Period Poverty from a Public Health and Legislative Perspective.

Period poverty is a global issue that needs to be addressed as a public health crisis. It is directly related to Sustainable Health Goals three, four, five, six, and eight. Period poverty adversely affects the health of anyone capable of menstruating, which is nearly half of the world population, at the physiological, emotional, and psychosocial level. Biases, cultural beliefs, ethical reproductive justice issues, social stigma, and systemic factors contribute to period poverty. Every month, certain menstruators are disproportionately impacted by period poverty and struggle to access basic hygienic necessities. Important stakeholders include not only the individual who experiences menses but also educators and school systems, healthcare professionals, policymakers, public health officials, and researchers. Everyone has a role in addressing period poverty by voting for officials that proactively support legislation, policy, and programs at all levels to effectively advocate for menstrual equity and address barriers contributing to period poverty. This includes policies that increase access to menstrual hygiene products, safe menstrual management methods, and reproductive and women's health education. Programs globally that focus on capacity building and sustainability strategies can be used as models to reduce period poverty, thereby fostering a sense of empowerment and menstruators' sense of autonomy, dignity, and equality.

The Relationship Between Yoga Practice Dosage and Perceived Stress, Anxiety, and Self-reported Health Among Breast Cancer Survivors Who Practice Yoga.

The aim of this anonymous online study was to explore the yoga practice of breast cancer survivors to determine if yoga dosage (frequency and duration of practice) was related to stress, anxiety, and self-reported health in female survivors. Participants were recruited from online breast cancer support groups during a 3-month period (June-September 2019). Demographic information, stage and treatment of breast cancer, and frequency of yoga participation, including a home yoga practice were reported. Measures include the Perceived Stress Scale, State-Trait Anxiety Inventory, and self-reported health. Cumulative yoga dosage was calculated. Thirty-five women participated (mean age = 55 years) and were divided into low and high yoga dosage groups based on the sample distribution. Low dosage of yoga was operationally defined as a cumulative dosage that fell within the lowest quartile (≤25%). Findings indicated no difference between the low-dosage group compared with the high-dosage group for perceived stress and self-reported health; but the high dosage yoga group had lower state anxiety scores (P < .05). All participants reported good self-reported health. These findings contribute to our knowledge of the psychosocial aspects of breast cancer survivorship and raise questions for further research quantifying the therapeutic dosing of yoga practice.

A pharmacist's unique opportunity within a multidisciplinary team to reduce drug-related problems for older adults in an intermediate care setting.

BACKGROUND: There is a paucity of research describing the pharmacist's role in the multidisciplinary care of older adults in the intermediate care setting. OBJECTIVE: To determine the types of drug-related problems (DRPs) in older patients in this setting, to evaluate the implementation rate of pharmacist recommendations and the factors affecting implementation, and to assess the clinical significance of these recommendations. METHODS: Data were collected over a 12-week period on one pharmacist's recommendations to reduce clinically relevant DRPs identified during medication reconciliation and review for all patients ≥65 years admitted to an intermediate care unit. The clinical significance of the recommendations was judged by four independent assessors using a validated tool. Statistical significance was predetermined as p < 0.05. RESULTS: Of 494 clinically relevant DRPs identified in 91 patients (mean age: 82 years), 406 recommendations were communicated to the medical team, and 89.2% were implemented. Overall, 48.5% were communicated verbally, but no difference was found between the implementation rates of verbal and written recommendations (87.8% versus 90.4%; p = 0.4). Medication reconciliation recommendations were implemented more commonly than those regarding medication review (96.5% versus 79.5%; p < 0.0001). Recommendations judged to be of 'moderate significance' (66.8% of total) were implemented more often than those of 'minor significance' (93.2% versus 81.6%; p < 0.001). The consultant was provided with a significantly higher proportion of recommendations of 'moderate significance' when compared to the junior doctor (79.6% versus 63.3%; p = 0.02), but implemented significantly fewer recommendations (69.4% versus 91.9%; p < 0.0001). CONCLUSION: The high implementation rate in this study shows the importance of pharmacist involvement to reduce DRPs in the multidisciplinary care of older adults in an intermediate care unit. Future research should focus on investigating the impact of pharmacist interventions on older patient outcomes and the associated cost-effectiveness in this setting.

Sustained Clinical Remission With Vedolizumab in Patients With Moderate-to-Severe Ulcerative Colitis.

BACKGROUND: Sustaining clinical remission is an important treatment goal in moderate-to-severe UC. This post hoc exploratory analysis assessed the long-term efficacy of vedolizumab in the subset of patients with UC in the GEMINI 1 study who were in clinical remission by week 14 after 3 induction doses, administered at weeks 0, 2, and 6. METHODS: Sustained clinical remission (primary endpoint) was evaluated using 2 definitions: (1) a partial Mayo Score (pMS) of ≤2 with no subscore >1 and (2) a rectal bleeding subscore (RBS) of 0 throughout weeks 14, 26, 38, and 52. RESULTS: The proportion of patients in clinical remission at week 14 was significantly higher in patients receiving vedolizumab (n = 620) compared with placebo (n = 149) (pMS: 32.7% vs 20.1% [percentage-point difference (∆) 12.6%; 95% confidence interval [CI], 5.2-20.0]; RBS: 47.3% vs 28.9% [∆18.4%; 95% CI, 10.1-26.7]). Of patients in clinical remission at week 14, a significantly higher proportion of vedolizumab-treated patients achieved sustained clinical remission compared with placebo (pMS: 66.5% vs 26.7%; ∆39.8%; 95% CI, 22.7-56.9; RBS: 56.7% vs 20.9%; ∆35.7%; 95% CI, 22.3-49.1). Findings were consistent in tumor necrosis factor (TNF) antagonist-naive and antagonist-failure patients. CONCLUSION: Compared with placebo, 35%-40% more patients receiving a full induction course of vedolizumab had sustained clinical remission after 52 weeks of therapy. This result was observed irrespective of TNF antagonist treatment history. Clinical remission at week 14 may therefore be a predictor for sustained clinical remission with vedolizumab.

Incidence of Arthritis/Arthralgia in Inflammatory Bowel Disease with Long-term Vedolizumab Treatment: Post Hoc Analyses of the GEMINI Trials.

BACKGROUND AND AIMS: Extraintestinal manifestations [EIMs] such as arthritis/arthralgia are common in inflammatory bowel disease. We performed post hoc analyses of data from the GEMINI studies to evaluate the effect of vedolizumab, a gut-selective anti-trafficking agent, on arthritis/arthralgia. METHODS: Sustained resolution of baseline arthritis/arthralgia, worsening of baseline arthritis/arthralgia, the occurrence of new arthritis/arthralgia, and the composite of new/worsening arthritis/arthralgia were evaluated. Cox modelling was used for time-to-event analysis. The influence of corticosteroid-tapering was also investigated. RESULTS: In Crohn's disease [CD] patients, vedolizumab was significantly less likely than placebo to be associated with new/worsening arthritis/arthralgia (hazard ratio [HR], 0.63; 95% confidence interval [CI], 0.44-0.89). Similar incidences of sustained resolution of arthritis/arthralgia occurred with vedolizumab and placebo. In CD patients on corticosteroids at baseline, a decrease in corticosteroid dose increased the risk of new/worsening arthritis/arthralgia (odds ratio [OR], 7.49; 95% CI, 3.50-15.97) regardless of treatment; and in those achieving corticosteroid-free status, arthritis/arthralgia was less likely with vedolizumab than with placebo [HR, 0.14; 95% CI, 0.05-0.35]. In ulcerative colitis [UC] patients, vedolizumab and placebo showed a similar incidence of new/worsening of arthritis/arthralgia. In UC patients on corticosteroid at baseline, arthritis/arthralgia was more likely in those achieving corticosteroid-free status than in those continuing corticosteroids (HR 2.63 [95% CI 1.13-6.11]); and in those achieving corticosteroid-free status, the incidence of arthritis/arthralgia was similar with vedolizumab and placebo. CONCLUSIONS: Vedolizumab therapy was associated with a reduced likelihood of new/worsening arthritis/arthralgia in CD and no increased incidence of these events in UC. STUDIES INCLUDED [CLINCIALTRIALS.GOV, NUMBER]: GEMINI 1 [NCT00783718]; GEMINI 2 [NCT00783692]; GEMINI 3 [NCT01224171].

Gut-Selective Integrin-Targeted Therapies for Inflammatory Bowel Disease.

Integrins are cell surface receptors with bidirectional signalling capabilities that can bind to adhesion molecules in order to mediate homing of leukocytes to peripheral tissues. Gut-selective leukocyte homing is facilitated by interactions between α4ß7 and its ligand, mucosal addressin cellular adhesion molecule-1 [MAdCAM-1], while retention of lymphocytes in mucosal tissues is mediated by αEß7 binding to its ligand E-cadherin. Therapies targeting gut-selective trafficking have shown efficacy in inflammatory bowel disease [IBD], confirming the importance of leukocyte trafficking in disease pathobiology. This review will provide an overview of integrin structure, function and signalling, and highlight the role that these molecules play in leukocyte homing and retention. Anti-integrin therapeutics, including gut-selective antibodies against the ß7 integrin subunit [etrolizumab] and the α4ß7 integrin heterodimer [vedolizumab and abrilumab], and the non-gut selective anti-α4 integrin [natalizumab], will be discussed, as well as novel targeting approaches using small molecules.

Pharmacokinetic and Pharmacodynamic Modeling of Serum Etrolizumab and Circulating ß7 Receptor Occupancy in Patients With Ulcerative Colitis.

Etrolizumab, a humanized monoclonal antibody, specifically binds to the ß7 subunit of the heterodimeric integrins α4ß7 and αEß7. Pharmacokinetic (PK) and pharmacodynamic (PD) data were collected from an etrolizumab phase 1 trial in patients with moderate to severe ulcerative colitis (UC). We developed a mechanism-based model to simultaneously describe the kinetics of serum etrolizumab concentration and free ß7 receptors on circulating intestinal-homing CD4+ T lymphocytes. Included in the analysis were 38 phase 1 UC patients who received single or 3 monthly doses of etrolizumab intravenously or subcutaneously across a dose range of 0.3 to 10 mg/kg. A quasi-steady-state target-mediated drug disposition model was developed to describe the dynamic interaction between serum etrolizumab concentration and free ß7 receptors on intestinal-homing CD4+ T lymphocytes in UC patients. The time profiles of serum etrolizumab and absolute counts of ß7+ lymphocytes (expressed as percentage of baseline level) were well described by the quasi-steady-state target-mediated drug disposition model. The model was able to characterize the maximum drug occupancy of ß7 receptors on intestinal-homing CD4+ T lymphocytes and the concentration-dependent duration of occupancy. The 90% effective concentration for etrolizumab to saturate the ß7 receptors on intestinal homing CD4+ T cells was 1.3 µg/mL. PK and PD profiles predicted by the model were consistent with observations from a subsequent phase 2 study. In conclusion, an integrated PK/PD model developed in this analysis reasonably described serum etrolizumab PK profiles and the relationship between PK and PD (free ß7 receptors on circulating intestinal-homing CD4+ T lymphocytes) in UC patients.

Optimising mindfulness-based stress reduction for people with multiple sclerosis.

Objectives To gather views from patients with multiple sclerosis after completing a standard eight-week mindfulness-based stress reduction course and optimise and test a modified version as required. Methods Two successive groups of 25 multiple sclerosis patients received mindfulness-based stress reduction in a wait-list randomised controlled trial. Seventeen participants and two mindfulness-based stress reduction instructors were individually interviewed after the first (standard) course and 16 participants and the same two instructors were interviewed following the second (optimised) course. Interviews were analysed using a thematic approach. Results Mindfulness-based stress reduction was well received in both groups, with participants describing a beneficial shift in awareness. An initial (at times unpleasant) increase in awareness of disability was generally followed by greater acceptance and self-compassion. Other benefits reported included improved relationships, walking and sleep, with less stress and pain. Mindful-movement and mindful walking were problematic in group 1. This component of mindfulness-based stress reduction was simplified in group 2. A pre-course orientation session was introduced, and some organisational changes made based on feedback from group 1. Feedback from group 2 was positive in all these areas. Discussion Mindfulness-based stress reduction appears beneficial to people with multiple sclerosis, albeit mindful-movement required some modification. Contextual and organisational issues also appear important in this population.

What's the Buzz: Tell Me What's Happening in Breast Cancer Screening.

Many controversies have come to light related to breast cancer screening recommendations for average- and high-risk populations. This manuscript focuses on factors to consider when coordinating and conducting breast cancer screening programs in an average or "healthy women" population. As presented at the 2016 ONS Congress, a brief comparison of current screening recommendations among various organizations for early detection of breast cancer is provided. Lessons learned regarding key components of successful screening programs such as being patient focused, accessible, and sustainable are shared. Practice implications such as gaining confidence in providing individualized patient education, encouraging every woman to discuss her risk of breast cancer with her health-care provider, advocating for patients needs and being involved in or aware of clinical and translational research on the efficacy of the clinical breast examination and screening services are critical roles for nurses and advanced practice nurse providers.

αEß7 Integrin Identifies Subsets of Pro-Inflammatory Colonic CD4+ T Lymphocytes in Ulcerative Colitis.

BACKGROUND AND AIMS: The αEß7 integrin is crucial for retention of T lymphocytes at mucosal surfaces through its interaction with E-cadherin. Pathogenic or protective functions of these cells during human intestinal inflammation, such as ulcerative colitis [UC], have not previously been defined, with understanding largely derived from animal model data. Defining this phenotype in human samples is important for understanding UC pathogenesis and is of translational importance for therapeutic targeting of αEß7-E-cadherin interactions. METHODS: αEß7+ and αEß7- colonic T cell localization, inflammatory cytokine production and expression of regulatory T cell-associated markers were evaluated in cohorts of control subjects and patients with active UC by immunohistochemistry, flow cytometry and real-time PCR of FACS-purified cell populations. RESULTS: CD4+αEß7+ T lymphocytes from both healthy controls and UC patients had lower expression of regulatory T cell-associated genes, including FOXP3, IL-10, CTLA-4 and ICOS in comparison with CD4+αEß7- T lymphocytes. In UC, CD4+αEß7+ lymphocytes expressed higher levels of IFNγ and TNFα in comparison with CD4+αEß7- lymphocytes. Additionally the CD4+αEß7+ subset was enriched for Th17 cells and the recently described Th17/Th1 subset co-expressing both IL-17A and IFNγ, both of which were found at higher frequencies in UC compared to control. CONCLUSION: αEß7 integrin expression on human colonic CD4+ T cells was associated with increased production of pro-inflammatory Th1, Th17 and Th17/Th1 cytokines, with reduced expression of regulatory T cell-associated markers. These data suggest colonic CD4+αEß7+ T cells are pro-inflammatory and may play a role in UC pathobiology.

Impact of team-versus ward-aligned clinical pharmacy on unintentional medication discrepancies at admission.

Background Medication reconciliation at admission to hospital reduces the prevalence of medication errors. Strategies are needed to ensure timely and efficient delivery of this service. Objective To investigate the effect of aligning clinical pharmacy services with consultant teams, by pharmacists attending post-admission ward rounds, in comparison to a ward-based service, on prevalence of unintentional unresolved discrepancies 48 h into admission. Setting A 243-bed public university teaching hospital in Ireland. Method A prospective, uncontrolled before-after observational study. A gold standard preadmission medication list was completed for each patient and compared with the patient's admission medication prescription and discrepancies were noted. Unresolved discrepancies were examined at 48 h after admission to determine if they were intentional or unintentional. Main outcome measured Number of patients with one or more unintentional, unresolved discrepancy 48 h into admission. Results Data were collected for 140 patients, of whom 73.5% were over 65 years of age. There were no differences between before (ward-aligned) and after (team-aligned) groups regarding age, number of medications or comorbidities. There was a statistically significant reduction in the prevalence of unintentional, unresolved discrepancy(s) per patient (67.3 vs. 27.3%, p < 0.001) and per medication (13.7 vs. 4.1%, p < 0.001) between the groups, favouring the team-based service. The effect remained statistically significant having adjusted for patient age, number of medications and comorbidities (adjusted odds ratio 4.9, 95% confidence interval 2.3-10.6). Conclusion A consultant team-based clinical pharmacy service contributed positively to medication reconciliation at admission, reducing the prevalence of unintentional, unresolved discrepancy(s) present 48 h after admission.

Discovery of Biomarkers of Response in Early Drug Development.

Ulcerative colitis and Crohn's disease have traditionally been managed by incrementally stepping up within a hierarchy of therapeutic classes consequent to failing a given therapeutic─necessitated by the notion that any type of therapeutic will only induce clinical response and remission in a fraction of, but not all, patients. Hence, the selection of therapies approximates stage of disease rather than patient-specific characteristics that would allow selection of a specific mechanism of action for therapeutic intervention. Development of prognostic biomarkers [to identify patients with more aggressive disease and a worse prognosis], as well as predictive biomarkers [to predict response or non-response to a particular therapy], has been identified as a key requirement for attainment of better overall response rates or to improve the response of the most severely ill patient subgroup. Since the state of biomarker development is early and the process in inflammatory bowel disease appears more complex than in other therapeutic areas such as oncology, profiling of potential biomarkers across broad populations of undifferentiated patients will be important in refining current hypotheses and progressing their study and validation.

Agreement Between Rectosigmoidoscopy and Colonoscopy Analyses of Disease Activity and Healing in Patients With Ulcerative Colitis.

BACKGROUND & AIMS: Endoscopy limited to the rectosigmoid colon is the standard technique used to measure endoscopic healing in ulcerative colitis (UC) clinical trials. We evaluated whether rectosigmoidoscopy adequately measures UC activity in the more proximal colon. METHODS: We analyzed data from a phase 2, placebo-controlled study that evaluated the efficacy and safety of etrolizumab in patients with moderate to severely active UC who had not responded to standard therapy. Central readers determined Mayo Clinic endoscopic subscores (MCSe) and ulcerative colitis endoscopic index of severity (UCEIS) scores from the rectosigmoid and proximal colon in videos of 331 examinations performed at baseline, week 6, and week 10. Rates of endoscopic healing (MCSe ≤ 1, MCSe = 0) and scores from rectosigmoidoscopy and colonoscopy analyses were compared among 239 examinations with endoscopic assessment proximal to the rectosigmoid colon. RESULTS: There was a high degree of correlation between findings from rectosigmoidoscopy vs colonoscopy in assessment of disease activity based on MCSe of 2 or higher (r = 0.84) or MCSe of 1 or higher (r = 0.96), or the UCEIS score (r = 0.92). In 230 of 239 videos, findings from rectosigmoidoscopy agreed with those from colonoscopy in the detection of active disease (MCSe ≥ 2; n = 205) or healing (MCSe ≤ 1; n = 25). In 9 videos (2 taken at baseline, 7 taken after treatment), colonoscopy found proximal disease activity not detected by rectosigmoidoscopy. Post-treatment discordance was more frequent in the placebo group, affecting assessment of efficacy at week 10. When endoscopic healing was defined as MCSe of 0, there were discordant findings from only 1 video. CONCLUSIONS: There is a high degree of correlation in assessments of UC activity made by rectosigmoidoscopy vs colonoscopy. For detection of endoscopic healing (MCSe ≤ 1), colonoscopy found persistent proximal lesions in the placebo group, which affected efficacy analyses. When endoscopic healing was defined as MCSe of 0, the concordance between rectosigmoidoscopy and colonoscopy was nearly perfect.

Association Between Response to Etrolizumab and Expression of Integrin αE and Granzyme A in Colon Biopsies of Patients With Ulcerative Colitis.

BACKGROUND & AIMS: Etrolizumab is a humanized monoclonal antibody against the ß7 integrin subunit that has shown efficacy vs placebo in patients with moderate to severely active ulcerative colitis (UC). Patients with colon tissues that expressed high levels of the integrin αE gene (ITGAE) appeared to have the best response. We compared differences in colonic expression of ITGAE and other genes between patients who achieved clinical remission with etrolizumab vs those who did. METHODS: We performed a retrospective analysis of data collected from 110 patients with UC who participated in a phase 2 placebo-controlled trial of etrolizumab, as well as from 21 patients with UC or without inflammatory bowel disease (controls) enrolled in an observational study at a separate site. Colon biopsies were collected from patients in both studies and analyzed by immunohistochemistry and gene expression profiling. Mononuclear cells were isolated and analyzed by flow cytometry. We identified biomarkers associated with response to etrolizumab. In the placebo-controlled trial, clinical remission was defined as total Mayo Clinic Score ≤2, with no individual subscore >1, and mucosal healing was defined as endoscopic score ≤1. RESULTS: Colon tissues collected at baseline from patients who had a clinical response to etrolizumab expressed higher levels of T-cell-associated genes than patients who did not respond (P < .05). Colonic CD4(+) integrin αE(+) cells from patients with UC expressed higher levels of granzyme A messenger RNA (GZMA mRNA) than CD4(+) αE(-) cells (P < .0001); granzyme A and integrin αE protein were detected in the same cells. Of patients receiving 100 mg etrolizumab, a higher proportion of those with high levels of GZMA mRNA (41%) or ITGAE mRNA (38%) than those with low levels of GZMA (6%) or ITGAE mRNA (13%) achieved clinical remission (P < .05) and mucosal healing (41% GZMA(high) vs 19% GZMA(low) and 44% ITGAE(high) vs 19% ITGAE(low)). Compared with ITGAE(low) and GZMA(low) patients, patients with ITGAE(high) and GZMA(high) had higher baseline numbers of epithelial crypt-associated integrin αE(+) cells (P < .01 for both), but a smaller number of crypt-associated integrin αE(+) cells after etrolizumab treatment (P < .05 for both). After 10 weeks of etrolizumab treatment, expression of genes associated with T-cell activation and genes encoding inflammatory cytokines decreased by 40%-80% from baseline (P < .05) in patients with colon tissues expressing high levels of GZMA at baseline. CONCLUSIONS: Levels of GZMA and ITGAE mRNAs in colon tissues can identify patients with UC who are most likely to benefit from etrolizumab; expression levels decrease with etrolizumab administration in biomarker(high) patients. Larger, prospective studies of markers are needed to assess their clinical value.

Lymphatic Filariasis in Children in Haiti.

Using available evidence and astute assessment skills, nurses and advanced practice nurses, as members of an inter-professional team, were able to assess, diagnose, and initiate treatment for a child with lymphatic filariasis within a global health practice setting. The lessons learned during health outreach trips to an underserved commune of Port-au-Prince, Haiti can promote an understanding of appropriate nursing practice related to this parasitic infection. They can also assist nursing students, nurse practitioner students, and faculties as members of a medical outreach team to promote sustainability which is a benchmark of nursing leadership in global health.

Etrolizumab as induction therapy for ulcerative colitis: a randomised, controlled, phase 2 trial.

BACKGROUND: Etrolizumab is a humanised monoclonal antibody that selectively binds the ß7 subunit of the heterodimeric integrins α4ß7 and αEß7. We aimed to assess etrolizumab in patients with moderately-to-severely active ulcerative colitis. METHODS: In this double-blind, placebo-controlled, randomised, phase 2 study, patients with moderately-to-severely active ulcerative colitis who had not responded to conventional therapy were recruited from 40 referral centres in 11 countries. Eligible patients (aged 18-75 years; Mayo Clinic Score [MCS] of 5 of higher [or ≥6 in USA]; and disease extending 25 cm or more from anal verge) were randomised (1:1:1) to one of two dose levels of subcutaneous etrolizumab (100 mg at weeks 0, 4, and 8, with placebo at week 2; or 420 mg loading dose [LD] at week 0 followed by 300 mg at weeks 2, 4, and 8), or matching placebo. The primary endpoint was clinical remission at week 10, defined as MCS of 2 or less (with no individual subscore of >1), analysed in the modified intention-to-treat population (mITT; all randomly assigned patients who had received at least one dose of study drug, had at least one post-baseline disease-activity assessment, and had a centrally read screening endoscopic subscore of ≥2). This study is registered with ClinicalTrials.gov, number NCT01336465. FINDINGS: Between Sept 2, 2011, and July 11, 2012, 124 patients were randomly assigned, of whom five had a endoscopic subscore of 0 or 1 and were excluded from the mITT population, leaving 39 patients in the etrolizumab 100 mg group, 39 in the etrolizumab 300 mg plus LD group, and 41 in the placebo group for the primary analyses. No patients in the placebo group had clinical remission at week 10, compared with eight (21% [95% CI 7-36]) patients in the etrolizumab 100 mg group (p=0·0040) and four (10% [0·2-24]) patients in the 300 mg plus LD group (p=0·048). Adverse events occurred in 25 (61%) of 41 patients in the etrolizumab 100 mg group (five [12%] of which were regarded as serious), 19 (48%) of 40 patients in the etrolizumab 300 mg plus LD group (two [5%] serious), and 31 (72%) of 43 patients in the placebo group (five [12%] serious). INTERPRETATION: Etrolizumab was more likely to lead to clinical remission at week 10 than was placebo. Therefore, blockade of both α4ß7 and αEß7 might provide a unique therapeutic approach for the treatment of ulcerative colitis, and phase 3 studies have been planned. FUNDING: Genentech.

Mindfulness based interventions in multiple sclerosis--a systematic review.

BACKGROUND: Multiple sclerosis (MS) is a stressful condition; depression, anxiety, pain and fatigue are all common problems. Mindfulness based interventions (MBIs) mitigate stress and prevent relapse in depression and are increasingly being used in healthcare. However, there are currently no systematic reviews of MBIs in people with MS. This review aims to evaluate the effectiveness of MBIs in people with MS. METHODS: Systematic searches were carried out in seven major databases, using both subject headings and key words. Papers were screened, data extracted, quality appraised, and analysed by two reviewers independently, using predefined criteria. Study quality was assessed using the Cochrane Collaboration risk of bias tool. Perceived stress was the primary outcome. Secondary outcomes include mental health, physical health, quality of life, and health service utilisation. Statistical meta-analysis was not possible. Disagreements were adjudicated by a third party reviewer. RESULTS: Three studies (n = 183 participants) were included in the final analysis. The studies were undertaken in Wales (n = 16, randomised controlled trial - (RCT)), Switzerland (n = 150, RCT), and the United States (n = 17, controlled trial). 146 (80%) participants were female; mean age (SD) was 48.6 (9.4) years. Relapsing remitting MS was the main diagnostic category (n = 123, 67%); 43 (26%) had secondary progressive disease; and the remainder were unspecified. MBIs lasted 6-8 weeks; attrition rates were variable (5-43%); all employed pre- post- measures; two had longer follow up; one at 3, and one at 6 months. Socio-economic status of participants was not made explicit; health service utilisation and costs were not reported. No study reported on perceived stress. All studies reported quality of life (QOL), mental health (anxiety and depression), physical (fatigue, standing balance, pain), and psychosocial measures. Statistically significant beneficial effects relating to QOL, mental health, and selected physical health measures were sustained at 3- and 6- month follow up. CONCLUSION: From the limited data available, MBIs may benefit some MS patients in terms of QOL, mental health, and some physical health measures. Further studies are needed to clarify how MBIs might best serve the MS population.

EMerging BiomARKers in Inflammatory Bowel Disease (EMBARK) study identifies fecal calprotectin, serum MMP9, and serum IL-22 as a novel combination of biomarkers for Crohn's disease activity: role of cross-sectional imaging.

OBJECTIVES: In Crohn's disease (CD), clinical symptoms correspond poorly to inflammatory disease activity. Biomarkers reflective of mucosal and bowel wall inflammation would be useful to monitor disease activity. The EMBARK study evaluated disease activity in patients with ulcerative colitis (UC) and CD, and used endoscopy with or without cross-sectional imaging for biomarker discovery. METHODS: UC (n=107) and CD (n=157) patients were characterized and underwent ileocolonoscopy (ICO). A subset of CD patients (n=66) also underwent computed tomography enterography (CTE). ICO and CTE were scored by a gastroenterologist and radiologist who incorporated findings of inflammation into a single score (ICO-CTE) for patients that underwent both procedures. Serum and fecal biomarkers were evaluated for association with the Mayo Clinic endoscopy score in UC patients and with ICO alone or ICO-CTE in CD patients. Individual biomarkers with a moderate degree of correlation (P≤0.3) were evaluated using multivariate analysis with model selection using a stepwise procedure. RESULTS: In UC, ordinal logistic regression using Mayo Clinic endoscopy subscore selected the combination of fecal calprotectin and serum matrix metalloproteinase 9 (MMP9; pseudo R(2)=0.353). In CD, we found that use of the ICO-CTE increased specificity of known biomarkers. Using ICO-CTE as the dependent variable for biomarker discovery, the selected biomarkers were the combination of fecal calprotectin, serum MMP9, and serum IL-22 (r=0.699). CONCLUSIONS: Incorporation of both ICO and CTE into a single measure increased biomarker performance in CD. Combinations of fecal calprotectin and serum MMP9 for UC, and combinations of fecal calprotectin, serum MMP9, and serum interleukin-22 in CD, demonstrated the strongest association with imaging/endoscopy-defined inflammation.

A randomised phase I study of etrolizumab (rhuMAb ß7) in moderate to severe ulcerative colitis.

OBJECTIVE: Etrolizumab (rhuMAb ß7, anti-ß7, PRO145223) is a humanised monoclonal antibody targeting the ß7 subunit of the heterodimeric integrins α4ß7 and αEß7, which are implicated in leucocyte migration and retention in ulcerative colitis (UC). This randomised phase I study evaluated the safety and pharmacology of etrolizumab in patients with moderate to severe UC. DESIGN: In the single ascending dose (SAD) stage, etrolizumab (0.3, 1.0, 3.0, 10 mg/kg intravenous, 3.0 mg/kg subcutaneous (SC) or placebo) was administered 4:1 (n=25) in each cohort. In the multiple dose (MD) stage, new patients received monthly etrolizumab (0.5 mg/kg SC (n=4), 1.5 mg/kg SC (n=5), 3.0 mg/kg SC (n=4), 4.0 mg/kg intravenous (n=5)) or placebo (n=5). The pharmacokinetics was studied and Mayo Clinic Score evaluated at baseline, day 29 (SAD), and days 43 and 71 (MD). RESULTS: In the SAD stage, there were no dose limiting toxicities, infusion or injection site reactions. Two impaired wound healing serious adverse events occurred in two patients receiving etrolizumab. In the MD stage, there were no dose limiting toxicities, and no infusion or injection site reactions. Headache was the most common adverse event, occurring more often in etrolizumab patients. Antietrolizumab antibodies were detected in two subjects. The duration of ß7 receptor full occupancy was dose related. A clinical response was observed in 12/18 patients, and clinical remission in 3/18 patients treated with etrolizumab in the MD stage, compared with 4/5 and 1/5 placebo patients, respectively. CONCLUSION: Etrolizumab is well tolerated in moderate to severe UC. Further investigation is warranted.

Factors associated with why African-American women from one urban county use mammography services less.

A two-group comparison pilot study was conducted with 60 (N = 60) U.S. born African-American women to determine the factors associated with decreased utilization of mammography among women who have access to mammography services, yet choose not to utilize them. Findings from the study suggest that African-American acculturation and Health Temporal Orientation were significantly associated with mammography utilization (p = 0.01). There was no significant relationship between other cultural beliefs, health-care avoidance, or sociodemographic status indicators. Six content areas also emerged from a focus group discussion associated with barriers/factors related to mammography utilization. Findings from this study also suggest that further research and outreach is needed to address the development of tailored interventions to increase the rate of mammography utilization and reduce the incidence and mortality related to breast cancer in African-American women.