NTHi vaccine in protecting against recurrent episodes of acute exacerbations of chronic bronchitis and COPD in adults. To assess the effectiveness of NTHi vaccine in reducing NTHi colonising the respiratory tract during recurrent episodes of acute exacerbations of COPD. SEARCH METHODS: We searched the following databases: the Cochrane Central Register of Controlled Trials (CENTRAL) (2017, Issue 1), MEDLINE (1946 to January 2017), Embase (1974 to January 2017), CINAHL (1981 to January 2017), LILACS (1985 to January 2017), and Web of Science (1955 to January 2017). We also searched trials registries and contacted authors of trials requesting unpublished data. SELECTION CRITERIA: We included randomised controlled trials comparing the effects of an oral monobacterial NTHi vaccine in adults with recurrent acute exacerbations of chronic bronchitis or COPD when there was overt matching of the vaccine and placebo groups on clinical grounds. The selection criteria considered populations aged less than 65 years and those older than 65 years. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data from original records and publications for incidence and severity of bronchitis episodes and carriage rate of NTHi measured in the upper respiratory tract, as well as data relevant to other primary and secondary outcomes. MAIN RESULTS: We identified six placebo-controlled randomised controlled trials with a total of 557 participants. These trials investigated the efficacy of enteric-coated, killed preparations of H influenzae in populations prone to recurrent acute exacerbations of chronic bronchitis or COPD. The vaccine preparation and immunisation regimen in all trials consisted of at least three courses of formalin-killed H influenzae in enteric-coated tablets taken at intervals (e.g. days 0, 28, and 56). Each course generally consisted of two tablets taken after breakfast over three consecutive days. In all cases the placebo groups took enteric-coated tablets containing glucose. Risk of bias was moderate across the studies, namely due to the lack of information provided about methods and inadequate presentation of results.Meta-analysis of the oral NTHi vaccine showed a small, non-statistically significant reduction in the incidence of acute exacerbations of chronic bronchitis or COPD (risk ratio (RR) 0.79, 95% confidence interval (CI) 0.57 to 1.10; P = 0.16). There was no significant difference in mortality rate between the vaccine and placebo groups (odds ratio (OR) 1.62, 95% CI 0.63 to 4.12; P = 0.31).We were unable to meta-analyse the carriage levels of NTHi in participants as each trial reported this result using different units and tools of measurement. Four trials showed no significant difference in carriage levels, while two trials showed a significant decrease in carriage levels in the vaccinated group compared with the placebo group.Four trials assessed severity of exacerbations measured by requirement for antibiotics. Three of these trials were comparable and when meta-analysed showed a statistically significant 80% increase in antibiotic courses per person in the placebo group (RR 1.81, 95% CI 1.35 to 2.44; P < 0.001). There was no significant difference between the groups with regard to hospital admission rates (OR 0.96, 95% CI 0.13 to 7.04; P = 0.97). Adverse events were reported in five trials but were not necessarily related to the vaccine; a point estimate is suggestive that they occurred more frequently in the vaccine group, however this result was not statistically significant (RR 1.43, 95% CI 0.70 to 2.92; P = 0.87). Quality of life was not meta-analysed but was reported in two trials, with results at six months showing an improvement in quality of life in the vaccinated group (scoring at least two points better than placebo). AUTHORS' CONCLUSIONS: Analyses demonstrate that NTHi oral vaccination of people with recurrent exacerbations of chronic bronchitis or COPD does not yield a significant reduction in the number and severity of exacerbations. Evidence was mixed, and the individual trials that showed a significant benefit of the vaccine are too small to advocate widespread oral vaccination of people with COPD.

Full medical program fees and medical student career intention.

OBJECTIVE: To explore the future career preferences of Commonwealth-supported place (CSP) and full-fee paying (FFP) medical students in Australia. DESIGN, SETTING AND PARTICIPANTS: Data from the Medical Schools Outcomes Database and Longitudinal Tracking (MSOD) Project exit questionnaire for CSP and FFP students who graduated between 2008 and 2011 were analysed using logistic regression. The influence of age, sex, marital status, rural background and fee-paying status on future career preference were explored. MAIN OUTCOME MEASURE: Future career preference (location and specialty) at graduation. RESULTS: Compared with CSP students, domestic FFP students were more likely to nominate as their first preference both urban locations (odds ratio [OR], 5.58; 95% CI, 2.04-15.26; P < 0.001) and higher-income specialties (OR, 1.37; 95% CI, 1.07-1.75; P < 0.05), and less likely to nominate as their first preference in-need specialties (OR, 0.72; 95% CI, 0.52-1.00; P < 0.05), specifically general practice (OR, 0.71; 95% CI, 0.52-0.99; P < 0.05). There was a significant domestic FFP student by marital status interaction effect, such that domestic FFP students who were married or partnered on exit from medical school were more likely to prefer a rural location (OR, 0.64; 95% CI, 0.44-0.95; P < 0.05). Also, students who were married or partnered were less likely to select a one of the higher-income specialties as their first preference (OR, 0.77; 95% CI, 0.64-0.92; P < 0.01). A rural background increased preferences for rural location (OR, 0.18; 95% CI, 0.15-0.22; P < 0.001) and in-need specialties (OR, 1.28; 95% CI, 1.04-1.57; P < 0.05), and being older on entry to medical school also increased preferences for rural location (OR, 0.96; 95% CI, 0.95-0.98; P < 0.001) and in-need specialties (OR, 1.03; 95% CI, 1.01-1.04; P < 0.01). International FFP students were more likely to prefer urban practice (OR, 1.79; 95% CI, 1.19-2.72; P < 0.01). CONCLUSION: Domestic FFP graduates are less likely to prefer careers in rural locations and in lower-paid and in-need specialties, particularly general practice. Current workforce implications might be minor, but if fees for CSP students increase or more FFP places become available, potential impacts on workforce distribution will need to be considered.

Haemophilus influenzae oral vaccination for preventing acute exacerbations of chronic bronchitis and chronic obstructive pulmonary disease.

BACKGROUND: Chronic bronchitis and chronic obstructive pulmonary disease (COPD) are serious conditions in which patients are predisposed to viral and bacterial infections resulting in potentially fatal acute exacerbations. COPD is defined as a lung disease characterised by obstruction to lung airflow that interferes with normal breathing. Antibiotic therapy has not been particularly useful in eradicating bacteria such as non-typeable Haemophilus influenzae (NTHi) because they are naturally occurring flora of the upper respiratory tract in many people. However, they can cause opportunistic infection. An oral NTHi vaccine has been developed to protect against recurrent infective acute exacerbations in chronic bronchitis. OBJECTIVES: To assess the effectiveness of an oral, whole-cell, non-typeable H. influenzae (NTHi) vaccine in protecting against recurrent episodes of acute exacerbations of chronic bronchitis and COPD in adults. To assess the effectiveness of NTHi vaccine in reducing NTHi colonising the respiratory tract during recurrent episodes of acute exacerbations of COPD. SEARCH METHODS: We searched the following databases: CENTRAL (2014, Issue 6), MEDLINE (1946 to July week 3, 2014), EMBASE (1974 to July 2014), CINAHL (1981 to July 2014), LILACS (1982 to July 2014) and Web of Science (1955 to July 2014). We also searched trials registries and contacted authors of trials requesting unpublished data. SELECTION CRITERIA: We included randomised controlled trials comparing the effects of an oral monobacterial NTHi vaccine in adults with recurrent acute exacerbations of chronic bronchitis or COPD when there was overt matching of the vaccine and placebo groups on clinical grounds. The selection criteria considered populations aged less than 65 years and those older than 65 years. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial quality and extracted data from original records and publications for incidence and severity of bronchitis episodes and carriage rate of NTHi measured in the upper respiratory tract, as well as data relevant to other primary and secondary outcomes. MAIN RESULTS: We identified six placebo-controlled randomised controlled trials with a total of 557 participants. They investigated the efficacy of enteric-coated, killed preparations of H. influenzae in populations prone to recurrent acute exacerbations of chronic bronchitis or COPD. The vaccine preparation and immunisation regime in all trials consisted of at least three courses of formalin-killed H. influenzae in enteric-coated tablets taken at intervals (for example, days 0, 28 and 56). Each course generally consisted of two tablets taken after breakfast over three consecutive days. In all cases the placebo groups took enteric-coated tablets containing glucose. Risk of bias was moderate across the studies, namely due to the lack of information provided about methods and inadequate presentation of results.Meta-analysis of the oral NTHi vaccine showed a small, non-statistically significant reduction in the incidence of acute exacerbations of chronic bronchitis or COPD by 2.048% (risk ratio (RR) 0.97, 95% confidence interval (CI) 0.84 to 1.12, P value = 0.68). There was no significant difference in mortality rate between the vaccine and placebo groups (odds ratio (OR) 1.62, 95% CI 0.63 to 4.12, P value = 0.31).We were unable to meta-analyse the carriage levels of NTHi in participants as each trial reported this result using different units and tools of measurement. Four trials showed no significant difference in carriage levels, while two trials showed a significant decrease in carriage levels in the vaccinated group compared with placebo.Four trials assessed severity of exacerbations measured by requirement for antibiotics. Three of these trials were comparable and when meta-analysed showed a statistically significant 80% increase in antibiotic courses per person in the placebo group (RR 1.81, 95% CI 1.35 to 2.44, P value < 0.0001). There was no significant difference between the groups with regards to hospital admission rates (OR 0.96, 95% CI 0.13 to 7.04, P value = 0.97). Adverse events were reported in all six trials with a point estimate suggestive that they occurred more frequently in the vaccine group, however, this result was not statistically significant (RR 1.43, 95% CI 0.70 to 2.92, P value = 0.87). Quality of life was not meta-analysed but was reported in two trials, with results at six months showing an improvement in quality of life in the vaccinated group (scoring at least two points better than placebo). AUTHORS' CONCLUSIONS: Analyses demonstrate that NTHi oral vaccination of patients with recurrent exacerbations of chronic bronchitis or COPD does not yield a significant reduction in the number and severity of exacerbations. Evidence is mixed and the individual trials that show a significant benefit of the vaccine are too small to advocate widespread oral vaccination of people with COPD.

Screening for colorectal cancer and advanced colorectal neoplasia in kidney transplant recipients: cross sectional prevalence and diagnostic accuracy study of faecal immunochemical testing for haemoglobin and colonoscopy.

OBJECTIVE: To investigate whether screening kidney transplant recipients aged over 50 years for colorectal cancer with a faecal immunochemical test for haemoglobin might be justified, by determining the prevalence of advanced colorectal neoplasia and evaluating the diagnostic accuracy of faecal haemoglobin testing compared with colonoscopy in a population of kidney transplant recipients at otherwise average risk. DESIGN: Cross sectional prevalence and diagnostic accuracy study with index test of faecal haemoglobin and reference standard of colonoscopy. SETTING: Outpatient clinics in metropolitan and regional hospitals in South Australia. PARTICIPANTS: 229 kidney transplant recipients aged 50 years and over, who were at least 6 months (mean 9.0 (SD 8.4) years) post-transplant and otherwise at average risk of colorectal cancer, completed the study between June 2008 and October 2011. INTERVENTIONS: Faecal immunochemical testing (Enterix Insure) for human haemoglobin, followed by colonoscopy with histological evaluation of retrieved samples. MAIN OUTCOME MEASURES: Prevalence of advanced colorectal neoplasia, defined as an adenoma at least 10 mm in diameter, villous features, high grade dysplasia, or colorectal cancer; sensitivity, specificity, and predictive values of faecal haemoglobin testing for advanced neoplasia compared with colonoscopy. RESULTS: Advanced colorectal neoplasia was found in 29 (13%, 95% confidence interval 9% to 18%) participants, including 2% (n=4) with high grade dysplasia and 2% (n=5) with colorectal cancer. Faecal testing for haemoglobin was positive in 12% (n=28); sensitivity, specificity, and positive and negative predictive values for advanced neoplasia were 31.0% (15.3% to 50.8%), 90.5% (85.6% to 94.2%), 32.1% (15.9% to 52.4%), and 90.1% (85.1% to 93.8%). Colonoscopy was well tolerated, with no significant adverse outcomes. To identify one case of advanced neoplasia, 8 (6 to 12) colonoscopies were needed. CONCLUSIONS: Kidney transplant recipients aged over 50 years have a high prevalence of advanced colorectal neoplasia. Faecal haemoglobin screening for colorectal neoplasia has similar performance characteristics in transplant recipients to those reported in general population studies, with poor sensitivity but reasonable specificity. Surveillance colonoscopy might be a more appropriate approach in this population. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12608000154303.

The role of capsule endoscopy in suspected celiac disease patients with positive celiac serology.

BACKGROUND: Endomysial antibody (EMA) and tissue transglutaminase (tTG) antibody testing is used to screen subjects with suspected celiac disease. However, the traditional gold standard for the diagnosis of celiac disease is histopathology of the small bowel. As villous atrophy may be patchy, duodenal biopsies could potentially miss the abnormalities. Capsule endoscopy can obtain images of the whole small intestine and may be useful in the early diagnosis of celiac disease. AIMS: To evaluate suspected celiac disease patients who have positive celiac serology and normal duodenal histology and to determine, with capsule endoscopy, whether these patients have any endoscopic markers of celiac disease. METHODS: Twenty-two subjects with positive celiac serology (EMA or tTG) were prospectively evaluated. Eight of the subjects had normal duodenal histology and 14 had duodenal histology consistent with celiac disease. All subjects underwent capsule endoscopy. Endoscopic markers of villous atrophy such as loss of mucosal folds, scalloping, mosaic pattern, and visible vessels were assessed. RESULTS: Eight subjects with normal duodenal histology had normal capsule endoscopy findings. In the 14 subjects with duodenal histology that was consistent with celiac disease, 13 had celiac disease changes seen at capsule endoscopy. One subject with normal capsule endoscopy findings showed Marsh IIIc on duodenal histology. Using duodenal histology as the gold standard, capsule endoscopy had a sensitivity of 93%, specificity of 100%, PPV of 100%, and NPV of 89% in recognizing villous atrophy. CONCLUSIONS: Capsule endoscopy is useful in the detection of villous abnormalities in untreated celiac disease. Patients with positive celiac serology (EMA or tTG) and normal duodenal histology are unlikely to have capsule endoscopy markers of villous atrophy.

Morphometric evaluation of duodenal biopsies in celiac disease.

OBJECTIVES: The Marsh classification is a semiquantitative method for the diagnosis and monitoring of changes in duodenal biopsies in celiac disease. We have explored the possibility that quantitative changes in villous area and crypt length (morphometry) may provide better information on changes in duodenal morphology, particularly after the introduction of a gluten-free diet. METHODS: We measured villous height, apical and basal villous widths, and crypt length in 57 adults with celiac disease and 83 control subjects. Villous area was calculated as a trapezoid approximation. Serial changes in villous area and crypt length were determined at regular intervals for up to 4 years after the introduction of a gluten-free diet. Morphometric changes were also correlated with Marsh grade, self-reported adherence to a gluten-free diet, and changes in celiac serology. RESULTS: The gluten-free diet resulted in a progressive increase in villous area and a progressive decrease in crypt length. Morphometric improvement reached a plateau after 6-12 months with mean villous area attaining a value approximately half that of control subjects. Morphometric data were more sensitive than Marsh grade. Improvement in morphometric indices was significantly associated with the disappearance of anti-endomysial IgA antibody but not with dietary compliance. CONCLUSIONS: Morphometry is a sensitive way to document changes in duodenal biopsies in celiac disease. In adults treated with a gluten-free diet, it is uncommon for villous area to return to values observed in control subjects, but morphometric improvement is associated with the disappearance of anti-endomysial IgA antibody.

Capsule endoscopy: a valuable tool in the follow-up of people with celiac disease on a gluten-free diet.

OBJECTIVES: Traditional celiac disease guidelines recommend follow-up endoscopy and duodenal biopsies at 6-12 months after commencing a gluten-free diet (GFD). However, histology may remain abnormal even 1-2 years later. We evaluated the role of capsule endoscopy in patients with celiac disease after treatment with a GFD. METHODS: Twelve adult patients with newly diagnosed celiac disease were prospectively enrolled. All patients had baseline symptom assessment, celiac serology (tissue transglutaminase antibody, tTG), and capsule endoscopy. Twelve months after commencing a GFD, patients underwent repeat symptom assessment, celiac serology, upper gastrointestinal endoscopy, and capsule endoscopy. RESULTS: At baseline, capsule endoscopy detected endoscopic markers of villous atrophy in the duodenum and extending to a variable distance along the small intestine. On the basis of small bowel transit time, the mean±s.e.m. percentage of small intestine with villous atrophy was 18.2±3.7%. After 12 months on a GFD, repeat capsule endoscopy demonstrated mucosal healing from a distal to proximal direction, and the percentage of small intestine with villous atrophy was significantly reduced to 3.4±1.2% (P=0.0014) and this correlated with improvement in the symptom score (correlation 0.69, P=0.01). There was a significant improvement in symptom score (5.2±1.0 vs. 1.7±0.4, P=0.0012) and reduction in immunoglobulin A-tTG levels (81.5±10.6 vs. 17.5±8.2, P=0.0005). However, 42% of subjects demonstrated persistent villous abnormality as assessed by duodenal histology. CONCLUSIONS: After 12 months on a GFD, patients with celiac disease demonstrate an improvement in symptoms, celiac serology, and the extent of disease as measured by capsule endoscopy. Mucosal healing occurs in a distal to proximal direction. The extent of mucosal healing correlates with improvement in symptoms. Duodenal histology does not reflect the healing that has occurred more distally.

The future of endoscopy.

Extraordinary developments have occurred in the field of endoscopy over the past 40 years. The era that began with the fiberoptic endoscope (fiberscope) has now moved to the videoscope and, more recently, to the capsule endoscope. Videoendoscopy will remain the major form of endoscopy for the next 5-10 years but, thereafter, diagnostic procedures including colonoscopy will increasingly be performed by capsule endoscopy. This change will be largely driven by patient preference rather than superior results from capsule studies. Image analysis of capsule studies will be accelerated by software that highlights abnormal areas and, by 2025, capsule studies will be 'read' by computer. For the next decade, more complex therapeutic procedures will be performed by a new group of therapeutic endoscopists using advanced videoscopes. Several new therapeutic procedures will emerge but natural orifice transluminal approaches will need to compete with advances in laparoscopic techniques. It is also likely that health administrators faced with escalating medical costs will demand that new and more expensive procedures not only facilitate patient care but result in superior health outcomes.

Colonoscopy: Art or science?

The focus on colorectal neoplasia has led to an exponential increase in the use of colonoscopy in many countries. Although colonoscopy facilitates the diagnosis and treatment of colonic disease, there are public health issues that include access, training, diagnostic accuracy, complications and additions to health-care costs. Because of this, colonoscopists have a responsibility to ensure that the procedure is appropriate, safe and of high-quality. This article addresses the issue of variation in technical skills that is known to exist within the endoscopic community, even among individuals with similar experience. While some of this variation reflects innate manual dexterity, another aspect is variation in the adoption of technical manoeuvers that facilitate various aspects of the procedure including rates for cecal intubation. Although technical manoeuvers are difficult to evaluate in controlled trials, there is persuasive data that high cecal intubation rates can be achieved by minimizing inflation and looping in the sigmoid colon and by the appropriate use of positional changes and abdominal pressure. In difficult settings, there is also benefit from the use of non-standard endoscopes and various accessories including overtubes.