Intestinal failure-associated liver disease: Current challenges in screening, diagnosis, and parenteral nutrition considerations.

Intestinal failure-associated liver disease (IFALD) is a serious life-limiting complication that can occur throughout the clinical course of intestinal failure and its management by parenteral nutrition (PN). Despite this, there is a lack of a standardized definition for IFALD, which makes this insidious condition increasingly difficult to screen and diagnose in clinical practice. Attenuating the progression of liver disease before the onset of liver failure is key to improving morbidity and mortality in these patients. This requires timely detection and promptly addressing reversible factors. Although there are various noninvasive tools available to the clinician to detect early fibrosis or cirrhosis in various chronic liver disease states, these have not been validated in the patient population with IFALD. Such tools include biochemical composite scoring systems for fibrosis, transient elastography, and dynamic liver function tests. This review article aims to highlight the existing real need for an accurate, reproducible method to detect IFALD in its early stages. In addition, we also explore the role PN plays in the pathogenesis of this complex multifactorial condition. Various aspects of PN administration have been implicated in the etiology of IFALD, including the composition of the lipid component, nutrient excess and deficiency, and infusion timing. We aim to highlight the clinical relevance of these PN-associated factors in the development of IFALD and how these can be managed to mitigate the progression of IFALD.

Effectiveness of the "Evidence-Based Scientific Exercise Guidelines" in Increasing Cardiorespiratory Fitness, Cardiometabolic Health, and Muscle Strength in Acute Spinal Cord Injury Rehabilitation: A Systematic Review.

Objective: To determine the effect of exercise and physical activity interventions that meet current guideline recommendations on cardiorespiratory fitness, cardiometabolic health, and muscle strength in adults in the acute stage (<1 year post onset) of spinal cord injury (SCI) rehabilitation. Data Sources: Six electronic databases (PubMed, CINAHL, SPORTDiscus, Google Scholar, National Institute Clinical Excellence, World Health Organization) were searched (January 2016-March 2022) to extend a previously published review. Study Selection: Included studies implemented exercise interventions in the acute stage of SCI rehabilitation participants which met the exercise guidelines and measured cardiorespiratory fitness, cardiometabolic health, and strength outcomes. Data Extraction: Titles and abstracts were screened against eligibility criteria and duplicates removed using EndNote X8. Full texts were independently assessed and results presented in a Preferred Reporting Items for Systematic Reviews and Meta-Analyses flowchart. Data extraction was completed on included studies by 2 reviewers (L.R. and V.B.) using a modified Cochrane Group form. Data Synthesis: Data were synthesized, appraised using the Modified Downs & Black checklist and presented in narrative and tabular format. This review was registered on PROSPERO (Register ID:CRD42021249441). Of the 1255 studies, 4 were included, featuring 108 total participants <1-year post-SCI. Functional electrical stimulation cycle ergometry reduced muscle atrophy after 3 months training and increased lean body mass after 6 months. Resistance training increased muscle peak torque, perceived muscle strength and function. Aerobic exercise interventions did not increase cardiorespiratory fitness. Conclusions: Interventions meeting the exercise guidelines did not increase cardiorespiratory fitness but were shown to improve cardiometabolic health and perceived muscle strength and function in adults in the acute stage of SCI rehabilitation. Further empirical research using standardized outcome measures are required to explore the effectiveness of aerobic exercise and strengthening interventions in acute stage of SCI rehabilitation to support the development of exercise guidelines.

Investigating the Relationship between Home Parenteral Support and Needs-Based Quality of Life in Patients with Chronic Intestinal Failure: A National Multi-Centre Longitudinal Cohort Study.

Home parenteral support (HPS) is an essential but potentially burdensome treatment that can affect quality of life (QoL). The aims of this longitudinal study were to understand whether any changes in HPS over time were associated with QoL. The Parenteral Nutrition Impact Questionnaire (PNIQ) was used, and data were collected on HPS prescribed at three time points. Data were analysed using multi-level mixed regression models presented as effect size and were adjusted for confounders. Study recruited 572 participants from 15 sites. Of these, 201 and 145 completed surveys at second and third time-points, respectively. PNIQ score was out of 20 with a higher score indicating poorer QoL. Any reduction in HPS infusions per week was associated with an improved PNIQ score of -1.10 (95% CI -2.17, -0.02) unadjusted and -1.34 (95% CI -2.45, -0.24) adjusted. Per day change to the number of infusions per week was associated with a change in the PNIQ score of 0.32 (95% CI -0.15, 0.80) unadjusted and 0.34 (95% CI -0.17, 0.85) adjusted. This is the largest national study to demonstrate improvements in QoL associated with HPS reduction over time using an HPS-specific and patient-centric tool, adding unique data for use of therapies in intestinal failure.

Small bowel villous atrophy due to immune-checkpoint inhibitors: report of two cases and literature review.

The differential diagnosis of non-coeliac enteropathies (NCEs) is challenging and includes a wide range of aetiologies. Drug-induced NCEs are relatively common and characterized by duodenal villous atrophy, which resolves upon suspension of the offending drug. Immune-checkpoint inhibitors (ICIs), targeting molecules involved in the activation of cytotoxic T cells by targeting, for example, PD-1, PD-L1 and CTLA4, are increasingly used for many types of cancers. Adverse events occurring in the gastrointestinal tract have been described, predominantly in the form of immune-mediated colitis mimicking inflammatory bowel disease. Small bowel involvement whilst on ICI therapy is also possible, though less well described. Herein, we describe two cases of enteropathy with villous atrophy and negative coeliac serology due to ICIs: a 65-year-old man affected by stage IV pulmonary adenocarcinoma under treatment with pembrolizumab and an 18-year-old woman affected by stage IV auricular melanoma who was treated with nivolumab. We also provide a review of the current literature describing small bowel involvement during therapy with ICIs, alone or in combination, for different types of solid tumours. Implications for clinical practice include considering the possibility of small bowel involvement in oncological patients treated with ICIs and the inclusion of ICIs amongst the iatrogenic causes of NCE with villous atrophy. Enteropathies due to ICIs may also represent a pathogenetic model for the understanding of the molecular mechanisms leading to villous atrophy in NCE.

Impact of home parenteral nutrition on family members: A national multi-centre cross-sectional study.

BACKGROUND & AIMS: Home parenteral nutrition (HPN) is a necessary treatment for patients with chronic, type 3, intestinal failure (IF). HPN often requires lifestyle adaptations, which are likely to affect quality of life (QoL) in both patients and family members. The aim of this study was to identify the level of burden on family members who are involved with HPN care and to understand specific factors that contribute to any burden. METHODS: Patients over the age of 18 and receiving HPN were identified in IF clinics from multiple centres across the U.K. Eligible patients were asked to complete the parenteral nutrition impact questionnaire (PNIQ) to assess their QoL, while family members were asked to complete the burden scale for family caregivers (BSFC). Logistical regression was undertaken giving adjusted odds ratios (aOR). RESULTS: 678 participants completed the survey representing 339 patients with their appointed family member. Mean PNIQ score was 11.53 (S.D. 5.5), representing a moderate impact of HPN on patients' QoL. On the BSFC scale, 23% of family members reported a moderate to very severe subjective burden indicating an increased risk of psychosomatic symptoms. After adjusting for age and gender, predictors of BSFC included: family members self-reported health status using the EuroQol visual analogue scale (aOR 19.91, 95% CI 1.69, 233.99, p = 0.017) and support received by health services (aOR = 5.83, 95% CI = 1.93, 17.56, p = 0.002). Employment status, disease type, number of nights on HPN and length of time on HPN were not associated with BSFC. CONCLUSIONS: Family members with a poor health status or lack of support by health service were more likely to have a moderate to very severe subjective burden. Tailored support from the multi-professional IF team may reduce the burden experienced by family members of people dependent on HPN.

Prevalence of unmet needs for spasticity management in care home residents in the East Midlands, United Kingdom: a cross-sectional observational study.

OBJECTIVE: To establish the prevalence of unmet need for spasticity management in care home residents in two counties of the United Kingdom. DESIGN: Cross-sectional observational study with a six-month follow-up arm for participants with identified unmet needs. SETTING: 22 care homes in Derbyshire and Nottinghamshire. SUBJECTS: 60 care home residents with upper motor neuron syndrome-related spasticity. INTERVENTIONS: No intervention. When unmet needs around spasticity management were identified, the participant's general practitioner was advised of these in writing. MAIN MEASURES: Resistance to Passive Movement Scale to assess spasticity; recording of (a) the presence of factors which may aggravate spasticity, (b) potential complications of spasticity, (c) spasticity-related needs and (d) current interventions to manage spasticity. Two assessors judged the presence or absence of needs for spasticity management and whether these needs were met by current care. RESULTS: Out of 60 participants, 14 had no spasticity-related needs; 46 had spasticity-related needs; 11 had needs which were being met by current care and 35 participants had spasticity-related needs at baseline which were not being met by their current care. These were most frequently related to the risk of contracture development or problems with skin hygiene or integrity in the upper limb. In total, 6 participants had one or more pressure sores and 35 participants had one or more established joint contractures. A total of 31 participants were available for follow-up. Informing general practitioners of unmet needs resulted in no change to spasticity management in 23/31 cases. CONCLUSION: Care home residents in this study had high levels of unmet need for spasticity management.

Needs-based quality of life in adults dependent on home parenteral nutrition.

BACKGROUND & AIMS: Home parenteral nutrition (HPN) provides life sustaining treatment for people with chronic intestinal failure. Individuals may require HPN for months or years and are dependent on regular intravenous infusions, usually 12-14 h overnight between 1 and 7 days each week. This regime can have adverse impact on the life of people dependent on the treatment. The aim of this study was to establish mean values for the Parenteral Nutrition Impact Questionnaire (PNIQ) and to determine the effect of disease, frequency of infusions per week and patient characteristics on quality of life of patients fed HPN. METHOD: The PNIQ was distributed to patients across nine UK HPN clinics. Data were analysed using linear regression, with PNIQ score as the dependent variable and potential confounders as independent variables. Unadjusted and adjusted models are presented. Higher PNIQ scores reflect poorer quality of life. RESULTS: Completed questionnaires were received from 466 people dependent on HPN. Mean PNIQ score was 11.04 (SD 5.79). A higher PNIQ score (effect size 0.52, CI 0.184 to 0.853) was recorded in those dependent on a higher frequency of HPN infusions per week. Respondents with cancer had a similar mean PNIQ score to those with inflammatory bowel disease (mean 10.82, SD 6.00 versus 11.04, SD 5.91). Those with surgical complications reported a poorer QoL (effect size 3.03, CI 0.642 to 5.418) and those with severe gastro-intestinal dysmotility reported a better QoL (effect size -3.03, CI -5.593 to -0.468), compared to other disease states. CONCLUSIONS: This large cohort study of quality of life in chronic intestinal failure demonstrates that HPN impacts individuals differently depending on their underlying disease. Furthermore, since the number of HPN infusions required per week is inversely related to an individual's needs-based quality of life, therapies that reduce PN burden should lead to an improvement in QoL.

Guidance on the management of diarrhoea during cancer chemotherapy.

Diarrhoea induced by chemotherapy in cancer patients is common, causes notable morbidity and mortality, and is managed inconsistently. Previous management guidelines were based on poor evidence and neglect physiological causes of chemotherapy-induced diarrhoea. In the absence of level 1 evidence from randomised controlled trials, we developed practical guidance for clinicians based on a literature review by a multidisciplinary team of clinical oncologists, dietitians, gastroenterologists, medical oncologists, nurses, pharmacist, and a surgeon. Education of patients and their carers about the risks associated with, and management of, chemotherapy-induced diarrhoea is the foundation for optimum treatment of toxic effects. Adequate--and, if necessary, repeated--assessment, appropriate use of loperamide, and knowledge of fluid resuscitation requirements of affected patients is the second crucial step. Use of octreotide and seeking specialist advice early for patients who do not respond to treatment will reduce morbidity and mortality. In view of the burden of chemotherapy-induced diarrhoea, appropriate multidisciplinary research to assess meaningful endpoints is urgently required.

Efficacy of taurolidine on the prevention of catheter-related bloodstream infections in patients on home parenteral nutrition.

PURPOSE: To assess the efficacy of taurolidine (TauroLockTM) line locks on the prevention of catheter-related bloodstream infections (CRBSI) in patients on home parenteral nutrition (HPN). METHODS: In our unit, any patient with ≥2 CRBSIs in six months is considered for TauroLockTM (2% taurolidine and 4% citrate) line locks. All such patients from May 2007 until January 2012 were identified, along with associated CRBSI rates. CRBSI was defined by differential time to positivity for positive blood cultures. CRBSIs were grouped into pre-taurolidine use and post-taurolidine commencement for each patient and the infection rate per 1000 catheter days calculated. Results were analyzed using Wilcoxon two-sided test. RESULTS: A total of nine patients were included (two men and seven women) with a median age of 51 (range 43-82) years. Infection rates after commencing taurolidine decreased markedly in all patients studied. The median CRBSI rate prior to taurolidine use was 6.39 per 1000 catheter days. This decreased to a median CRBSI rate of 0 per 1000 catheter days after commencing taurolidine. CONCLUSIONS: Taurolidine is no substitute for careful aseptic technique. However, it is clearly effective at preventing CRBSIs and should be used in patients with recurrent infections to reduce morbidity.

Nutritional management of Crohn's disease.

Nutritional care and therapy forms an integral part of the management of patients with Crohn's disease (CD). Nutritional deficiencies result from reduced oral intake, malabsorption, medication side effects and systemic inflammation due to active disease. Enteral nutrition has a role in support for the malnourished patient, as well as in primary therapy to induce and maintain remission. The use of parenteral nutrition in CD is mainly limited to the preoperative setting or for patients with intestinal failure, but does not offer any additional advantage over EN in disease control. Dietary modifications, including elimination-reintroduction diets and a low fermentable, oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) diet may improve symptoms but there are currently no data to suggest that these approaches have any role in the induction or maintenance of remission.

Use of arteriovenous fistulae for home parenteral nutrition--a review of the literature.

PURPOSE: Delivery of home parenteral nutrition (HPN), traditionally via tunneled central venous catheters (CVCs) is associated with several complications, the commonest being catheter related bloodstream infections. We have reviewed the literature to investigate the use of arteriovenous fistulae (AVF) as a viable alternative to traditional routes for long-term parenteral nutrition (PN). METHODS: A literature search was performed using the Medline database, PubMed and a Google Scholar search. Search terms (keywords) used were: parenteral AND nutrition AND arteriovenous AND fistula for Title and Abstract. Our search yielded 12 articles (1972-2012). Two were excluded because of foreign language and difficult retrieval. The final yield was 10 papers RESULTS: There were four case reports, six original papers (one Swedish, one French--both excluded), one abstract and one letter to the editor. There were 19 native AVF, 11 bovine grafts (BG), four synthetic grafts (SG) and 10 autologous venous grafts (AVG). The maximum recorded length of use was 86, 54, 16.7 and 300 months, respectively. Complication rates per fistula calculated from literature were 0.47, 1.18, 2.0 and 0.3 respectively. Apart from these results, a recent retrospective study (13) of 62 AVFs for HPN patients revealed an infection rate far lower than all types of CVC and a slightly higher occlusion rate than long-term CVCs. CONCLUSIONS: There is relatively little data regarding this method. AVFs have been used successfully for HPN in patients with poor vasculature, on hemodialysis or recurrent line sepsis. This technique perhaps warrants more thorough exploration. Further research is required.

A multidisciplinary approach to management of autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED).

We present a case of an 18-year-old Caucasian man with a rare autosomal recessive disorder called autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED). This patient had manifestations of all clinical components of this multisystemic disease which included intestinal failure secondary to autoimmune enteropathy. We present a unique multidisciplinary management for this genetic condition. Although patients with APECED do not always have all the disease components (a total of eight exist), the majority have at least 3-5 components. This excludes the psychosexual implications which are often ignored. This case highlights the importance of (1) management of APECED in a multidisciplinary nature that includes a gastroenterologist, immunologist, endocrinologist, dietitians, etc and the (2) management of intestinal failure component of APECED is best suited in a specialist intestinal failure unit where expertise is available for complex malabsorption disorders.

WITHDRAWN: Medical treatments in the short term management of reflux oesophagitis.

BACKGROUND: Oesophagitis arises when reflux of acid from the stomach into the oesophagus causes mucosal inflammation. It is a common problem and a systematic review on the optimum treatment would be useful. OBJECTIVES: To assess the effectiveness of proton pump inhibitors (PPIs), H2 receptor antagonists (H2RAs), prokinetic therapy, sucralfate and placebo in healing oesophagitis or curing reflux symptoms or both. To compare adverse effects with the different treatments. SEARCH STRATEGY: We searched MEDLINE, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials and the National Research Register until December 2004 and reference lists of articles. We also contacted manufacturers and researchers in the field. SELECTION CRITERIA: Randomised controlled trials assessing the healing of oesophagitis or reflux symptoms or both. Treatment involving PPIs, H2RAs, prokinetics, sucralfate and combinations either in comparison to another treatment regimen or to placebo for 2 and 12 weeks. DATA COLLECTION AND ANALYSIS: Two reviews independently assessed trial quality and extracted data. MAIN RESULTS: We included 134 trials involving 35,978 oesophagitis participants. Five RCTs evaluated standard dose of PPI versus placebo in 965 participants. There was a statistically significant benefit of taking standard dose PPI therapy compared to placebo in healing of oesophagitis (RR = 0.22; 95% CI 0.15 to 0.31). Ten RCTs reported on the outcome for H2RA versus placebo evaluating 1241 participants. There was statistically significant benefit of taking H2RA compared to placebo in healing of oesophagitis (RR 0.74,95% CI = 0.66 to 0.84). Three RCTs evaluated prokinetic therapy versus placebo in 198 participants. There was no statistically significant benefit of taking prokinetic therapy compared to placebo in healing of oesophagitis (RR 0.71, 95% CI 0.46 to 1.10). Twenty six RCTs reported the outcome for PPI versus H2RA or H2RA plus prokinetics, evaluating 4032 participants. There was statistically significant benefit of taking PPI therapy compared to H2RA or H2RA plus prokinetics in healing of oesophagitis (RR 0.51, 95% CI 0.44 to 0.59). AUTHORS' CONCLUSIONS: PPI therapy is the most effective therapy in oesophagitis but H2RA therapy is also superior to placebo. There is a paucity of evidence on prokinetic therapy but no evidence that it is superior to placebo.

WITHDRAWN: Medical treatments for the maintenance therapy of reflux oesophagitis and endoscopic negative reflux disease.

BACKGROUND: Gastro-oesophageal reflux disease (GORD) - reflux of stomach contents +/- bile into the oesophagus causing symptoms such as heartburn and acid reflux - is a common relapsing and remitting disease which often requires long-term maintenance therapy. Patients with GORD may have oesophagitis (inflammation of the oesophagus) or a normal endoscopy (endoscopy negative reflux disease or ENRD). OBJECTIVES: To assess the effects of continuous maintenance therapy in adults with GORD (both ENRD and healed oesophagitis). SEARCH STRATEGY: We searched Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 2, 2003), MEDLINE (1966 to 2003), EMBASE (1980 to 2003), CINAHL (1982-2003), and the National Research Register (Issue 2, 2003) and reference lists of articles. We also contacted manufacturers and researchers in the field. SELECTION CRITERIA: Randomised controlled studies comparing PPIs, H2RAs, prokinetics, sucralfate and combinations either in comparison to another treatment regimen or to placebo in adults with reflux oesophagitis and ENRD. DATA COLLECTION AND ANALYSIS: One author extracted data from included trials and a second author carried out an unblinded check. Two authors independently assessed trial quality. Study authors were contacted for additional information. MAIN RESULTS: Maintenance of patients with healed oesophagitis: For a healing dose of PPI (generally the standard dose given by the manufacturer) versus placebo, the relative risk (RR) for oesophagitis relapse was 0.26 (95% confidence interval (CI) 0.19 to 0.36); versus H2RAs the RR was 0.36 (95% CI 0.28 to 0.46) and versus maintenance PPIs the RR was 0.63 (95% CI 0.55 to 0.73). However overall adverse effects were also more common and headaches were more common when comparing healing PPIs to H2RAs.For a maintenance dose of PPI (half of the standard dose) versus placebo, the RR for oesophagitis relapse was 0.46 (95% CI 0.38 to 0.57) and versus H2RAs the RR was 0.57 (95% CI 0.47 to 0.69). Overall adverse effects were more common.H2RAs were of marginal help but beneficial for symptomatic relief. Prokinetics and sucralfate were also more effective than placebo.For ENRD patients: Limited data with one RCT showed benefit for omeprazole 10 mg once daily over placebo (RR 0.4; 95% CI 0.29 to 0.53). AUTHORS' CONCLUSIONS: The findings in this review support the long-term treatment of oesophagitis to prevent relapse, both endoscopically and symptomatically. Healing doses of PPIs are more effective than all other therapies, although there is an increase in overall adverse effects compared to placebo, and headache occurrence compared to H2RAs. H2RAs prevent relapse more effectively than placebo, demonstrating a role for PPI-intolerant patients. Prokinetics and sucralfate both show benefit over placebo, but the former is no longer licenced. There is only limited data for ENRD.

TENS and FES for sensory impairment and gait dysfunction following removal of spinal cord ependymoma--a case report.

BACKGROUND: Sensory deficits are commonly reported following the resection of spinal cord tumours. The use of transcutaneous electrical nerve stimulation (TENS) as augmented sensory input is described in the research literature but rarely in the clinical literature. Functional electrical stimulation (FES) is used for people with motor impairments rather than sensory impairments. METHOD AND RESULTS: This case report describes the use of TENS and FES for a patient with severe sensory loss and mild weakness in the right leg following the removal of an intramedullary spinal cord tumour. The patient was able to walk more quickly and more confidently when using TENS and FES in combination. She consistently reported greater benefits from TENS alone compared to FES alone and continued to use TENS delivered via a sock electrode at six months after surgery. CONCLUSION: The use of TENS as a sensory stimulus was an invaluable component of this patient's treatment, allowing her to engage in a more challenging balance and gait programme at an earlier stage in her rehabilitation. Combining FES with TENS was also useful and allowed treatment to address motor and sensory impairments concurrently during functional activity.

Acupuncture for back pain, knee pain and insomnia in transverse myelitis - a case report.

This case report describes the use of acupuncture for back pain, knee pain and insomnia in a 49 year old woman with a recent diagnosis of transverse myelitis with paraplegia, sensory disturbance, and bladder and bowel dysfunction. She was receiving intensive in-patient multi-disciplinary rehabilitation but was struggling to participate fully due to pain and poor sleep quality. She received a course of acupuncture in addition to standard care and reported substantial benefits including reduction in pain, improved sleep and mood, and reduction in daytime fatigue. Effective symptom control allowed this patient to participate more fully in her rehabilitation programme. Reduction of knee pain and sleep disturbance was maintained until discharge, 15 weeks after the last acupuncture treatment. This case report suggests that acupuncture may be an option to consider for other patients with pain or sleep disturbance that is interfering with their rehabilitation programme.

Proteomic screening of a cell line model of esophageal carcinogenesis identifies cathepsin D and aldo-keto reductase 1C2 and 1B10 dysregulation in Barrett's esophagus and esophageal adenocarcinoma.

Esophageal adenocarcinoma (EA) incidence is increasing rapidly and is associated with a poor prognosis. Identifying biomarkers of disease development and progression would be invaluable tools to inform clinical practice. Two-dimensional polyacrylamide gel electrophoresis was used to screen 10 esophageal cell lines representing distinct stages in the development of esophageal cancer. Thirty-three proteins were identified by MALDI-TOF-MS which demonstrated differences in expression across the cell lines. Western blotting and qRT-PCR confirmed increased cathepsin D and aldo-keto reductases 1C2 and 1B10 expression in metaplastic and dysplastic cell lines. Expression of these proteins was further assessed in esophageal epithelium from patients with nonerosive (NERD) and erosive gastro-esophageal reflux disease, Barrett's esophagus (BE) and EA. When compared with normal epithelium of NERD patients, (i) cathepsin D mRNA levels demonstrated a stepwise increase in expression (p<0.05) in erosive, metaplastic and EA tissue; (ii) AKR1B10 expression increased (p<0.05) 3- and 9-fold in erosive and Barrett's epithelium, respectively; and (iii) AKR1C2 levels increased (p<0.05) in erosive and Barrett's epithelium, but were reduced (p<0.05) in EA. These proteins may contribute to disease development via effects on apoptosis, transport of bile acids and retinoid metabolism and should be considered as candidates for further mechanistic and clinical investigations.

Comparison of the effect of two types of acupuncture on quality of life in secondary progressive multiple sclerosis: a preliminary single-blind randomized controlled trial.

OBJECTIVE: To compare the effect of two types of acupuncture on the quality of life of individuals with secondary progressive multiple sclerosis and provide preliminary evidence regarding the safety of this intervention for this population. DESIGN: Preliminary single-blind randomized controlled trial. SETTING: Outpatient attendance at rehabilitation unit. PARTICIPANTS: Fourteen participants with secondary progressive multiple sclerosis. INTERVENTIONS: Chinese medical acupuncture or minimal acupuncture. Participants received 10 treatments over five weeks. MEASURES: Multiple Sclerosis Impact Scale 29, Fatigue Severity Scale and General Health Questionnaire 12 were measured pre and post intervention. Adverse events and other responses during treatment were recorded prospectively. RESULTS: Participants receiving minimal acupuncture demonstrated statistically significant greater improvement in the Multiple Sclerosis Impact Scale 29 psychological subscale compared with those receiving Chinese medical acupuncture in an intention-to-treat analysis (P=0.04), with mean change in Chinese acupuncture group of 6.0 (SD 13.9) and in minimal acupuncture group of 23.0 (SD 21.0). No other statistically significant difference between the groups was found. No major adverse events were noted. Minor adverse events such as lower limb muscle spasms or pain were noted in some participants in both intervention groups. CONCLUSION: Minimal acupuncture resulted in greater improvement of Multiple Sclerosis Impact Scale 29 psychological subscale compared with Chinese medical acupuncture. No other differences between the groups were found. In view of the small sample these results are not conclusive. This study provides preliminary evidence to suggest that acupuncture is safe for people with secondary progressive multiple sclerosis. A large-scale trial is required to provide more definitive evidence.

Medical treatments in the short term management of reflux oesophagitis.

BACKGROUND: Oesophagitis arises when reflux of acid from the stomach into the oesophagus causes mucosal inflammation. It is a common problem and a systematic review on the optimum treatment would be useful. OBJECTIVES: To assess the effectiveness of proton pump inhibitors (PPIs), H2 receptor antagonists (H2RAs), prokinetic therapy, sucralfate and placebo in healing oesophagitis or curing reflux symptoms or both. To compare adverse effects with the different treatments. SEARCH STRATEGY: We searched MEDLINE, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials and the National Research Register until December 2004 and reference lists of articles. We also contacted manufacturers and researchers in the field. SELECTION CRITERIA: Randomised controlled trials assessing the healing of oesophagitis or reflux symptoms or both. Treatment involving PPIs, H2RAs, prokinetics, sucralfate and combinations either in comparison to another treatment regimen or to placebo for 2 and 12 weeks. DATA COLLECTION AND ANALYSIS: Two reviews independently assessed trial quality and extracted data. MAIN RESULTS: We included 134 trials involving 35,978 oesophagitis participants. Five RCTs evaluated standard dose of PPI versus placebo in 965 participants. There was a statistically significant benefit of taking standard dose PPI therapy compared to placebo in healing of oesophagitis (RR = 0.22; 95% CI 0.15 to 0.31). Ten RCTs reported on the outcome for H2RA versus placebo evaluating 1241 participants. There was statistically significant benefit of taking H2RA compared to placebo in healing of oesophagitis (RR 0.74,95% CI = 0.66 to 0.84). Three RCTs evaluated prokinetic therapy versus placebo in 198 participants. There was no statistically significant benefit of taking prokinetic therapy compared to placebo in healing of oesophagitis (RR 0.71, 95% CI 0.46 to 1.10). Twenty six RCTs reported the outcome for PPI versus H2RA or H2RA plus prokinetics, evaluating 4032 participants. There was statistically significant benefit of taking PPI therapy compared to H2RA or H2RA plus prokinetics in healing of oesophagitis (RR 0.51, 95% CI 0.44 to 0.59). AUTHORS' CONCLUSIONS: PPI therapy is the most effective therapy in oesophagitis but H2RA therapy is also superior to placebo. There is a paucity of evidence on prokinetic therapy but no evidence that it is superior to placebo.