A multi-national survey of experience and attitudes towards commencing home parenteral nutrition for patients with advanced cancer.

INTRODUCTION: Advanced cancer (AC) is increasingly an indication for home parenteral nutrition (HPN) but an area with possible variation in practice between geographical locations. The aims of this study are to explore the views and experiences of international multi-disciplinary teams to determine opinions and practices. METHODS: An online questionnaire was developed with members of the Home Artificial Nutrition and Chronic Intestinal Failure interest group of the European Society for Clinical Nutrition and Metabolism (ESPEN) and distributed to colleagues involved in managing patients with AC on HPN. RESULTS: A total of 220 responses were included from 5 continents including 36 countries, with 90% of all responses from Europe. Predicted survival was a key factor influencing the decision to commence HPN for most respondents 152/220 (75%), with the majority of participants reporting that patients should have a predicted survival of ≥3 months if considered for HPN (≥3 months: n = 124, 56% vs. <3 months: n = 47, 21%, p < 0.001). However, most respondents were not confident about predicting overall survival in more than 50% of cases (confident n = 40, 23% vs not confident n = 135, 77%, p < 0.001). Barriers to utilising HPN in AC included colleagues' objections (n = 91, 46%), lack of local expertise (n = 55, 28%) and funding restrictions (n = 34, 17%). CONCLUSIONS: Significant consensus was observed regarding AC as indication for HPN, while areas of variation exist. Survival prognostication is often used as an indication for commencing HPN in people with AC, although the majority of respondents were not confident in prognosticating, suggesting better clinical prognostication tools will be of assistance. Further studies are also required to better understand the obstacles faced by clinical teams to commencing HPN that may explain variations in clinical practice between countries, as well as adressing variation in funding.

Dealing with loss: food and eating in women with ovarian cancer on parenteral nutrition.

BACKGROUND: Malignant bowel obstruction is a common complication of ovarian cancer, resulting in limited oral intake. Home parenteral nutrition (HPN) may be offered to patients in this condition to meet nutritional requirements. However, it is not known how they experience being unable to eat. The present study reports how patients related to food when receiving HPN. METHODS: The investigation was a qualitative study underpinned by phenomenology with women with advanced ovarian cancer in bowel obstruction receiving parenteral nutrition. Interview transcripts were analysed thematically guided by the techniques of Van Manen. RESULTS: We recruited 20 women to the study. Participants were interviewed a maximum of four times and a total of 39 in-depth longitudinal interviews were conducted. Participants could tolerate minimal amounts of food, if they had a venting gastrostomy. Not being able to eat engendered a sense of sadness and loss, and most women found it challenging to be in the presence of others eating. They adopted strategies to cope, which included fantasising about food and watching cookery programmes. These approaches were not a long-term solution; either participants came to terms with their loss or the strategies became less effective in providing relief. CONCLUSIONS: Home parenteral nutrition meets the nutritional requirements of patients with malignant bowel obstruction but cannot replace the non-nutritive functions of food. Healthcare professionals can offer a patient-centred approach by acknowledging the difficulties that patients may face and, wherever possible, encourage them to focus on the positive benefits of interacting with people rather than the loss of eating on social occasions.

AML1 protein interacts with influenza A virus neuraminidase and upregulates IFN-ß response in infected mammalian cells.

Neuraminidase (NA) is an integral membrane protein of influenza A virus (IAV) and primarily aids in the release of progeny virions, following the intracellular viral replication cycle. In an attempt to discover new functions of NA, we conducted a classical yeast two-hybrid screen and found acute myeloid leukaemia marker 1 (AML1) as a novel interacting partner of IAV-NA. The interaction was further validated by co-immunoprecipitation in IAV-infected cells and in an in vitro coupled transcription/translation system. Interestingly, we found an increase in the expression of AML1 upon IAV infection in a dose-dependent manner. As expected, we also observed an increase in the IFN-ß levels, the first line of defence against viral infections. Subsequently, when AML1 was downregulated using siRNA, the IFN-ß levels were found to be remarkably reduced. Our study also shows that AML1 is induced upon IAV infection and results in the induction of IFN-ß. Thus, AML1 is proposed to be an important player in IFN induction and has a role in an antiviral response against IAV infection. SIGNIFICANCE AND IMPACT OF THE STUDY: Influenza epidemics and pandemics are constant threats to human health. Development of antiviral therapeutics has focused on important and major IAV proteins as targets. However, the rate at which this virus mutates makes the task challenging. Thus, next-generation approaches aim at host cellular proteins that aid the virus in its replication. This study reports a new host-virus interaction, of acute myeloid leukaemia marker 1 (AML1) with influenza A neuraminidase (IAV-NA). We have found that this interaction has a direct effect on the upregulation of host IFN-ß response. Further studies may lead to a greater understanding of this new innate defence pathway in infected cells.

Metabolic bone diseases in intestinal failure.

Metabolic bone diseases are a group of conditions that are common complications in patients with intestinal failure. These may occur as a result of the underlying condition, leading to intestinal failure, particularly inflammatory conditions such as Crohn's disease and their associated treatments including corticosteroids. Malabsorption, as a result of a loss of enterocyte mass or gut function, of many nutrients, including vitamin D, may further compound metabolic bone problems, and there has been historical contamination of parenteral nutrition with aluminium that has prevented normal bone metabolism contributing to osteoporosis. This review looks at the diagnosis and current management of bone health in patients with intestinal failure.

A novel discharge pathway for patients with advanced cancer requiring home parenteral nutrition.

BACKGROUND: The use of home parenteral nutrition (HPN) for palliative indications is increasing internationally and is the leading indication in some countries. Discharge on HPN can be complex in metabolically unstable patients and requires intestinal failure expertise. METHODS: Between 2012 and 2018, we performed a retrospective analysis aiming to assess the impact of a novel remote discharge pathway for palliative HPN patients. This was evaluated using a quality improvement approach. RESULTS: One hundred and twenty-five patients with active malignancy [mean (range) age 58 (25-80) years] were referred to the intestinal failure unit (IFU) for remote discharge. Of 82 patients were discharged from the oncology Centre on HPN using the pathway. The remaining 43 patients either declined HPN or the Oncology team felt that the patient became too unwell for HPN or died prior to discharge. There was an increase in patients referred for remote discharge from 13 in 2012 to 43 in 2017. The mean number of days between receipt of referral by the IFU to discharge on HPN from the oncology centre reduced from 29.4 days to 10.1 days. Following remote discharge, the mean number of days on HPN was 215.9 days. Catheter-related blood stream infection rates in this cohort were very low at 0.169 per 1000 catheter days. CONCLUSIONS: This is the first study to demonstrate the remote safe, effective and rapid discharge of patients requiring palliative HPN between two hospital sites. This allows patients with a short prognosis more time in their desired location.

Antimicrobial photodynamic activity of toluidine blue encapsulated in mesoporous silica nanoparticles against Pseudomonas aeruginosa and Staphylococcus aureus.

In the present study, the antimicrobial and antibiofilm efficacy of toluidine blue (TB) encapsulated in mesoporous silica nanoparticles (MSN) was investigated against Pseudomonas aeruginosa and Staphylococcus aureus treated with antimicrobial photodynamic therapy (aPDT) using a red diode laser 670 nm wavelength, 97.65 J cm-2 radiant exposure, 5 min). Physico-chemical techniques (UV-visible (UV-vis) absorption, photoluminescence emission, excitation, and FTIR) and high-resolution transmission electron microscopy (HR-TEM) were employed to characterize the conjugate of TB encapsulated in MSN (TB MSN). TB MSN showed maximum antimicrobial activities corresponding to 5.03 and 5.56 log CFU ml-1 reductions against P. aeruginosa and S. aureus, respectively, whereas samples treated with TB alone showed 2.36 and 2.66 log CFU ml-1 reductions. Anti-biofilm studies confirmed that TB MSN effectively inhibits biofilm formation and production of extracellular polymeric substances by P. aeruginosa and S. aureus.

Synthesis and antimicrobial photodynamic effect of methylene blue conjugated carbon nanotubes on E. coli and S. aureus.

Catheter-related bloodstream infections (CRBSIs) are one of the leading causes of high morbidity and mortality in hospitalized patients. The proper management, prevention and treatment of CRBSIs rely on the understanding of these highly resistant bacterial infections. The emergence of such a challenge to public health has resulted in the development of an alternative antimicrobial strategy called antimicrobial photodynamic therapy (aPDT). In the presence of a photosensitizer (PS), light of the appropriate wavelength, and molecular oxygen, aPDT generates reactive oxygen species (ROS) which lead to microbial cell death and cell damage. We investigated the enhanced antibacterial and antibiofilm activities of methylene blue conjugated carbon nanotubes (MBCNTs) on biofilms of E. coli and S. aureus using a laser light source at 670 nm with radiant exposure of 58.49 J cm-2. Photodynamic inactivation in test cultures showed 4.86 and 5.55 log10 reductions in E. coli and S. aureus, respectively. Biofilm inhibition assays, cell viability assays and EPS reduction assays showed higher inhibition in S. aureus than in E. coli, suggesting that pronounced ROS generation occurred due to photodynamic therapy in S. aureus. Results from a study into the mechanism of action proved that the cell membrane is the main target for photodynamic inactivation. Comparatively higher photodynamic inactivation was observed in Gram positive bacteria due to the increased production of free radicals inside these cells. From this study, we conclude that MBCNT can be used as a promising nanocomposite for the eradication of dangerous pathogens on medical devices.

The Sydney Heart Bank: improving translational research while eliminating or reducing the use of animal models of human heart disease.

The Sydney Heart Bank (SHB) is one of the largest human heart tissue banks in existence. Its mission is to provide high-quality human heart tissue for research into the molecular basis of human heart failure by working collaboratively with experts in this field. We argue that, by comparing tissues from failing human hearts with age-matched non-failing healthy donor hearts, the results will be more relevant than research using animal models, particularly if their physiology is very different from humans. Tissue from heart surgery must generally be used soon after collection or it significantly deteriorates. Freezing is an option but it raises concerns that freezing causes substantial damage at the cellular and molecular level. The SHB contains failing samples from heart transplant patients and others who provided informed consent for the use of their tissue for research. All samples are cryopreserved in liquid nitrogen within 40 min of their removal from the patient, and in less than 5-10 min in the case of coronary arteries and left ventricle samples. To date, the SHB has collected tissue from about 450 failing hearts (>15,000 samples) from patients with a wide range of etiologies as well as increasing numbers of cardiomyectomy samples from patients with hypertrophic cardiomyopathy. The Bank also has hearts from over 120 healthy organ donors whose hearts, for a variety of reasons (mainly tissue-type incompatibility with waiting heart transplant recipients), could not be used for transplantation. Donor hearts were collected by the St Vincent's Hospital Heart and Lung transplantation team from local hospitals or within a 4-h jet flight from Sydney. They were flushed with chilled cardioplegic solution and transported to Sydney where they were quickly cryopreserved in small samples. Failing and/or donor samples have been used by more than 60 research teams around the world, and have resulted in more than 100 research papers. The tissues most commonly requested are from donor left ventricles, but right ventricles, atria, interventricular system, and coronary arteries vessels have also been reported. All tissues are stored for long-term use in liquid N or vapor (170-180 °C), and are shipped under nitrogen vapor to avoid degradation of sensitive molecules such as RNAs and giant proteins. We present evidence that the availability of these human heart samples has contributed to a reduction in the use of animal models of human heart failure.

Pharmacogenetics of ABCB5, ABCC5 and RLIP76 and doxorubicin pharmacokinetics in Asian breast cancer patients.

This study investigated the impact of ABCB5, ABCC5 and RLIP76 polymorphisms on doxorubicin pharmacokinetics in Asian breast cancer patients (N=62). Direct sequencing was performed to screen for previously identified ABCC5 polymorphisms as well as polymorphisms in the exons and exon-intron boundaries of ABCB5 and RLIP76 genes. Genotype-phenotype correlations were analyzed using Mann-Whitney U-test. The homozygous variant allele at the ABCC5 g.+7161G>A (rs1533682) locus was significantly associated with higher doxorubicin clearance (g.+7161AA vs g.+7161GG, CL/BSA (Lh-1m-2): 30.34 (25.41-33.60) vs 22.46 (15.04-49.4), P=0.04). Homozygosity for the reference allele at the ABCC5 g.-1679T>A locus was associated with significantly higher doxorubicinol exposure (g.-1679TT vs g.-1679TA, AUC0-∞/dose/BSA (hm-5): 15.48 (6.18-67.17) vs 8.88 (3.68-21.71), P=0.0001). No significant influence of the three newly identified ABCB5 polymorphisms (c.2T>C, c.343A>G and c.1573G>A) on doxorubicin pharmacokinetics was observed. No polymorphisms were identified in the RLIP76 gene. These findings suggest that ABCC5 polymorphisms may explain partially the interpatient variability in doxorubicin disposition.

Outcome of intestinal failure after bariatric surgery: experience from a national UK referral centre.

BACKGROUND/OBJECTIVES: Bariatric surgery for morbid obesity provides sustained weight loss. Complications of bariatric surgery include severe nutritional decline, but minimal data describing occurrence and outcome of intestinal failure (IF) exist. SUBJECTS/METHODS: All patients referred to one of the UK's National IF units (IFU) are prospectively entered onto a database; case notes were assessed for bariatric surgery details, IF onset, outcomes, resulting intestinal anatomy, mortality and catheter-related bloodstream infections (CRBSIs). RESULTS: A total of six patients (mean referral age 54.0 years; 95% confidence interval (CI): 44.6-63.4; 5 female) were identified with IF after bariatric surgery from 457 patients (total cohort) managed on home parenteral nutrition (HPN) at the IFU between 2008 and 2014. In all, 6/6 had Roux-en-Y gastric bypass bariatric surgery. Median (range) time from index bariatric surgery to IF development was 28.7 months (1.7-106). IF aetiology was internal herniation (4/6), ischaemia (1/6) and anastomotic leak (1/6); all patients required HPN for a median of 26.4 months (15.3-34.7). CRBSI occurred on 7 occasions in 3 patients, equivalent to 1.5/1000 catheter days in these 6 compared with 0.32/1000 in the 451 IFU HPN patients during this time period. In all, 0/6 patients died, 6/6 had continuity restored in a median of 16.5 months (6.5-32.5) after IF diagnosis and 3/6 (50%) were weaned from PN by a median of 2.2 months (0.6-12.8). CONCLUSIONS: Bariatric surgery, an increasingly common operation, can be associated with IF necessitating long-term HPN. The cohort presented had a higher CRBSI compared with other HPN patients; more stringent approaches to catheter care may be required in this patient group, although more collective data are required.

Nucleoprotein of influenza A virus negatively impacts antiapoptotic protein API5 to enhance E2F1-dependent apoptosis and virus replication.

Apoptosis of host cells profoundly influences virus propagation and dissemination, events that are integral to influenza A virus (IAV) pathogenesis. The trigger for activation of apoptosis is regulated by an intricate interplay between cellular and viral proteins, with a strong bearing on IAV replication. Though the knowledge of viral proteins and mechanisms employed by IAV to induce apoptosis has advanced considerably of late, we know relatively little about the repertoire of host factors targeted by viral proteins. Thus, identification of cellular proteins that are hijacked by the virus will help us not only to understand the molecular underpinnings of IAV-induced apoptosis, but also to design future antiviral therapies. Here we show that the nucleoprotein (NP) of IAV directly interacts with and suppresses the expression of API5, a host antiapoptotic protein that antagonizes E2F1-dependent apoptosis. siRNA-mediated depletion of API5, in NP-overexpressed as well as IAV-infected cells, leads to upregulation of apoptotic protease activating factor 1 (APAF1), a downstream modulator of E2F1-mediated apoptosis, and cleavage of caspases 9 and 3, although a reciprocal pattern of these events was observed on ectopic overexpression of API5. In concordance with these observations, annexin V and 7AAD staining assays exhibit downregulation of early and late apoptosis in IAV-infected or NP-transfected cells on overexpression of API5. Most significantly, while overexpression of API5 decreases viral titers, cellular NP protein as well as mRNA levels in IAV-infected A549 cells, silencing of API5 expression causes a steep rise in the same parameters. From the data reported in this manuscript, we propose a proapoptotic role for NP in IAV pathogenesis, whereby it suppresses expression of antiapoptotic factor API5, thus potentiating the E2F1-dependent apoptotic pathway and ensuring viral replication.

The nucleoprotein of influenza A virus induces p53 signaling and apoptosis via attenuation of host ubiquitin ligase RNF43.

The interplay between influenza virus and host factors to support the viral life cycle is well documented. Influenza A virus (IAV) proteins interact with an array of cellular proteins and hijack host pathways which are at the helm of cellular responses to facilitate virus invasion. The multifaceted nature of the ubiquitination pathway for protein regulation makes it a vulnerable target of many viruses including IAV. To this end we conducted a yeast two-hybrid screen to search for cellular ubiquitin ligases important for influenza virus replication. We identified host protein, RING finger protein 43 (RNF43), a RING-type E3 ubiquitin ligase, as a novel interactor of nucleoprotein (NP) of IAV and an essential partner to induce NP-driven p53-mediated apoptosis in IAV-infected cells. In this study, we demonstrate that IAV leads to attenuation of RNF43 transcripts and hence its respective protein levels in the cellular milieu whereas in RNF43 depleted cells, viral replication was escalated several folds. Moreover, RNF43 polyubiquitinates p53 which further leads to its destabilization resulting in a decrease in induction of the p53 apoptotic pathway, a hitherto unknown process targeted by NP for p53 stabilization and accumulation. Collectively, these results conclude that NP targets RNF43 to modulate p53 ubiquitination levels and hence causes p53 stabilization which is conducive to an enhanced apoptosis level in the host cells. In conclusion, our study unravels a novel strategy adopted by IAV for utilizing the much conserved ubiquitin proteasomal pathway.

The role of computed tomography in evaluating body composition and the influence of reduced muscle mass on clinical outcome in abdominal malignancy: a systematic review.

It is estimated that there were 3.45 million new cases and 1.75 million deaths from cancer in Europe in 2012. Colorectal cancer was one of the most common cancers, accounting for 13% of new cases and 12.2% of all deaths. Conditions causing reduced muscle mass, such as sarcopenia, can increase the morbidity and mortality of people with cancer. Computed tomography (CT) scans can provide accurate, high-quality information on body composition, including muscle mass. To date, there has been no systematic review on the role of CT scans in identifying sarcopenia in abdominal cancer. This review aimed to examine the role of CT scans in determining the influence of reduced muscle mass on clinical outcome in abdominal cancer. A systematic review of English-language articles published in 2000 or later was conducted. Articles included cohort, randomised controlled trials and validation studies. Participants were people diagnosed with abdominal cancer who had undergone a CT scan. Data extraction and critical appraisal were undertaken. Ten cohort studies met the inclusion criteria. Seven studies demonstrated that low muscle mass was significantly associated with poor clinical outcome, with six specifically demonstrating reduced survival rates. Eight studies demonstrated that a greater number of patients (27.3-66.7%) were identified as sarcopenic using CT scans compared with numbers identified as malnourished using body mass index. CT scans can identify reduced muscle mass and predict negative cancer outcomes in people with abdominal malignancies, where traditional methods of assessment are less effective.

Management of large bowel obstruction with self-expanding metal stents. A multicentre retrospective study of factors determining outcome.

AIM: UK cancer guidelines recommend patients with colonic obstruction due to suspected malignancy be considered for stenting with a self-expanding metal stent (SEMS). Considerable variation in practice exists due to a lack of expertise, technical difficulties and other, as yet ill-defined features. This retrospective multi-centre study aims to determine the outcome following colonic stenting for large bowel obstruction and identify factors associated with successful intervention. METHOD: A regional programme of colonic stenting for large bowel obstruction, in five UK centres from 2005 to 2010 was evaluated for outcome including technical and clinical success, survival, complications and reoperation. RESULTS: A SEMS was inserted in 334 patients, including 264 (79.0%) for palliation and 52 (15.6%) as a bridge to surgery. Technical success was achieved in 292 (87.4%) patients, with 46 (13.8%) experiencing a complication or technical failure. Reoperation was required in 39 (14.8%) patients stented for palliation of colorectal cancer of whom 16 (6.1%) subsequently required a colostomy. A one-stage primary anastomosis was achieved in 35 (67.3%) of the 52 patients undergoing stenting as a bridge to resection. Technical success did not vary by indication or site of obstruction (P = 0.60) but was higher for operators who had performed more than 10 procedures (OR 3.34, P = 0.001). ASA grade ≥3 predicted a worse clinical outcome (OR 0.43, P = 0.04). The through-the-scope (TTS) endoscopy technique was more successful than radiological placement alone (90.3% vs 74.8%, P < 0.001). CONCLUSION: Experienced operators using a TTS technique achieved a better outcome for the emergency management of large bowel obstruction. Older, sicker patients and those with extracolonic and benign strictures fared less well.

Nutritional screening of elderly patients: a health improvement approach to practice.

INTRODUCTION: Almost 60% of elderly care in-patients are at risk of malnutrition. Malnourished patients have poorer clinical outcomes and this is a key factor with respect to prolonging the length of stay. Since 2003, the Malnutrition Universal Screening Tool (MUST) has been advocated as a method for identifying these at-risk patients. Screening should take place on admission; however, the Trust has set a stretch target of aiming to document the score accurately within 6 h of admission. METHODS: Three 'care of the elderly' wards participated in the project. Each month, the timeliness (within 6 h of admission) and accuracy (compared to a dietician assessment) of the MUST scores on the wards were reviewed. Plan-Do-Study-Act cycles were used to rapidly test changes in the ward areas. Tests included a study day, one-to-one ward-based nutrition training, a focus on the use of alternative anthropometric measurements, the development of a training pack and the identification of the challenges for undertaking accurate and timely assessments. RESULTS: Baseline data identified that a MUST was documented in <60% of patients within 6 h of admission and that only 70% were accurate. After implementation of the change package, all the wards achieved an improvement and documented MUST within 6 h of admission; one ward achieved 90% accuracy in the scores. CONCLUSIONS: Ward teams receiving training and monthly feedback of their results creates ownership, momentum and maintains enthusiasm for striving to reach stretch targets. The team continues to work on improving accurate nutritional screening across the Trust by using quality improvement methodologies.

Radiation enteritis leading to intestinal failure: 1994 patient-years of experience in a national referral centre.

BACKGROUND/OBJECTIVES: Chronic radiation enteritis (RE) has been reported in up to 20% of patients receiving pelvic radiotherapy and can lead to intestinal failure (IF), accounting for 3.9% of new registrants for home parenteral nutrition (HPN) in the UK annually. Our aim is to report nutritional and survival outcomes for patients with RE referred to a national IF unit. SUBJECTS/METHODS: A retrospective study of all new admissions over a 13-year period at the Intestinal Failure Centre, Manchester, UK. Data are presented as median (range). RESULTS: Twenty-three (3.8%) of 611 patients were admitted with IF secondary to RE. The primary site of malignancy was genitourinary in 17 (74%) patients. Radiotherapy was administered 9.5 (1-42) years previously. Patients underwent 2 (1-5) laparotomies prior to intestinal failure unit (IFU) admission. Twelve (52%) patients were admitted with intestinal obstruction and 11 (48%) with intractable weight loss and/or high output fistulae/stomas. Additional conditions contributing to IF were noted in 11 (48%) patients. Twenty-two (96%) patients had 2 (1-5) laparotomies prior to IFU referral. At discharge, 5 (22%) patients resumed oral diet without the need for artificial nutrition support, 3 (13%) required enteral feeding and 13 (56%) commenced HPN. The 10-year survival of the patient cohort was 48.2%. CONCLUSIONS: Surgical intervention is infrequently required, whereas the majority of patients with IF secondary to RE require long-term HPN. The judicious use of surgery in selected patients, coupled with an aggressive medical strategy to detect and treat contributing factors, and optimal enteral feeding may allow a modest proportion of patients with IF secondary to RE to achieve independence from PN.

Optimal patient education for cancer pain: a systematic review and theory-based meta-analysis.

PURPOSE: Previous systematic reviews have found patient education to be moderately efficacious in decreasing the intensity of cancer pain, but variation in results warrants analysis aimed at identifying which strategies are optimal. METHODS: A systematic review and meta-analysis was undertaken using a theory-based approach to classifying and comparing educational interventions for cancer pain. The reference lists of previous reviews and MEDLINE, PsycINFO, and CENTRAL were searched in May 2012. Studies had to be published in a peer-reviewed English language journal and compare the effect on cancer pain intensity of education with usual care. Meta-analyses used standardized effect sizes (ES) and a random effects model. Subgroup analyses compared intervention components categorized using the Michie et al. (Implement Sci 6:42, 2011) capability, opportunity, and motivation behavior (COM-B) model. RESULTS: Fifteen randomized controlled trials met the criteria. As expected, meta-analysis identified a small-moderate ES favoring education versus usual care (ES, 0.27 [-0.47, -0.07]; P = 0.007) with substantial heterogeneity (I² = 71 %). Subgroup analyses based on the taxonomy found that interventions using "enablement" were efficacious (ES, 0.35 [-0.63, -0.08]; P = 0.01), whereas those lacking this component were not (ES, 0.18 [-0.46, 0.10]; P = 0.20). However, the subgroup effect was nonsignificant (P = 0.39), and heterogeneity was not reduced. Factoring in the variable of individualized versus non-individualized influenced neither efficacy nor heterogeneity. CONCLUSIONS: The current meta-analysis follows a trend in using theory to understand the mechanisms of complex interventions. We suggest that future efforts focus on interventions that target patient self-efficacy. Authors are encouraged to report comprehensive details of interventions and methods to inform synthesis, replication, and refinement.

Review article: the assessment and management of chronic severe gastrointestinal dysmotility in adults.

BACKGROUND: The characterisation and management of chronic severe gastrointestinal (GI) dysmotility are challenging. It may cause intestinal failure requiring home parenteral nutrition (HPN). AIMS: To review the presentation, aetiology, characterisation, management and outcome of chronic severe GI dysmotility, and to suggest a pragmatic management algorithm. METHODS: PubMed search was performed up to December 2012 using appropriate search terms, restricted to human articles and reviewed for relevance. Segmental dysmotility, acute ileus, functional syndromes and non-English articles were excluded. Evidence and recommendations were evaluated using the GRADE system. RESULTS: In total, 721 relevant articles were reviewed. A coherent and definitive picture is hampered by overlapping classification systems using multi-modal characterisation methods, subject to pitfalls and some requiring further validation. The literature is confined to case series with no randomised trials. Fewer than 20% undergo full thickness jejunal biopsy, which are otherwise labelled idiopathic. However, in studies with up to 80% biopsy rates, neuromuscular abnormalities may be found in 90%. Between 14% and 50% will require HPN, comprising 8-14% of all HPN patients, of which 2/3 are primary/idiopathic and 1/3 secondary, with scleroderma being the leading secondary cause. Ten-year  mortality ranges from 13% to 35% and is worst in elderly scleroderma patients. Management includes limited treatments for secondary causes, prokinetics, symptom palliation, psychological support, nutrition, hydration and judicious surgery. CONCLUSIONS: Severe dysmotility often remains idiopathic. It is rarely possible to alter disease trajectory; consequently, prognosis may be poor. Multi-disciplinary teams in a specialist setting can improve outcomes. Graded recommendations are enumerated and a pragmatic algorithm is suggested.

Clinical and histological resolution of collagenous sprue following gluten-free diet and discontinuation of non-steroidal anti-inflammatory drugs (NSAIDs).

Collagenous sprue is a rare small bowel enteropathy that has overlapping clinical features with coeliac disease; it is commonly associated with arthritic autoimmune conditions, which often require non-steroidal anti-inflammatory drugs (NSAIDs). In the limited published literature available, there are putative suggestions of a link between NSAID use and collagen deposition in intestinal subepithelia in such patients. The authors present a case of a 43-year-old woman with long-standing NSAID use for autoimmune polyarthropathy and positive coeliac antibodies. However, distal duodenal biopsies revealed a thickened band of subepithelial collagen with villous atrophic appearances consistent with collagenous sprue. The patient was treated with a gluten-free diet and her NSAIDs were discontinued. After 6 months, her gastrointestinal symptoms had resolved with complete histological resolution of the collagenous subepithelial bands and villous atrophy on duodenal biopsy.