Keith R. Neal

Effect of salt and water balance on recovery of gastrointestinal function after elective colonic resection: a randomised controlled trial

BACKGROUND Low concentrations of albumin in serum and long gastric emptying times have been returned to normal in dogs by salt and water restriction, or a high protein intake. We aimed to determine the effect of salt and water balance on recovery of gastrointestinal function after elective colonic resection in human beings. METHODS We randomly allocated ten patients to receive postoperative intravenous fluids in accordance present hospital practice (> or = 3 L water and 154 mmol sodium per day) and ten to receive a restricted intake (< or = 2 L water and 77 mmol sodium per day). All patients had no disease other than colonic cancer. The primary endpoint was solid and liquid-phase gastric emptying time, measured by dual isotope radionuclide scintigraphy on the fourth postoperative day. Secondary endpoints included time to first bowel movement and length of postoperative hospital stay. Analysis was by intention to treat. FINDINGS Median solid and liquid phase gastric emptying times (T(50)) on the fourth postoperative day were significantly longer in the standard group than in the restricted group (175 vs 72.5 min, difference 56 [95% CI 12-132], p=0.028; and 110 vs 73.5 min, 52 [9-95], p=0.017, respectively). Median passage of flatus was 1 day later (4 vs 3 days, 2 [1-2], p=0.001); median passage of stool 2.5 days later (6.5 vs 4 days, 3 [2-4], p=0.001); and median postoperative hospital stay 3 days longer (9 vs 6 days, 3 [1-8], p=0.001) in the standard group than in the restricted group. One patient in the restricted group developed hypokalaemia, whereas seven patients in the standard group had side-effects or complications (p=0.01). INTERPRETATION Positive salt and water balance sufficient to cause a 3 kg weight gain after surgery delays return of gastrointestinal function and prolongs hospital stay in patients undergoing elective colonic resection.

The enhanced recovery after surgery (ERAS) pathway for patients undergoing major elective open colorectal surgery: a meta-analysis of randomized controlled trials.

BACKGROUND & AIMS The aim of the Enhanced Recovery After Surgery (ERAS) pathway is to attenuate the stress response to surgery and enable rapid recovery. The objective of this meta-analysis was to study the differences in outcomes in patients undergoing major elective open colorectal surgery within an ERAS pathway and those treated with conventional perioperative care. METHODS Medline, Embase and Cochrane database searches were performed for relevant studies published between January 1966 and November 2009. All randomized controlled trials comparing ERAS with conventional perioperative care were selected. The outcome measures studied were length of hospital stay, complication rates, readmission rates and mortality. RESULTS Six randomized controlled trials with 452 patients were included. The number of individual ERAS elements used ranged from 4 to 12, with a mean of 9. The length of hospital stay [weighted mean difference (95% confidence interval): -2.55 (-3.24, -1.85)] and complication rates [relative risk (95% confidence interval): 0.53 (0.44, 0.64)] were significantly reduced in the enhanced recovery group. There was no statistically significant difference in readmission and mortality rates. CONCLUSION ERAS pathways appear to reduce the length of stay and complication rates after major elective open colorectal surgery without compromising patient safety.

Prevalence of gastrointestinal symptoms six months after bacterial gastroenteritis and risk factors for development of the irritable bowel syndrome: postal survey of patients

Abstract Objective: To measure the prevalence of gastrointestinal symptoms six months after bacterial gastroenteritis and determine risk factors and associations with postdysenteric symptoms. Design: Postal questionnaire. Setting: Nottingham Health Authority. Subjects: 544 people with microbiologically confirmed bacterial gastroenteritis between July 1994 and December 1994. Main outcome measures: Prevalence of gastrointestinal symptoms and relative risks for development of the irritable bowel syndrome and self reported altered bowel habit. Results: A quarter of subjects reported persistence of altered bowel habit six months after an episode of infective gastroenteritis. Increasing duration of diarrhoea, younger age, and female sex increased this risk, whereas vomiting as part of the illness reduced the risk. One in 14 developed the irritable bowel syndrome with an increased risk seen in women (relative risk 3.4; 95% confidence interval 1.2 to 9.8) and with duration of diarrhoea (6.5; 1.3 to 34 for 15-21 days). Conclusions: Persistence of bowel symptoms commonly occurs after bacterial gastroenteritis and is responsible for considerable morbidity and health care costs.

Impact of meningococcal serogroup C conjugate vaccines on carriage and herd immunity

BACKGROUND In 1999, meningococcal serogroup C conjugate (MCC) vaccines were introduced in the United Kingdom for those under 19 years of age. The impact of this intervention on asymptomatic carriage of meningococci was investigated to establish whether serogroup replacement or protection by herd immunity occurred. METHODS Multicenter surveys of carriage were conducted during vaccine introduction and on 2 successive years, resulting in a total of 48,309 samples, from which 8599 meningococci were isolated and characterized by genotyping and phenotyping. RESULTS A reduction in serogroup C carriage (rate ratio, 0.19) was observed that lasted at least 2 years with no evidence of serogroup replacement. Vaccine efficacy against carriage was 75%, and vaccination had a disproportionate impact on the carriage of sequence type (ST)-11 complex serogroup C meningococci that (rate ratio, 0.06); these meningococci also exhibited high rates of capsule expression. CONCLUSIONS The impact of vaccination with MCC vaccine on the prevalence of carriage of group C meningococci was consistent with herd immunity. The high impact on the carriage of ST-11 complex serogroup C could be attributed to high levels of capsule expression. High vaccine efficacy against disease in young children, who were not protected long-term by the schedule initially used, is attributed to the high vaccine efficacy against carriage in older age groups.

Prognosis in post-infective irritable bowel syndrome: a six year follow up study

Background: Irritable bowel syndrome developing following infective gastroenteritis accounts for approximately 1 in 10 of unselected IBS patients. Aims: To define the long term natural history of post-infective IBS (PI-IBS). Methods: A total of 436 individuals, who had previously responded to a questionnaire on their bowel habits following an acute episode of gastroenteritis, were sent a questionnaire about their current bowel habits and physical and mental health six years after their initial illness. Results: Complete data on original bowel habit, episodes of gastroenteritis, mental health history, and subsequent bowel habit at six years were obtained in 192 individuals. Of these, there were 14 cases of “post-infective IBS” (PI-IBS) and 13 who had IBS prior to infection (previous IBS). Over the six year follow up period there were 20 “new non-infective IBS cases” (new IBS). The strongest risk factor for developing any type of IBS was female sex (relative risk 2.2, p<0.05). Compared with new IBS, those with PI-IBS had significantly more days with loose stools (p<0.05) but a similar number of days with pain, urgency, and bloating. Six of 14 (43%) PI-IBS and four of 13 (31%) previous IBS patients recovered by six years (NS). Of 27 IBS patients followed for six years, only 1/8 with a history of anxiety or depression recovered compared with 9/19 without such a history (p=0.19). Conclusion: PI-IBS differs from non-infective IBS by having more diarrhoeal features. Less than half of both PI-IBS and non-infective IBS cases recover over six years. A history of anxiety and depression severe enough to warrant treatment may impair recovery but larger numbers are needed to prove this.

Stapled hemorrhoidopexy compared with conventional hemorrhoidectomy: Systematic review of randomized, controlled trials

PURPOSEThis study was designed to determine whether conventional hemorrhoidectomy or stapled hemorrhoidopexy is superior for the management of hemorrhoids.METHODSA systematic review of all randomized trials comparing conventional hemorrhoidectomy with stapled hemorrhoidopexy was performed. MEDLINE, EMBASE, and Cochrane Library databases were searched using the terms “hemorrhoid*” or “haemorrhoid*” and “stapl*.” A list of clinical outcomes was extracted. Meta-analysis was calculated if possible.RESULTSFifteen trials recruiting 1,077 patients were included. Follow-up ranged from 6 weeks to 37 months. Qualitative analysis showed that stapled hemorrhoidopexy is less painful compared with hemorrhoidectomy. Stapled hemorrhoidopexy has a shorter inpatient stay (weighted mean difference, –1.02 days; 95 percent confidence interval, –1.47 to –0.57; P = 0.0001), operative time (weighted mean difference, –12.82 minutes; 95 percent confidence interval, –22.61 to –3.04; P = 0.01), and return to normal activity (standardized mean difference, –4.03 days; 95 percent confidence interval, –6.95 to –1.10; P = 0.007). Studies in a day-case setting do not prove that stapled hemorrhoidopexy is more feasible than conventional hemorrhoidectomy. Stapled hemorrhoidopexy has a higher recurrence rate (odds ratio, 3.64; 95 percent confidence interval, 1.40–9.47; P = 0.008) at a minimum follow-up of six months.CONCLUSIONSAlthough stapled hemorrhoidopexy is widely used, the data available on long-term outcomes is limited. The variability in case selection and reported end points are difficulties in interpreting results. Stapled hemorrhoidopexy has unique potential complications and is a less effective cure compared with hemorrhoidectomy. With this understanding, it may be offered to patients seeking a less painful alternative to conventional surgery. Hemorrhoidectomy remains the “gold standard” of treatment.

Safety and efficacy of antibiotics compared with appendicectomy for treatment of uncomplicated acute appendicitis: meta-analysis of randomised controlled trials

Objective To compare the safety and efficacy of antibiotic treatment versus appendicectomy for the primary treatment of uncomplicated acute appendicitis. Design Meta-analysis of randomised controlled trials. Population Randomised controlled trials of adult patients presenting with uncomplicated acute appendicitis, diagnosed by haematological and radiological investigations. Interventions Antibiotic treatment versus appendicectomy. Outcome measures The primary outcome measure was complications. The secondary outcome measures were efficacy of treatment, length of stay, and incidence of complicated appendicitis and readmissions. Results Four randomised controlled trials with a total of 900 patients (470 antibiotic treatment, 430 appendicectomy) met the inclusion criteria. Antibiotic treatment was associated with a 63% (277/438) success rate at one year. Meta-analysis of complications showed a relative risk reduction of 31% for antibiotic treatment compared with appendicectomy (risk ratio (Mantel-Haenszel, fixed) 0.69 (95% confidence interval 0.54 to 0.89); I2=0%; P=0.004). A secondary analysis, excluding the study with crossover of patients between the two interventions after randomisation, showed a significant relative risk reduction of 39% for antibiotic therapy (risk ratio 0.61 (0.40 to 0.92); I2=0%; P=0.02). Of the 65 (20%) patients who had appendicectomy after readmission, nine had perforated appendicitis and four had gangrenous appendicitis. No significant differences were seen for treatment efficacy, length of stay, or risk of developing complicated appendicitis. Conclusion Antibiotics are both effective and safe as primary treatment for patients with uncomplicated acute appendicitis. Initial antibiotic treatment merits consideration as a primary treatment option for early uncomplicated appendicitis.

Randomized, double-blind, placebo-controlled trial of prednisolone in post-infectious irritable bowel syndrome

Background : Post‐infectious irritable bowel syndrome is associated with increased serotonin‐containing enterochromaffin cells and lymphocytes in rectal biopsies. Animal studies have suggested that steroids reduce the lymphocyte response and suppress some of the post‐infectious changes in neuromuscular function.

Social Behavior and Meningococcal Carriage in British Teenagers

Understanding predisposing factors for meningococcal carriage may identify targets for public health interventions. Before mass vaccination with meningococcal group C conjugate vaccine began in autumn 1999, we took pharyngeal swabs from ≈14,000 UK teenagers and collected information on potential risk factors. Neisseria meningitidis was cultured from 2,319 (16.7%) of 13,919 swabs. In multivariable analysis, attendance at pubs/clubs, intimate kissing, and cigarette smoking were each independently and strongly associated with increased risk for meningococcal carriage (p<0.001). Carriage in those with none of these risk factors was 7.8%, compared to 32.8% in those with all 3. Passive smoking was also linked to higher risk for carriage, but age, sex, social deprivation, home crowding, or school characteristics had little or no effect. Social behavior, rather than age or sex, can explain the higher frequency of meningococcal carriage among teenagers. A ban on smoking in public places may reduce risk for transmission.

Effect of a quadrivalent meningococcal ACWY glycoconjugate or a serogroup B meningococcal vaccine on meningococcal carriage: an observer-blind, phase 3 randomised clinical trial

BACKGROUND Meningococcal conjugate vaccines protect individuals directly, but can also confer herd protection by interrupting carriage transmission. We assessed the effects of meningococcal quadrivalent glycoconjugate (MenACWY-CRM) or serogroup B (4CMenB) vaccination on meningococcal carriage rates in 18-24-year-olds. METHODS In this phase 3, observer-blind, randomised controlled trial, university students aged 18-24 years from ten sites in England were randomly assigned (1:1:1, block size of three) to receive two doses 1 month apart of Japanese Encephalitis vaccine (controls), 4CMenB, or one dose of MenACWY-CRM then placebo. Participants were randomised with a validated computer-generated random allocation list. Participants and outcome-assessors were masked to the treatment group. Meningococci were isolated from oropharyngeal swabs collected before vaccination and at five scheduled intervals over 1 year. Primary outcomes were cross-sectional carriage 1 month after each vaccine course. Secondary outcomes included comparisons of carriage at any timepoint after primary analysis until study termination. Reactogenicity and adverse events were monitored throughout the study. Analysis was done on the modified intention-to-treat population, which included all enrolled participants who received a study vaccination and provided at least one assessable swab after baseline. This trial is registered with ClinicalTrials.gov, registration number NCT01214850. FINDINGS Between Sept 21 and Dec 21, 2010, 2954 participants were randomly assigned (987 assigned to control [984 analysed], 979 assigned to 4CMenB [974 analysed], 988 assigned to MenACWY-CRM [983 analysed]); 33% of the 4CMenB group, 34% of the MenACWY-CRM group, and 31% of the control group were positive for meningococcal carriage at study entry. By 1 month, there was no significant difference in carriage between controls and 4CMenB (odds ratio 1·2, 95% CI 0·8-1·7) or MenACWY-CRM (0·9, [0·6-1·3]) groups. From 3 months after dose two, 4CMenB vaccination resulted in significantly lower carriage of any meningococcal strain (18·2% [95% CI 3·4-30·8] carriage reduction), capsular groups BCWY (26·6% [10·5-39·9] carriage reduction), capsular groups CWY (29·6% [8·1-46·0] carriage reduction), and serogroups CWY (28·5% [2·8-47·5] carriage reduction) compared with control vaccination. Significantly lower carriage rates were also noted in the MenACWY-CRM group compared with controls: 39·0% (95% CI 17·3-55·0) carriage reduction for serogroup Y and 36·2% (15·6-51·7) carriage reduction for serogroup CWY. Study vaccines were generally well tolerated, with increased rates of transient local injection pain and myalgia in the 4CMenB group. No safety concerns were identified. INTERPRETATION Although we detected no significant difference between groups at 1 month after vaccine course, MenACWY-CRM and 4CMenB vaccines reduced meningococcal carriage rates during 12 months after vaccination and therefore might affect transmission when widely implemented. FUNDING Novartis Vaccines.