Stepped-wedge randomized controlled trial of laparoscopic ventral mesh rectopexy in adults with chronic constipation.

BACKGROUND: The effectiveness of laparoscopic ventral mesh rectopexy (LVMR) in patients with defecatory disorders secondary to internal rectal prolapse is poorly evidenced. A UK-based multicenter randomized controlled trial was designed to determine the clinical efficacy of LVMR compared to controls at medium-term follow-up. METHODS: The randomized controlled trial was conducted from March 1, 2015 TO January 31, 2019. A stepped-wedge RCT design permitted observer-masked data comparisons between patients awaiting LVMR (controls) with those who had undergone surgery. Adult participants with radiologically confirmed IRP refractory to conservative treatment were randomized to three arms with different delays before surgery. Efficacy outcome data were collected at equally stepped time points (12, 24, 36, 48, 60, and 72 weeks). Clinical efficacy of LVMR compared to controls was defined as ≥ 1.0-point reduction in Patient Assessment of Constipation-Quality of Life and/or Symptoms (PAC-QOL and/or PAC-SYM) scores at 24 weeks. Secondary outcome measures included 14-day diary data, the Generalized Anxiety Disorder scale (GAD-7), the Patient Health Questionnaire-9 (PHQ-9), St Marks incontinence score, the Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ-12), the chronic constipation Behavioral Response to Illness Questionnaire (CC-BRQ), and the Brief Illness Perception Questionnaire (BIPQ). RESULTS: Of a calculated sample size of 114, only 28 patients (100% female) were randomized from 6 institutions (due mainly to national pause on mesh-related surgery). Nine were assigned to the T0 arm, 10 to T12, and 9 to T24. There were no substantial differences in baseline characteristics between the three arms. Compared to baseline, significant reduction (improvement) in PAC-QOL and PAC-SYM scores were observed at 24 weeks post-surgery (- 1.09 [95% CI - 1.76, - 0.41], p = 0.0019, and - 0.92 [- 1.52, - 0.32], p = 0.0029, respectively) in the 19 patients available for analysis (9 were excluded for dropout [n = 2] or missing primary outcome [n = 7]). There was a clinically significant long-term reduction in PAC-QOL scores (- 1.38 [- 2.94, 0.19], p = 0.0840 at 72 weeks). Statistically significant improvements in PAC-SYM scores persisted to 72 weeks (- 1.51 [- 2.87, - 0.16], p = 0.0289). Compared to baseline, no differences were found in secondary outcomes, except for significant improvements at 24 and 48 weeks on CC-BRQ avoidance behavior (- 14.3 [95% CI - 23.3, - 5.4], and - 0.92 [- 1.52, - 0.32], respectively), CC-BRQ safety behavior (- 13.7 [95% CI - 20.5, - 7.0], and - 13.0 [- 19.8, - 6.1], respectively), and BIPQ negative perceptions (- 16.3 [95% CI - 23.5, - 9.0], and - 10.5 [- 17.9, - 3.2], respectively). CONCLUSIONS: With the caveat of under-powering due to poor recruitment, the study presents the first randomized trial evidence of short-term benefit of LVMR for internal rectal prolapse. TRIAL REGISTRATION: ISRCTN Registry (ISRCTN11747152).

Development of a theory-based intervention to increase cognitively able frail elders' engagement with advance care planning using the behaviour change wheel.

BACKGROUND: Advance care planning (ACP) conversations support people to think about, discuss and document their beliefs, values and preferences regarding future care. This process means that should the person loose capacity in the future, care can be provided, consistent with their personal values and beliefs. The ACP process is particularly relevant for older people living with frailty (frail elders) as they are vulnerable to sudden deterioration. However, ACP is rarely undertaken by frail elders. The aim of this study was to develop an intervention to increase multidisciplinary health and social care professionals' (H&SCPs) engagement of cognitively able, domestic-dwelling frail elders with ACP. METHODS: Intervention development was guided by the Medical Research Council framework for complex interventions and the Behaviour Change Wheel. Multiple methods were used to understand ACP barriers and enablers: a systematic integrative review, a survey (n = 73 H&SCPs), and semi-structured interviews (n = 10 frail elders, n = 8 family members). A conceptual model, developed from the integrative review, underpinned data collection for the survey and interviews. Synthesis of this data, including patient and public involvement, was then used to identify H&SCPs behaviours that needed to change for ACP to be implemented and decide content and implementation for the intervention. RESULTS: Following the Behaviour Change Wheel system, and based on the findings of the review, survey and interviews, the prototype intervention, Conversations on Living and Dying (CLaD), was developed. The CLaD prototype consisted of one 3.5-hour educational skills session for H&SCPs supported by a toolkit. Content focussed on the relevance of ACP for frail elders, experience of ACP by frail elders, and strategies H&SCPs could adopt to encourage frail elders' engagement with ACP. Strategies include recognising the importance of relationships and living well now, preparing frail elders for ACP conversations and starting ACP early. Participants who took part in initial prototype refinement reported that the intervention helped them think differently about ACP and encouraged them to engage with frail elders. CONCLUSIONS: The use of behavioural theory enabled the development of CLaD, an evidence-based, theory-driven, person-centred intervention to support ACP engagement with frail elders. While feasibility testing is required, initial prototype refinement demonstrated that H&SCPs found the intervention to be acceptable, engaging, and clinically valuable in their practice with frail elders and their families.

Nanocarried antioxidants in freezing extenders for boar spermatozoa.

Post-thawing cryoinjuries in boar spermatozoa due to oxidative stress may be reduced by adding nanoencapsulated antioxidants to freezing extenders. This study evaluated post-thawing kinetics, structural and biochemical functions of boar spermatozoa frozen with extenders including resveratrol and vitamin E loaded into polymeric nanocapsules. Resveratrol was added at 0 (control), 5, 10, 20, 40 and 80 µg/ml, whereas Vitamin E was added at 0 (control), 50, 100, 200 and 400 µg/ml. Both antioxidants were tested in free and nanoencapsulated presentations. In contact with empty nanocapsules, some sperm kinetics parameters were impaired compared to the control (p < .05), whereas lipoperoxidation declined (p < .05). With inclusion of 40 µg/ml nanoencapsulated resveratrol, some sperm kinetics parameters were improved (p < .01), but sperm motility, structural and biochemical functions did not differ from the control (p > .05). No improvement in sperm quality occurred with inclusion of vitamin E, although sperm kinetics with 400 µg/ml nanoencapsulated vitamin E was reduced compared to the control (p < .01). Inclusion of 40 µg/ml nanoencapsulated resveratrol benefitted boar sperm kinetics after thawing, but no improvement resulted from inclusion of vitamin E.

Routine testing of close contacts of confirmed COVID-19 cases - National COVID-19 Contact Management Programme, Ireland, May to August 2020.

OBJECTIVES: The objective of this study was to inform public health practitioners who are designing, adapting and implementing testing and tracing strategies for Coronavirus disease (COVID-19) control. STUDY DESIGN: The study design is monitoring and evaluation of a national public health protection programme. METHODS: All close contacts of laboratory-confirmed cases of COVID-19 identified between the 19th May and 2nd August were included; secondary attack rates and numbers needed to test were estimated. RESULTS: Four thousand five hundred eighty six of 7272 (63%) close contacts of cases were tested with at least one test. The secondary attack rate in close contacts who were tested was 7% (95% Confidence Interval [CI]: 6.3 - 7.8%). At the 'day 0' test, 14.6% (95% CI: 11.6-17.6%) of symptomatic close contacts tested positive compared with 5.2% (95% CI: 4.4-5.9%) of asymptomatic close contacts. CONCLUSIONS: The application of additional symptom-based criteria for testing in this high-incidence population (close contacts) is of limited utility because of the low negative predictive value of absence of symptoms.

People and Plants in Nunatsiavut (Labrador, Canada): Examining Plants as a Foundational Aspect of Culture in the Subarctic.

This paper emphasizes the cultural value of plants in Nunatsiavut (Labrador, Canada), a self-governing Inuit region in the Subarctic. Via interviews with community members, we describe the links between plant usage and culture to understand the direct ways that plants are utilized for food, construction, gardening, and medicine, and to then link these uses to deeper cultural significance among three communities in Nunatsiavut (Hopedale, Postville, and Rigolet). Many plants were common amongst communities with a total of 66 taxa identified. About 75% of taxa were reported in at least two communities, corresponding to 95% of all responses. Edible plants were the most common reported usage, with emphasis on berry-producing taxa such as blueberry shrubs. Our study shows that a diversity of plants (i) support cultural activities; (ii) act as markers for historical events; (iii) highlight intergenerational exchange and valuing of plant knowledge; (iv) express the deep awareness that people have for their local environment; and (v) a medium for the expression of traditional values. The similarities in the plant responses among the communities suggest a shared body of plant knowledge. Our study supports the great cultural importance of plants in northern communities. Supplementary Information: The online version contains supplementary material available at 10.1007/s12231-021-09530-7.

Depressive symptoms in inflammatory bowel disease: an extraintestinal manifestation of inflammation?

Depressive symptoms are reported by more than 20% of people with inflammatory bowel disease (IBD), while sleep difficulties and fatigue are even more common. Co-morbid depressive symptoms predict a poor IBD course, including increased risk of relapse and surgery, which is inconsistently improved by psychological treatments. Rather than being distinct systems, there is compelling evidence for bidirectional communication between gut and brain, driven by neural, metabolic, endocrine and inflammatory mediators. An emerging concept is that depressive symptoms may be mechanistically linked to excess inflammation and dysregulation of the gut-brain axis. Given the close link between the intestinal microbiota and host immune responses, patients prone to shifts in their intestinal microbiome, including smokers, those with poor diet and early life stress, may be exposed to exaggerated immune responses. Excess inflammation is associated with brain changes (depressive symptoms, fatigue, sleep difficulties) and worsening gastrointestinal symptoms, which are exacerbated by psychological distress. Equally, treatments both for depressive symptoms and IBD provide opportunities to break this cycle by reducing the causes and effects of inflammation. As well as addressing potential risk factors such as smoking and diet, treatments to alter the microbiome may reduce depressive symptoms. Observational evidence suggests that anti-inflammatory treatments for IBD may improve co-morbid depressive symptoms correlating with reduction in inflammation. With a growing range of treatments targeting inflammation centrally, peripherally and in the gut, IBD provides a unique model to understand the interplay between brain and gut in the pathogenesis of depressive symptoms, both in IBD and in the whole population.

The Impact of System Factors on Quality and Safety in Arterial Surgery: A Systematic Review.

OBJECTIVE: A systems approach to patient safety proposes that a wide range of factors contribute to surgical outcome, yet the impact of team, work environment, and organisational factors, is not fully understood in arterial surgery. The aim of this systematic review is to summarize and discuss what is already known about the impact of system factors on quality and safety in arterial surgery. DATA SOURCES: A systematic review of original research papers in English using MEDLINE, Embase, PsycINFO, and Cochrane databases, was performed according to PRISMA guidelines. REVIEW METHODS: Independent reviewers selected papers according to strict inclusion and exclusion criteria, and using predefined data fields, extracted relevant data on team, work environment, and organisational factors, and measures of quality and/or safety, in arterial procedures. RESULTS: Twelve papers met the selection criteria. Study endpoints were not consistent between papers, and most failed to report their clinical significance. A variety of tools were used to measure team skills in five papers; only one paper measured the relationship between team factors and patient outcomes. Two papers reported that equipment failures were common and had a significant impact on operating room efficiency. The influence of hospital characteristics on failure-to-rescue rates was tested in one large study, although their conclusions were limited to the American Medicare population. Five papers implemented changes in the patient pathway, but most studies failed to account for potential confounding variables. CONCLUSIONS: A small number of heterogenous studies have evaluated the relationship between system factors and quality or safety in arterial surgery. There is some evidence of an association between system factors and patient outcomes, but there is more work to be done to fully understand this relationship. Future research would benefit from consistency in definitions, the use of validated assessment tools, measurement of clinically relevant endpoints, and adherence to national reporting guidelines.

Multicentre observational study of surgical system failures in aortic procedures and their effect on patient outcomes.

BACKGROUND: Vascular surgical care has changed dramatically in recent years with little knowledge of the impact of system failures on patient safety. The primary aim of this multicentre observational study was to define the landscape of surgical system failures, errors and inefficiency (collectively termed failures) in aortic surgery. Secondary aims were to investigate determinants of these failures and their relationship with patient outcomes. METHODS: Twenty vascular teams at ten English hospitals trained in structured self-reporting of intraoperative failures (phase I). Failures occurring in open and endovascular aortic procedures were reported in phase II. Failure details (category, delay, consequence), demographic information (patient, procedure, team experience) and outcomes were reported. RESULTS: There were strong correlations between the trainer and teams for the number and type of failures recorded during 88 procedures in phase I. In 185 aortic procedures, teams reported a median of 3 (i.q.r. 2-6) failures per procedure. Most frequent failures related to equipment (unavailability, failure, configuration, desterilization). Most major failures related to communication. Fourteen failures directly harmed 12 patients. Significant predictors of an increased failure rate were: endovascular compared with open repair (incidence rate ratio (IRR) for open repair 0·71, 95 per cent c.i. 0·57 to 0·88; P = 0·002), thoracic aneurysms compared with other aortic pathologies (IRR 2·07, 1·39 to 3·08; P < 0·001) and unfamiliarity with equipment (IRR 1·52, 1·20 to 1·91; P < 0·001). The major failure total was associated with reoperation (P = 0·011), major complications (P = 0·029) and death (P = 0·027). CONCLUSION: Failure in aortic procedures is frequently caused by issues with team-working and equipment, and is associated with patient harm. Multidisciplinary team training, effective use of technology and new-device accreditation may improve patient outcomes.

Systematic review of tibial nerve stimulation to treat faecal incontinence.

BACKGROUND: Two forms of tibial nerve stimulation are used to treat faecal incontinence (FI): percutaneous (PTNS) and transcutaneous (TTNS) tibial nerve stimulation. This article critically appraises the literature on both procedures. METHODS: A systematic review was performed adhering to the PRISMA framework. A comprehensive literature search was conducted, with systematic methodological quality assessment and data extraction. Summary measures for individual outcome variables are reported. RESULTS: Twelve articles met eligibility criteria; six related to PTNS, five to TTNS, and one to both procedures. These included ten case series and two randomized clinical trials (RCTs). Case series were evaluated using the National Institute for Health and Care Excellence quality assessment for case series, scoring 3-6 of 8. RCTs were evaluated using the Jadad score, scoring 4 of a possible 5 marks, and the Cochrane Collaboration bias assessment tool. From one RCT and case series reports, the success rate of PTNS, based on the proportion of patients who achieved a reduction in weekly FI episodes of at least 50 per cent, was 63-82 per cent, and that of TTNS was 0-45 per cent. In an RCT of TTNS versus sham, no patient had a reduction in weekly FI episodes of 50 per cent or more, whereas in an RCT of PTNS versus TTNS versus sham, 82 per cent of patients undergoing PTNS, 45 per cent of those having TTNS, and 13 per cent of patients in the sham group had treatment success. CONCLUSION: PTNS and TTNS result in significant improvements in some outcome measures; however, TTNS was not superior to sham stimulation in a large, adequately powered, RCT. As no adequate RCT of PTNS versus sham has been conducted, conclusions cannot be drawn regarding this treatment.

A pilot study of transcutaneous sacral nerve stimulation for faecal incontinence.

AIM: Although effective in faecal incontinence (FI), sacral nerve stimulation (SNS) is expensive and requires two procedures. It carries a small risk of infection and electrode migration. Transcutaneous SNS is noninvasive and cheap. Two small studies have reported the results when applied to segments S3 but there is no information on its effectiveness when applied to the whole sacral area. METHOD: A pilot study was carried out of self-administered transcutaneous SNS given over a 4-week period for 12 h a day. A 2-week bowel diary was kept for the final 2 weeks and compared with baseline. Patients were assessed using the St Mark's Incontinence Score, a visual analogue scale assessing satisfaction with bowel habit, the Rockwood FI Quality of Life (QOL) score and SF-36 QOL score. RESULTS: Of the 10 patients recruited, two achieved complete continence. There was a statistically significant reduction in the median (interquartile range) frequency of incontinent episodes per week from 9.5 (7.5) to 3 (7.38) (P = 0.03), and in the median frequency of defaecation per week from 25.5 (19.5) to 14.5 (14.9) (P = 0.007). There was a statistically significant improvement in the median ability to defer defaecation from 1 (1.25) to 4.5 (4.5) min (P = 0.02). There was also a statistically significant improvement in the St Marks Incontinence Score from 20 (5.25) to 14.5 (8.0) (P = 0.01) and in the bowel habit satisfaction visual analogue scale from 8.5 (20) to 45 (33) (P = 0.008). There was no change in the Rockwood FI QOL or SF-36 QOL scores. No complications were reported. CONCLUSION: Transcutaneous SNS appears to be an effective and safe treatment for FI. Larger controlled studies are needed to explore this further.

Lymphatic muscle cells are the innate pacemaker cells regulating mouse lymphatic collecting vessel contractions.

Collecting lymphatic vessels (cLVs) exhibit spontaneous contractions with a pressure-dependent frequency, but the identity of the lymphatic pacemaker cell is still debated. By analogy to pacemakers in the GI and lower urinary tracts, proposed cLV pacemaker cells include interstitial cells of Cajal like cells (ICLC), pericytes, as well as the lymphatic muscle (LMCs) cells themselves. Here we tested the extent to which these cell types are invested into the mouse cLV wall and if any cell type exhibited morphological and functional processes characteristic of pacemaker cells: a contiguous network; spontaneous Ca2+ transients; and depolarization-induced propagated contractions. We employed inducible Cre (iCre) mouse models routinely used to target these specific cell populations including: c-kitCreERT2 to target ICLC; PdgfrßCreERT2 to target pericytes; PdgfrαCreER™ to target CD34+ adventitial fibroblast-like cells or ICLC; and Myh11CreERT2 to target LMCs. These specific inducible Cre lines were crossed to the fluorescent reporter ROSA26mT/mG, the genetically encoded Ca2+ sensor GCaMP6f, and the light-activated cation channel rhodopsin2 (ChR2). c-KitCreERT2 labeled both a sparse population of LECs and round adventitial cells that responded to the mast cell activator compound 48-80. PdgfrßCreERT2 drove recombination in both adventitial cells and LMCs, limiting its power to discriminate a pericyte specific population. PdgfrαCreER™ labeled a large population of interconnected, oak leaf-shaped cells primarily along the adventitial surface of the vessel. Titrated induction of the smooth muscle-specific Myh11CreERT2 revealed a LMC population with heterogeneous morphology. Only LMCs consistently, but heterogeneously, displayed spontaneous Ca2+ events during the diastolic period of the contraction cycle, and whose frequency was modulated in a pressure-dependent manner. Optogenetic depolarization through the expression of ChR2 by Myh11CreERT2, but not PdgfrαCreER™ or c-KitCreERT2, resulted in a propagated contraction. These findings support the conclusion that LMCs, or a subset of LMCs, are responsible for mouse cLV pacemaking.

Percutaneous tibial nerve stimulation for slow transit constipation: a pilot study.

AIM: Chronic constipation is a problem with debilitating effects on patients' quality of life. This study aimed to evaluate the effectiveness of percutaneous tibial nerve stimulation in patients with slow transit constipation. METHOD: Eighteen patients (17 women, median age 47 years, range 21-74) with slow transit constipation previously failing maximal biofeedback therapy participated in the study. Patients had 12 sessions of 30 minutes of percutaneous tibial nerve stimulation. Wexner constipation score (0-30, 30 being the worst) was the primary outcome, colonic transit time, bowel diary and Patient Assessment of Constipation Quality of Life (PAC-QOL) were evaluated pre- and post-treatment. RESULTS: Wexner constipation score improved significantly with treatment (median 18 pre-treatment, range 10-24, to median 14 post-treatment, range 7-22; P = 0.003). The PAC-QOL also showed significant improvement (median 2.31, range 1.36-3.61, to median 1.43, range 0.39-3.78; P = 0.008). Stool frequency increased (P = 0.048) and the use of laxatives decreased (P = 0.025). There was no change in colonic transit time (P = 0.45). CONCLUSION: Percutaneous tibial nerve stimulation has potential as an affordable and minimally invasive treatment for slow transit constipation.

The impact of stoma for bowel management after spinal cord injury.

STUDY DESIGN: Multi-centre, retrospective self-report postal survey. OBJECTIVES: To characterise spinal cord injured (SCI) individuals with a stoma, their stoma management and outcomes, to identify sources of information and support for decision making and to explore the impact of a stoma on life satisfaction. SETTING: Five UK spinal cord injury centres. METHODS: A study-specific questionnaire accompanied by self-concept, life satisfaction and mood measures, and three simple rating scales for satisfaction, impact and restriction on life were sent to all known ostomates at five participating centres. RESULTS: Respondents were 92 individuals, mean age 56 years, mean duration of injury 26 years, 91% with colostomy. Multiple sources of information were utilised in deciding on surgery; discussion with other SCI ostomates was important. Duration of bowel care, faecal incontinence, bowel-related autonomic dysreflexia, dietary manipulation and laxative use were all significantly reduced following surgery. Rectal mucous discharge was the most common and bothersome post-stoma problem. Satisfaction with stoma was high; provision of sufficient information preoperatively was important, those with ileostomy were more dependent and less satisfied. Life satisfaction and physical self-concept were both lower in this sample than in previously reported samples of SCI individuals without reported bowel difficulties or stoma. CONCLUSION: The findings of this study of self-selected respondents with a stoma for bowel management after SCI emphasised the benefits of stoma in selected individuals and the importance of timely intervention, the complexity of the associated decision-making and of preoperative counselling. The impact of bowel dysfunction on physical self-concept warrants investigation.

Apolipoprotein A5-1131T>C polymorphism, but not APOE genotypes, increases susceptibility for dyslipidemia in children and adolescents.

Apolipoprotein A5 (APOA5) and apolipoprotein E (APOE) play important roles in the metabolism of cholesterol and triglycerides. The aim of this study was to determine the allelic and genotypic distributions of the APOA5-1131T>C (rs 662799) and the APOE HhaI polymorphisms and to identify the association of both individual and combined APOA5-APOE genetic variants and the risk for dyslipidemia in children and adolescents. We genotyped 53 dyslipidemic and 77 normolipidemic individuals. The total cholesterol, triglycerides and HDL cholesterol were determined enzymatically. For APOA5 polymorphism, the presence of the allele C confers an individual risk for dyslipidemia (OR = 2.38, 95% CI = 1.15-4.89; P = 0.018). No significant differences were observed for lipid parameters among the APOA5 groups, except for a higher value of HDLc (P = 0.024) in C-carriers. The allelic and genotypic frequencies of APOE polymorphism were similar between groups and did not increase the susceptibility for dyslipidemia. None of the combined APOA5-APOE polymorphisms increased risk for dyslipidemia. We demonstrated an association between APOA5-1131T>C polymorphism and dyslipidemia in children and adolescents. This finding may be useful to guide new studies with genetic markers down a path toward a better characterization of the genetic risk factors for dyslipidemia and atherosclerotic diseases.

Systematic review of abdominal surgery for chronic idiopathic constipation.

AIM: Constipation is a common problem which increases in prevalence with age. Chronic constipation is complex and difficult to treat. Some patients will not respond to pharmacological therapy and therefore surgery may be considered. A systematic review of the literature was performed to determine the outcome of surgery. METHOD: Published papers were identified by a search of The Cochrane Library, MEDLINE, CINAHL and EMBASE. They were reviewed and the data were extracted. RESULTS: Forty-eight papers were identified, including 1443 patients. Eleven different procedures were described. There was inconsistency in reporting. In 65% of patients the mean frequency of defaecation increased from 1.1 to 19.7 evacuations per week. Where laxative usage was reported (971 patients), it was found that 88% of patients did not need them postoperatively. Early complications included ileus (0-16%), infection (0-13%) and anastomotic leakage (0-22%). Patient satisfaction and quality of life scores were high. Only 30% of studies included data on preoperative psychological assessment. CONCLUSION: Surgery improves constipation and is associated with a higher degree of patient satisfaction, but the quality of studies was very variable. Future controlled trials should examine the ideal therapeutic approach for different patient groups.

Predictors of the outcome of percutaneous nerve evaluation for faecal incontinence.

BACKGROUND: The aim was to identify patient-related and operative factors that might predict the outcome of percutaneous nerve evaluation (PNE). METHODS: Demographic data (age, sex, body mass index), primary cause of incontinence, number and type of incontinence episodes, results of endoanal ultrasonography and manometry, and operative factors from 244 patients who underwent PNE for faecal incontinence were reviewed. Each factor was assessed according to the outcome, and explored by univariable and multivariable analysis to identify predictors. RESULTS: Some 191 patients (78.3 per cent) had a successful PNE. A low amplitude of sensory threshold during PNE (odds ratio (OR) 0.69 (95 per cent confidence interval 0.59 to 0.81); P < 0.001) and lead placement anterior to the sacral cortex (OR 9.06 (4.70 to 17.45); P < 0.001) were positive predictive factors for successful outcome of PNE. Neither a defect nor an abnormality of either the external (OR 0.88 (0.39 to 1.97); P = 0.749) or internal (OR 0.62 (0.27 to 1.42); P = 0.255) anal sphincter was a negative predictive factor. Demographic variables, number of incontinence episodes and the motor response threshold did not predict outcome. CONCLUSION: No preoperative predictor of PNE outcome could be identified. Predictors were limited to operative lead placement and sensory response during PNE.

Management of fecal incontinence in adults.

This article summarises the findings from the Conservative Management of Faecal Incontinence in Adults Committee of the International Consultation on Incontinence. We conducted comprehensive literature searches using the following keywords combined with the relevant intervention: "anal, anorectal, bowel, faecal, fecal, rectal, stool" and "continent$ or incontinent$," Prevalence etimates for faecal or anal incontinence vary widely, from 2.2% to 2.5%. Expert opinion supports the use of general health education, patient teaching about bowel function and advice on lifestyle modification, but the evidence base is small. Unlike urinary incontinence, few "lifestyle" associations have been identified with FI and little is known about whether interventions designed to reduce potential risk factors might improve FI. The article summarises the evidence and recommendations from the committee for clinical practice and future research.

The need for manual evacuation and oral laxatives in the management of neurogenic bowel dysfunction after spinal cord injury: a randomized controlled trial of a stepwise protocol.

STUDY DESIGN: Randomised controlled trial. OBJECTIVES: High-quality evidence for interventions in bowel management (BM) after spinal cord injury (SCI) is lacking and BM programs are developed empirically. This randomized, controlled trial compared usual care with a stepwise protocol based on earlier published work to examine whether systematic use of less invasive interventions could reduce the need for oral laxatives and invasive interventions such as manual evacuation, and improve BM outcomes in individuals with chronic SCI. SETTING: United Kingdom. METHODS: In all, 68 individuals were recruited (35 in intervention group), median age 47 years (range 24-73 years), median duration of injury 16 years (range 1-47 years). Bowel diaries were maintained for a maximum of 6 weeks while the intervention group followed a stepwise protocol designed to test interventions singly and in combination. Measures of quality of life and preferences for different bowel care interventions were recorded. RESULTS: The stepwise protocol did not improve BM outcomes; fecal incontinence was more frequent (P=0.04); the need for oral laxatives and invasive interventions was not reduced (P=0.4). Bowel care took consistently longer in the intervention group. CONCLUSIONS: The study findings support the need for manual evacuation in BM and provide evidence of acceptability of the technique to SCI individuals. For some individuals oral laxatives are an essential part of management. The results are in contrast with previous studies in younger samples with shorter duration of injury.

Identification of an E-selectin region critical for carbohydrate recognition and cell adhesion.

E-selectin elicits cell adhesion by binding to the cell surface carbohydrate, sialyl Lewis X (sLe(x)). We evaluated the effects of mutations in the E-selectin lectin domain on the binding of a panel of anti-E-selectin mAbs and on the recognition of immobilized sLe(x) glycolipid. Functional residues were then superimposed onto a three-dimensional model of the E-selectin lectin domain. This analysis demonstrated that the epitopes recognized by blocking mAbs map to a patch near the antiparallel beta sheet derived from the NH2 and COOH termini of the lectin domain and two adjacent loops. Mutations that affect sLe(x) binding map to this same region. These results thus define a small region of the E-selectin lectin domain that is critical for carbohydrate recognition.