An open label feasibility study of a nutrition and exercise app-based solution in cirrhosis.

Background: Nutrition and exercise are the mainstay of therapy for the prevention and treatment of frailty in cirrhosis. This pilot study assessed feasibility of the online delivery of an app-based semi-supervised nutrition and exercise intervention in this population. Methods: The 11-week pilot recruited adults with cirrhosis who owned internet-connected devices. Patients were encouraged to participate in exercise sessions 3× per week including a combination of online group exercise (weekly) and home-based follow-along exercise (biweekly). They also participated in group nutrition classes (five sessions) and one-to-one exercise and nutrition check-ins delivered through the app. Primary outcome measures pertained to program feasibility: recruitment, retention, adherence, and satisfaction. Exploratory measures included physical performance (liver frailty index [LFI], 6-minute walk test [6MWT]), health behaviour domains, and quality of life. Results: Twenty three patients completed baseline measures. Of these, 18 (72%) completed end of study measures (mean MELD-Na, 9.2; female, 44.4%). Over 70% of participants fulfilled 75% or more of the feasibility criteria. Satisfaction with the program was high (mean, 89%). Exercise program modifications were required for 17 patients to accommodate health events or abilities. Exploratory evaluation showed improvement in the LFI and the 6MWT by -0.58-units (95% CI: -0.91 to -0.25) and 46.0 m (95% CI: 22.7-69.3) respectively without changes in quality of life or health behaviour domains. Conclusions: Outcomes demonstrate feasibility of the app-based delivery of programming with promising exploratory impact on efficacy for physical performance. Findings can guide the design of a large-scale app-based randomized controlled trials in cirrhosis.

Identifying opportunities for hepatic encephalopathy self-management: A mixed methods systematic review and synthesis.

Background: Hepatic encephalopathy (HE) in cirrhosis is an extremely challenging complication for patients and care partners. To identify potentially modifiable factors to enhance HE self-management strategies, we conducted a synthesis of quantitative and qualitative research about real-world HE behaviours, knowledge, and experiences. Methods: Using the EPPI-Centre's mixed methods synthesis procedure, a systematic literature search in five databases was completed; methods of selected articles underwent critical appraisal followed by descriptive analysis and coded line-by-line of content. Through refutational translation, the findings from the quantitative and qualitative syntheses were juxtaposed to highlight congruencies, incongruencies, or gaps. These findings informed generation of cross-analytical themes that were transformed into action statements. Results: The quantitative narrative review of synthesis (n = 17) generated four themes (patients had low awareness of HE and low treatment adherence rates, physicians had a non-uniform approach to non-pharmaceutical therapies). Meta-aggregation of qualitative data from six articles yielded three themes (patients and care partners had low levels of HE awareness, were unfamiliar with HE self-management, and were adherent to treatments). Comparison of findings revealed three congruencies, two gaps, and one incongruency. The combined synthesis yielded two self-management themes: universal patient-oriented cirrhosis HE education and ensuring each health care encounter systematically addresses HE to guarantee health care is continuously modified to meet their needs. Conclusions: By drawing on elements of Bloom's Taxonomy and distributed knowledge networks, deliberate patient-oriented HE messaging at all health care encounters is greatly needed to improve health outcomes and reduce care burdens related to HE.

Identification of urinary biomarkers of colorectal cancer: Towards the development of a colorectal screening test in limited resource settings.

BACKGROUND: African colorectal cancer (CRC) rates are rising rapidly. A low-cost CRC screening approach is needed to identify CRC from non-CRC patients who should be sent for colonoscopy (a scarcity in Africa). OBJECTIVE: To identify urinary metabolite biomarkers that, combined with easy-to-measure clinical variables, would identify patients that should be further screened for CRC by colonoscopy. Ideal metabolites would be water-soluble and easily translated into a sensitive, low-cost point-of-care (POC) test. METHODS: Liquid-chromatography mass spectrometry (LC-MS/MS) was used to quantify 142 metabolites in spot urine samples from 514 Nigerian CRC patients and healthy controls. Metabolite concentration data and clinical characteristics were used to determine optimal sets of biomarkers for identifying CRC from non-CRC subjects. RESULTS: Our statistical analysis identified N1, N12-diacetylspermine, hippurate, p-hydroxyhippurate, and glutamate as the best metabolites to discriminate CRC patients via POC screening. Logistic regression modeling using these metabolites plus clinical data achieved an area under the receiver-operator characteristic (AUCs) curves of 89.2% for the discovery set, and 89.7% for a separate validation set. CONCLUSIONS: Effective urinary biomarkers for CRC screening do exist. These results could be transferred into a simple, POC urinary test for screening CRC patients in Africa.

An Evaluation of Online Cirrhosis-related Information Intended for Patients and Caregivers.

With nearly 70% of American adults seeking online health information,1 the internet represents a powerful space to provide patients with evidence-based, usable education about their chronic conditions. Although effective patient-oriented communication recommendations are available, the accessibility, reliability, and accuracy of online health content is largely unmonitored or evaluated. In a complex chronic disease, such as cirrhosis, understanding the online information landscape specific to patients can provide insight into resources that are available to support their self-management behaviors and to fill knowledge gaps.

A randomized controlled trial of a multicomponent online stress reduction intervention in inflammatory bowel disease.

Background: Psychological stress negatively impacts inflammatory bowel disease (IBD) outcomes. Patients have prioritized access to online interventions; yet, the data on these have been limited by mixed in-person/online interventions, low adherence, and non-randomized controlled trial (RCT) design. Objectives: We assessed the efficacy of and adherence to a 12-week online multicomponent stress reduction intervention in IBD. Design: This is a RCT. Methods: Adult participants on stable IBD medical therapy with elevated stress levels from four centers were randomized to intervention or control groups. Intervention participants received a 12-week online program including a weekly yoga, breathwork and meditation video (target 2-3 times/week), a weekly cognitive behavioral therapy/positive psychology informed video activity, and weekly 10-min check-ins by a study team member. Control participants received weekly motivational messages by email. All patients received standard of care IBD therapy. The primary outcome was Cohen's Perceived Stress Scale (PSS). Secondary outcomes evaluated mental health, resilience, health-related quality of life (HRQoL), symptom indices, acceptability, adherence, and inflammatory biomarkers. Analysis of covariance was used to determine between-group differences. Results: Of 150 screened patients, 101 were randomized to the intervention (n = 49) and control (n = 52) groups (mean age: 42.5 ± 14.1 years; M:F 1:3, 48% with ulcerative colitis and 52% with Crohn's disease). The between-group PSS improved by 22.4% (95% confidence interval, 10.5-34.3, p < 0.001). Significant improvements were seen in mental health, resilience, and HRQoL measures, with a median satisfaction score of 89/100 at the end of the 12 weeks. In the 44/49 patients who completed the intervention, 91% achieved program adherence targets. Conclusion: This 12-week online intervention improved perceived stress, mental health, and HRQoL, but did not impact IBD symptom indices or inflammatory biomarkers. The program was readily adopted and adhered to by participants with high retention rates. After iterative refinement based on participant feedback, future studies will evaluate the impact of a longer/more intense intervention on disease course. Registration: ClinicalTrials.gov Identifier NCT03831750. Plain Language Summary: An online stress reduction intervention in inflammatory bowel disease patients improves stress, mental health, and quality of life People with inflammatory bowel disease (IBD) have high levels of stress, anxiety, and depression. Although IBD patients have expressed the need for online mental wellness interventions, the existing data to support these interventions in IBD are limited. In this trial, 101 IBD patients had the chance to participate in a 12-week online stress reduction intervention. In those patients randomly selected to participate in the online intervention, each week they received the following: a 20- to 30-min yoga, breathwork, and meditation video that they were asked to do 2-3 times a week, a 10- to 20-min mental wellness activity they were asked to do once during the week, and a 10-min telephone check-in with a study team member. Participants who were not selected to use the online intervention received a weekly motivational message by email. In all, 90 of the 101 participants (89%) completed the study with the mean age of participants being 43 years and the majority being females (75%). Ninety-one percent of participants who completed the intervention met the program target of doing the yoga, breathwork, and meditation video at least 2 times per week. Significant improvements were seen in perceived stress (by 22.4%), depression (by 29.5%), anxiety (by 23.7%), resilience (by 10.6%), and quality of life (by 8.9%). No changes were seen in IBD severity or in blood markers of inflammation. In conclusion, this study demonstrates evidence that a 12-week online stress reduction intervention had low dropout rates, high adherence and beneficial effects on stress, mental health, and quality of life measures. Continued feedback will be sought from study participants and our IBD patient partners to refine the intervention and assess the impact in future studies of patients with active IBD, as well as the impact of a longer/more intense intervention.

The Assessment of Driving Fitness Using an On-Road Evaluation in Patients With Cirrhosis.

INTRODUCTION: The association between cirrhosis and driving performance is of particular clinical relevance because of the life-threatening safety issues both for the driver with cirrhosis and the general public. Study aims were to assess (i) driving competency through the use of an in-office computerized battery and on-road driving assessment (DriveABLE) and (ii) the association between minimal hepatic encephalopathy (MHE), in-office paper-pencil tools, and additional measures (e.g., frailty, depression, cognitive testing) with unsafe driving. METHODS: Patients were prospectively recruited from 2 tertiary care liver clinics. In-office tests and in-office and on-road assessments of driving competence were completed. The χ 2 test and 1-way analysis of variance were used to analyze differences among those with and without MHE. Logistic regression was used to evaluate predictors of an indeterminate/fail result on the in-office computerized driving assessment battery (DriveABLE Cognitive Assessment Tool [DCAT]). RESULTS: Eighty patients participated with a mean age of 57 years, 70% male, 75% Child-Pugh B/C, and 36% with a history of overt hepatic encephalopathy. Thirty percent met MHE criteria on both the psychometric hepatic encephalopathy score and the Stroop app tests. Only 2 patients (3%) were categorized as "unfit to drive" in the on-road driving test, one with MHE and the other without. Fifty-eight percent of the patients were scored as indeterminate/fail on the DCAT. This corresponded to a higher mean number of on-road driving errors (5.3 [SD 2.1] vs 4.2 [SD 1.6] in those who passed the DCAT, P = 0.01). Older age (odds ratio 1.3; confidence interval 1.1, 1.5; P = 0.001) and MHE by Stroop/psychometric hepatic encephalopathy score (odds ratio 11.0; confidence interval 2.3, 51.8; P = 0.002) were independently predictive of worse performance on the DCAT. DISCUSSION: Worse performance in in-office testing was associated with worse scores on a computerized driving assessment battery and more on-road driving errors, but in-office tools were insufficient to predict on-road driving failures. A diagnosis of MHE should not be used alone to restrict driving in patients with cirrhosis. At-risk patients require on-road driving tests under the supervision of driving regulatory agencies. Future studies should continue to refine and evaluate in-office or at-home testing to predict driving performance.

Heal-me PiONEer (personalized online nutrition and exercise): An RCT assessing 2 levels of app-based programming in individuals with chronic disease.

Background App-based strategies are a promising solution to deliver nutrition and exercise interventions during social distancing. With limited RCT data in individuals with chronic disease, further information is required both to determine impact, and to guide delivery. The Heal-Me app is an evidence-based, theoretically informed nutrition and exercise solution that can be tailored for use across a range of individuals with chronic disease. As compared to controls receiving educational material, the aim of this study is to assess the acceptability, effectiveness, and cost of Heal-Me app programming delivered alongside two levels of dietitian and exercise-specialist support. Methods Heal-Me PiONEer is a 12-week, 3-arm RCT with randomization to one of three study groups (n=72 per group, 216 total). Group 1 (control: educational material), Group 2 (Heal-Me app + virtual group dietitian/exercise-specialist sessions), Group 3 (Heal-Me app + virtual group and 1-to-1 dietitian/exercise-specialist sessions). Inclusion criteria: adults with cancer, chronic lung disease or status post-transplantation from liver or lung transplant; previous completion of an exercise rehabilitation program; access to an internet-connected device. Study outcomes measured at study weeks 0 and 12 include: Primary - Lower Extremity Functional Scale; Secondary - virtual physical function tests, loneliness, resilience, anxiety, well-being and health-related quality of life; Exploratory outcomes - protein intake, behavioral beliefs around exercise and nutrition, adherence, adverse events, acceptability, and cost-utility. Conclusions The Heal-Me PiONEer RCT holds promise to provide a comprehensive understanding of the delivery and impact of app-based nutrition and exercise programming in a diverse group of participants with chronic disease.

Assessing Patient Proficiency with Internet-Connected Technology and Their Preferences for E-Health in Cirrhosis.

There is a rapidly evolving need for e-health to support chronic disease self-management and connect patients with their healthcare teams. Patients with cirrhosis have a high symptom burden, significant comorbidities, and a range of psychological and cognitive issues. Patients with cirrhosis were assessed for their readiness and interest in e-health. Adults attending one of two outpatient cirrhosis clinics in Alberta were recruited. Eligible participants were not required to own or have experience with digital technologies or the Internet. Medical history, socioeconomic status, and attitudes regarding e-health, the Computer Proficiency Questionnaire, and the Mobile Device Proficiency Questionnaire were used to describe participants' knowledge and skills. Of the 117 recruited patients, 68.4% owned a computer and 84.6% owned a mobile device. Patients had mean proficiency scores of 72.8% (SD 25.9%) and 69.3% (SD 26.4%) for these devices, respectively. In multiple regression analyses, significant predictors of device proficiency were age, education, and household income. Most patients (78.7%) were confident they could participate in videoconferencing after training and most (61.5%) were interested in an online personalized health management program. This diverse group of patients with cirrhosis had technology ownership, proficiency, and online behaviours similar to the general population. Moreover, the patients were very receptive to e-health if training was provided. This promising data is timely given the unique demands of COVID-19 and its influence on self-management and healthcare delivery to a vulnerable population.

Pregnancy-Related Beliefs and Concerns of Inflammatory Bowel Disease Patients Modified After Accessing e-Health Portal.

OBJECTIVE: Poor inflammatory bowel disease (IBD)-specific reproductive knowledge is associated with concerns and medication noncompliance. Having shown an educational portal can improve knowledge, we evaluated its effectiveness for addressing IBD patients' reproductive and medication concerns. METHODS: Adult IBD participants (aged 18 to 45 years) were invited to access an e-health portal providing information on heritability, fertility, surgery, pregnancy outcomes, delivery, postpartum, and breastfeeding in the context of IBD and IBD medications. At pre-, post-, and 6+-month postintervention, participants completed a questionnaire on IBD-specific pregnancy concerns, medication concerns from the Beliefs About Medicines Questionnaire (BMQ), and medication adherence via the Medication Adherence Rating Scale (MARS). The Wilcoxon signed-rank test was used to compare median differences between scores (95% confidence). RESULTS: Demographics for 78 (70.3%) participants completing postintervention questionnaires: median age 29.3 (interquartile range: 25.6 to 32.9) years; 54 (69.2%) Crohn's disease; 21 (26.9%) ulcerative colitis; 63 (80.3%) females, 5 (7.9%) pregnant; and 19 (30.2%) previously pregnant. Postintervention, the median number of reproductive concerns decreased from 3 to 1, and remained stable 6+ months later (P < 0.001*). The median BMQ score decreased from 28 to 25, and remained stable 6+ months later (P = 0.032*). Participants adherent to medications increased from 82.4% to 87.8% postintervention (P = 0.099). CONCLUSION: Using an e-health portal may potentially reduce IBD-specific reproductive and medications concerns. An e-health portal is feasible as one component of managing IBD patient's reproductive and medication concerns during preconception and pregnancy.

Systematic review with meta-analysis: Nutritional screening and assessment tools in cirrhosis.

BACKGROUND & AIMS: Disease-related malnutrition is common in cirrhosis. Multiple studies have evaluated nutritional screening tools (NSTs, rapid bedside tests targeting who needs assessment) and nutritional assessment tools (NATs, used in diagnosing malnutrition) as predictors of clinical outcome in this population. We performed a systematic review and meta-analysis of this literature with the aim of summarising the varying definitions of malnutrition across studies, the available evidence for NSTs and the ability of NSTs and NATs to predict clinical outcomes in cirrhosis. METHODS: The primary outcome measures were pre- and post-transplant mortality with a range of secondary outcomes. Inclusion: cirrhosis over age 16. Exclusion: >25% with hepatocellular carcinoma, primarily laboratory test-based NATs or lack of screening, assessment or outcome criteria. RESULTS: Eight thousand eight hundred fifty patients were included across 47 studies. Only 3 studies assessed NSTs. Thirty-two definitions for malnutrition were utilised across studies. NATs predicted pre-transplant mortality in 69% of cases that were assessed with a risk ratio (RR) of 2.38 (95% CI 1.96-2.89). NATs were prognostic for post-transplant mortality only 28% of the times they were assessed, with a RR of 3.04 (95% CI 1.51-6.12). CONCLUSIONS: The cirrhosis literature includes limited data on nutrition screening and multiple definitions for what constitutes malnutrition using NATs. Despite this discordance, it is clear that malnutrition is a valuable predictor of pre-transplant mortality almost regardless of how it is defined. We require clinical and research consensus around the definition of malnutrition and the accepted processes and cut-points for nutrition screening and assessment in cirrhosis.

Advance Care Planning Preferences and Readiness in Cirrhosis: A Prospective Assessment of Patient Perceptions and Knowledge.

Background: In 2014, the province of Alberta launched a campaign to promote public awareness of advance care planning (ACP) and its associated two-part documentation-a Goals of care designation (GCD, a medical order written by a health care practitioner detailing wishes for care) and a personal directive (PD, a document naming a surrogate decision maker). Notably, unlike the GCD, the PD can be self-initiated independent of a health practitioner. Objective: Two years after the campaign, we aimed to assess knowledge and recall of participation in ACP among cirrhosis patients. Design/Setting: Consecutive adult cirrhosis patients attending one of two specialty cirrhosis clinics in Edmonton, Alberta, were surveyed. Results: Ninety-seven patients were included. Mean model for end-stage liver disease was 12. Although 97% of patients indicated it was extremely important to know the reality of their illness, only 53% understood that cirrhosis would affect their future quality of life. Thirty-three percent of patients had completed a PD and 14% had completed a GCD. Seventy-eight percent of patients believed a GCD was important to them and 85% preferred to complete it in an outpatient clinic setting. Only a minority of patients who had taken the initiative to complete a PD in the community also had a GCD. Conclusions: Despite efforts to raise awareness of and educate Albertans about ACP, <20% of cirrhosis patients have a completed GCD. Additional strategic prioritization is required in both patients and providers to ensure that health practitioner-facilitated ACP is carried out as standard-of-care in all patients with cirrhosis.

Comparative effectiveness and cost-effectiveness analysis of a urine metabolomics test vs. alternative colorectal cancer screening strategies.

PURPOSE: Despite the success of provincial screening programs, colorectal cancer (CRC) is still the third most common cancer in Canada and the second most common cause of cancer-related death. Fecal-based tests, such as fecal occult blood test (FOBT) and fecal immunochemical test (FIT), form the foundation of the provincial CRC screening programs in Canada. However, those tests have low sensitivity for CRC precursors, adenomatous polyps and have low adherence. This study evaluated the effectiveness and cost-effectiveness of a new urine metabolomic-based test (UMT) that detects adenomatous polyps and CRC. METHODS: A Markov model was designed using data from the literature and provincial healthcare databases for Canadian at average risk for CRC; calibration was performed against statistics data. Screening strategies included the following: FOBT every year, FIT every year, colonoscopy every 10 years, and UMT every year. The costs, quality adjusted life years (QALY) gained, and incremental cost-effectiveness ratios (ICERs) for each strategy were estimated and compared. RESULTS: Compared with no screening, a UMT strategy reduced CRC mortality by 49.9% and gained 0.15 life years per person at $42,325/life year gained in the base case analysis. FOBT reduced CRC mortality by 14.9% and gained 0.04 life years per person at $25,011/life year gained. FIT reduced CRC mortality by 35.8% and gained 0.11 life years per person at $25,500/life year while colonoscopy reduced CRC mortality by 24.7% and gained 0.08 life years per person at $50,875/life year. CONCLUSIONS: A UMT strategy might be a cost-effective strategy when used in programmatic CRC screening programs.

Systematic review of nutrition screening and assessment in inflammatory bowel disease.

BACKGROUND: Malnutrition is prevalent in inflammatory bowel disease (IBD). Multiple nutrition screening (NST) and assessment tools (NAT) have been developed for general populations, but the evidence in patients with IBD remains unclear. AIM: To systematically review the prevalence of abnormalities on NSTs and NATs, whether NSTs are associated with NATs, and whether they predict clinical outcomes in patients with IBD. METHODS: Comprehensive searches performed in Medline, CINAHL Plus and PubMed. Included: English language studies correlating NSTs with NATs or NSTs/NATs with clinical outcomes in IBD. Excluded: Review articles/case studies; use of body mass index/laboratory values as sole NST/NAT; age < 16. RESULTS: Of 16 studies and 1618 patients were included, 72% Crohn's disease and 28% ulcerative colitis. Four NSTs (the Malnutrition Universal Screening Tool, Malnutrition Inflammation Risk Tool (MIRT), Saskatchewan Inflammatory Bowel Disease Nutrition Risk Tool (SaskIBD-NRT) and Nutrition Risk Screening 2002 (NRS-2002) were significantly associated with nutritional assessment measures of sarcopenia and the Subjective Global Assessment (SGA). Three NSTs (MIRT, NRS-2002 and Nutritional Risk Index) were associated with clinical outcomes including hospitalizations, need for surgery, disease flares, and length of stay (LOS). Sarcopenia was the most commonly evaluated NAT associated with outcomes including the need for surgery and post-operative complications. The SGA was not associated with clinical outcomes aside from LOS. CONCLUSION: There is limited evidence correlating NSTs, NATs and clinical outcomes in IBD. Although studies support the association of NSTs/NATs with relevant outcomes, the heterogeneity calls for further studies before an optimal tool can be recommended. The NRS-2002, measures of sarcopenia and developments of novel NSTs/NATs, such as the MIRT, represent key, clinically-relevant areas for future exploration.

Non-invasive Point-of-Care Device To Diagnose Acute Mesenteric Ischemia.

Inadequate blood supply to the intestine can lead to acute mesenteric ischemia (AMI), with a mortality rate ranging from 60% to 90%. This high mortality rate is partially due to late detection and the lack of efficient early diagnostic tests. There is an urgent need for a point-of-care tool for immediate bedside diagnosis. Here we present for the first time a rapid and non-invasive electrochemical biosensor device based on non-faradic impedance spectroscopy to detect intestinal fatty-acid binding protein (I-FABP) as an indication of AMI. The electrochemical biosensors consist of gold interdigitated electrodes that were fabricated using photolithographic techniques on top of silicon dioxide substrates. The electrode surfaces were functionalized with an I-FABP capture antibody (CAnB) to entice the target protein, while gold nanoparticles (GNPs) functionalized with detection antibodies (DAnB-GNPs) were utilized as a novel mechanism to enhance the detection signal. Quantification of the I-FABP concentration in the medium depended on its attachment to CAnB and DAnB-GNPs in a sandwich manner, where the latter boosts the impedance signal through its binding to the I-FABP. This non-invasive non-faradic electric biosensor device demonstrates the potential for bench-to-bedside translation with the goal of decreasing morbidity and mortality from AMI.

Advance care planning (ACP) for specialists managing cirrhosis: A focus on patient-centered care.

Advance care planning (ACP) and goals of care designation (GCD) are being integrated into modern health care. In cirrhosis, uptake and adoption of these practices have been limited with physicians citing many perceived barriers and limitations. Recognizing the many tangible benefits of ACP and GCD processes in patients with life-limiting chronic diseases, the onus is on health practitioners to initiate and direct these conversations with their patients and surrogates. Drawing upon the literature and our experiences in palliative care and cirrhosis, we provide an actionable framework that can be readily implemented into a busy clinical setting by a practitioner. Conversation starters, visual aids, educational resources (for patients and practitioners), and videos of mock physician-patient scenarios are presented and discussed. Importantly, we have customized each of these tools to meet the unique health care needs of patients with cirrhosis. The inherent flexibility of our approach to ACP discussions and GCD can be further modified to accommodate practitioner preferences. CONCLUSION: In our clinics, this assemblage of "best practice tools" has been well received by patients and surrogates enabling us to increase the number of outpatients with cirrhosis who have actively contributed to their GCD before acute health events and are supported by well-informed surrogates. (Hepatology 2018;67:2025-2040).

Practical Considerations and the Intestinal Microbiome in Disease: Antibiotics for IBD Therapy.

The inflammatory bowel diseases, Crohn's and ulcerative colitis, have been treated with a range of antibiotics for inducing and maintaining remission, as well as the prevention of post-operative symptoms. To date, many studies have been performed assessing the efficacy of antibiotics when used alone, in combination with other antibiotics, or as an adjunctive therapy to other pharmaceutical treatments. Literature evidence supporting the use of antibiotics in IBD can be ambiguous, especially when considering the potential role of dysbiosis in the gastrointestinal tract. The review considers the systemic effect of antibiotics and the evidence base for their efficacy in the treatment of IBD.

Potential benefits of therapeutic use of ß2-adrenergic receptor agonists in neuroprotection and Parkinsonµs disease.

The ß2-adrenergic receptor (ß2AR) is a seven-transmembrane (7TM) G-protein coupled receptor that is expressed on cells of the pulmonary, cardiac, skeletal muscle, and immune systems. Previous work has shown that stimulation of this receptor on immune cells has profound effects on the regulatory activity of both adaptive and innate immune cells. This review examines the functional dichotomy associated with stimulation of ß2AR and microglial cells. As well, recent studies targeting these receptors with long-acting agonists are considered with respect to their therapeutic potential in management of Parkinsonµs disease.

An intervention program to reduce falls for adult in-patients following major lower limb amputation.

A qualitative and quantitative assessment was conducted regarding falls sustained by in-patients receiving rehabilitation therapy following major lower limb amputation at the Glenrose Rehabilitation Hospital. During the nine-month assessment period, 18 of 58 patients in the amputee unit experienced a fall, of which 17% resulted in a moderate injury. The majority of falls occurred during patients' use of a wheelchair (14 of 18) and involved poor balance (nine of 14). Patient wheelchair self-transfers accounted for 71% (10 of 14) of the falls, while sitting in the wheelchair and reaching represented 29/ (four of 14). The hospital's rehabilitation program teaches patient safety including using assistive devices such as wheelchairs but did not include a comprehensive graded learning path to monitor patients' ongoing risk for falls. Based upon the data collected, an intervention program was initiated to improve patient safety and reduce the number of falls. The multidisciplinary program encompassed aspects ranging from an environmental assessment of the patients' room to medication management, continuous patient wheelchair skills training and alteration of the care plan. The effectiveness of the intervention program was assessed through a series of interviews and questionnaires administered to medical personnel. This article presents the preliminary data collected during the first three months of the six-month study. Overall, satisfaction has significantly improved as a direct result of the intervention program. The article provides evidence-based interventions that improve safety for a subset of in-patients known to be susceptible to falls when using wheelchairs. Other in-patient groups will also benefit from these findings as many are universally applicable.

Alanine aminotransferase catalyses the breakdown of alanine after hypoxia in Arabidopsis thaliana.

Alanine aminotransferase (AlaAT) catalyses the reversible transfer of an amino group from glutamate to pyruvate to form 2-oxoglutarate and alanine. The regulation of AlaAT in several plant species has been studied in response to low-oxygen stress, light and nitrogen application. In this study, induction of Arabidopsis AlaAT1 and AlaAT2 during hypoxia was observed at the transcriptional level, and an increase in enzyme activity was detected in hypoxically treated roots. In addition, the tissue-specific expression of AlaAT1 and AlaAT2 was analysed using promoter:GUS fusions. The GUS staining patterns indicated that both AlaAT genes are expressed predominantly in vascular tissues. We manipulated AlaAT expression to determine the relative importance of this enzyme in low-oxygen stress tolerance and nitrogen metabolism. This was done by analysing T-DNA mutants and over-expressing barley AlaAT in Arabidopsis. The AlaAT1 knockout mutant (alaat1-1) showed a dramatic reduction in AlaAT activity, suggesting that AlaAT1 is the major AlaAT isozyme in Arabidopsis. Over-expression of barley AlaAT significantly increased the AlaAT activity in the transgenic plants. These plants were analysed for metabolic changes over a period of hypoxic stress and during their subsequent recovery. The results showed that alaat1-1 plants accumulate more alanine than wild-type plants during the early phase of hypoxia, and the decline in accumulated alanine was delayed in the alaat1-1 line during the post-hypoxia recovery period. When alanine was supplied as the nitrogen source, alaat1-1 plants utilized alanine less efficiently than wild-type plants did. These results indicate that the primary role of AlaAT1 is to break down alanine when it is in excess. Therefore, AlaAT appears to be crucial for the rapid conversion of alanine to pyruvate during recovery from low-oxygen stress.