Vedolizumab exposure in pregnancy: outcomes from clinical studies in inflammatory bowel disease.

BACKGROUND: Vedolizumab is a gut-selective immunoglobulin G1 monoclonal antibody to α4 ß7 integrin for the treatment of Crohn's disease (CD) and ulcerative colitis (UC). Prospective clinical studies of vedolizumab in pregnancy have not been conducted; therefore, existing safety data of vedolizumab in pregnancy were examined. AIM: To assess pregnancy outcomes in females and partners of males who received vedolizumab. METHODS: All pregnancy data collected during the clinical programme (from 14 May 2007 to 27 June 2013) and in the post-marketing setting (to 19 November 2015) were analysed. RESULTS: Across six studies, there were 27 pregnancies in female participants and 19 pregnancies in partners of male participants. Among 24 vedolizumab-treated females (23 with CD/UC, one healthy volunteer), there were 11 live births, five elective terminations, four spontaneous abortions and four undocumented outcomes. A congenital corpus callosum agenesis anomaly was reported in one live birth from a healthy volunteer with extensive obstetric history exposed to single-dose vedolizumab 79 days before estimated conception. Of 19 pregnancies in partners of male participants, there were 11 live births, two spontaneous abortions, three elective terminations and three undocumented outcomes. Post-marketing reports recorded 81 pregnancies, resulting in four live births, 11 spontaneous abortions and 66 pregnancies that were on-going or reported undocumented outcomes. CONCLUSIONS: Initial analysis, limited by sample size and follow-up, identified no new safety concerns for pregnancy outcomes in females directly or indirectly exposed to vedolizumab. However, vedolizumab should be used during pregnancy only if the benefits to the mother outweigh the risks to the mother/unborn child.

Effects of vedolizumab on health-related quality of life in patients with ulcerative colitis: results from the randomised GEMINI 1 trial.

BACKGROUND: Health-related quality of life (HRQL) is often diminished in patients with ulcerative colitis. AIM: To evaluate the effects of vedolizumab on HRQL in patients with ulcerative colitis. METHODS: Using maintenance phase data from the GEMINI 1 study, an analysis of covariance model was used to calculate mean differences between the vedolizumab and placebo groups in changes from baseline to week 52 for 3 HRQL instruments: The Inflammatory Bowel Disease Questionnaire (IBDQ), 36-Item Short Form Health Survey (SF-36), and EQ-5D. Proportions of patients meeting minimal clinically important difference (MCID) thresholds for changes on these instruments were compared between treatment groups for the overall population and for clinically important subgroups. Concordance between clinical remission and remission defined using IBDQ scores was examined. RESULTS: Compared with placebo-treated patients, vedolizumab-treated patients had greater improvements (152-201%) in IBDQ, EQ-5D visual analogue scale (VAS), and EQ-5D utility scores. Greater proportions (6.9-19.9%) of vedolizumab-treated patients than placebo-treated patients met MCID thresholds for all the instruments. Vedolizumab-treated patients with lower baseline disease activity and those without prior tumour necrosis factor (TNF) antagonist failure had greater HRQL improvements. Among 127 patients with clinical remission based on complete Mayo Clinic scores, >80% also had IBDQ remission; >70% of the 150 patients with IBDQ remission demonstrated clinical remission. CONCLUSIONS: Vedolizumab therapy was associated with significant improvements in HRQL measures compared with placebo. Benefits were greater in patients with lower disease activity and no prior TNF antagonist failure.

Qualitative development of a patient-reported outcome symptom measure in diarrhea-predominant irritable bowel syndrome.

OBJECTIVES: Despite a documented clinical need, no patient reported outcome (PRO) symptom measure meeting current regulatory requirements for clinically relevant end points is available for the evaluation of treatment benefit in diarrhea-predominant IBS (IBS-D). METHODS: Patients (N=113) with IBS-D participated in five study phases: (1) eight concept elicitation focus groups (N=34), from which a 17-item IBS-D Daily Symptom Diary and four-item IBS-D Symptom Event Log (Diary and Event Log) were developed; (2) one-on-one cognitive interviews (N=11) to assess the instrument's comprehensiveness, understandability, appropriateness, and readability; (3) four data triangulation focus groups (N=32) to confirm the concepts elicited; (4) two hybrid (concept elicitation and cognitive interview) focus groups (N=16); and (5) two iterative sets of one-on-one cognitive interviews (N=20) to further clarify the symptoms of IBS-D and debrief a revised seven-item Diary and four-item Event Log. RESULTS: Of thirty-six concepts initially identified, 22 were excluded because they were not saturated, not clinically relevant, not critical symptoms of IBS-D, considered upper GI symptoms, or too broad or vaguely defined. The remaining concepts were diarrhea, immediate need (urgency), bloating/pressure, frequency of bowel movements, cramps, abdominal/stomach pain, gas, completely emptied bowels/incomplete evacuation, accidents, bubbling in intestines (bowel sounds), rectal burning, stool consistency, rectal spasm, and pain while wiping. The final instrument included a daily diary with separate items for abdominal and stomach pain and an event log with four items completed after each bowel movement as follows: (1) a record of the bowel movement/event and an assessment of (2) severity of immediacy of need/bowel urgency, (3) incomplete evacuation, and (4) stool consistency (evaluated using the newly developed Astellas Stool Form Scale). Based on rounds of interviews and clinical input, items considered secondary or nonspecific to IBS-D (rectal burning, bubbling in intestines, spasms, and pain while wiping) were excluded. CONCLUSIONS: The IBS-D Symptom Diary and Event Log represent a rigorously developed PRO instrument for the measurement of the IBS-D symptom experience from the perspective of the patient. Its content validity has been supported, and future work should evaluate the instrument's psychometric properties.

Risk of developing colorectal cancer and benign colorectal neoplasm in patients with chronic constipation.

BACKGROUND: Chronic constipation (CC) is a highly prevalent health problem, potentially associated with increased risk of colorectal cancer (CRCancer). AIM: To investigate the association between CC, its severity, and CRCancer by estimating the relative risk of developing CRCancer and benign colorectal neoplasm (BCN) among severity-stratified patients with and without CC. METHODS: Chronic constipation patients from a large retrospective US claims database were matched 1:3 with CC-free controls by demographic characteristics. CRCancer and BCN prevalence were measured over 1 year. In pre-index CRCancer- and BCN-free patients, incidence rate ratios (IRRs) of new CRCancer and BCN were calculated. Multivariate regression models adjusted for comorbidities and family history. CC patients' disease severity was rated based on CC-related resource use. IRRs for new CRCancer and BCN were estimated for CC severity groups and controls. RESULTS: Chronic constipation (N = 28,854) and CC-free (N = 86,562) patients had mean age 61.9 years; 66.7% were female. One-year CRCancer prevalence was 2.7% and 1.7%, and BCN prevalence was 24.8% and 11.9% for CC and CC-free patients, respectively. Adjusted IRRs between CC and CC-free patients were 1.59 [95% confidence interval (CI): 1.43-1.78] and 2.60 [95% CI: 1.51-2.70] for CRCancer and BCN, respectively. Patients with severe and very severe CC had significantly greater incidence of CRCancer and BCN. At ≥ 2 and ≥ 5 years of observation, CRCancer and BCN incidence remained consistently and significantly higher for CC patients. CONCLUSIONS: Patients with chronic constipation are associated with significantly higher prevalence and incidence of colorectal cancer and benign colorectal neoplasm than matched chronic constipation-free patients. These risks increase with the severity of chronic constipation.

Why study pain? A qualitative analysis of medical and nursing faculty and students' knowledge of and attitudes to cancer pain management.

Although effective means for pain management have long been available, cancer pain remains widely undertreated. Surveys of medical personnel have revealed knowledge deficits and attitudinal barriers to pain management, but have not determined why such attitudes persist and how they may be addressed in medical and nursing curricula. This paper presents findings from a qualitative study of the beliefs and attitudes toward pain and cancer pain management held by medical and nursing students and faculty who participated in the Cancer Education Module for the Management of Pain (CEMMP) project. Analysis centered on informants' prioritization and knowledge of pain and cancer pain management and on the meanings informants assigned to pain in a clinical context. Themes in prioritization included the importance of learning about pain versus cancer pain and the responsibility of primary care providers versus specialists for pain and cancer pain management. Themes in informants' knowledge of pain included knowledge deficits about medications and adjunct therapies and the presence of pain management in the curriculum, and the role of knowledgeable faculty members and mentors in the dissemination of information about pain management. Themes in the meanings informants' assigned to pain included opioidphobia, and the (inter-)subjectivity of pain. The discussion focuses in particular on tensions within the prioritization, knowledge and meanings of pain that must be resolved before students can be appropriately educated for optimal pain management.

The relation of family violence, employment status, welfare benefits, and alcohol drinking in the United States.

OBJECTIVE: To examine the contribution of employment status, welfare benefits, alcohol use, and other individual and contextual factors to physical aggression during marital conflict. METHODS: Logistic regression models were used to analyze panel data collected in the National Survey of Families and Households in 1987 and 1992. A total of 4,780 married or cohabiting persons reinterviewed in 1992 were included in the analysis. Domestic violence was defined as reporting that both partners were physically violent during arguments. RESULTS: Unemployed respondents are not at greater risk of family violence than employed respondents, after alcohol misuse, income, education, age, and other factors are controlled for; however, employed persons receiving welfare benefits are at significantly higher risk. Alcohol misuse, which remains a predictor of violence even after other factors are controlled for, increases the risk of family violence, and satisfaction with social support from family and friends is associated with its decrease. CONCLUSIONS: Alcohol misuse has an important effect on domestic violence, and the potential impact of welfare reform on domestic violence needs to be monitored.

Family violence, employment status, welfare benefits, and alcohol drinking in the United States: what is the relation?

OBJECTIVES: This study examined the contribution of employment status, welfare benefits, alcohol use, and other individual, and contextual factors to physical aggression during marital conflict. METHODS: Logistic regression models were used to analyse panel data collected in the National Survey of Families and Households in 1987 and 1992. A total of 4780 married or cohabiting persons re-interviewed in 1992 were included in the analysis. Domestic violence was defined as reporting that both partners were physically violent during arguments. RESULTS: It was found that non-employed respondents are not at greater risk of family violence in comparison with employed respondents, after controlling for alcohol misuse, income, education, age, and other factors; however, employed persons receiving welfare benefits are at significantly higher risk. Alcohol misuse, which remains a predictor of violence even after controlling for other factors, increases the risk of family violence while satisfaction with social support from family and friends decreases it. CONCLUSION: These results underscore the important effect of alcohol misuse on domestic violence, and the need to monitor the potential impact of welfare reform on domestic violence.

Using focus group methods to develop multicultural cancer pain education materials.

Methods to treat cancer pain effectively have existed for more than 2 decades. However, the effective treatment of cancer pain continues to elude many patients with cancer who suffer from poor management. Although efforts to address the problem of cancer pain in the United States have acknowledged the importance of patient education and advocacy, few endeavors, to date, have attended to the special needs of inner-city, low-literacy, or socioeconomically disadvantaged patients from minority cultural groups. From 1992 to 1995, the Boston Cancer Pain Education Program, funded by the National Cancer Institute and the American Cancer Society, worked collaboratively with community representatives using focus group methods to develop a culturally sensitive, linguistically appropriate cancer pain education booklet in 11 languages and for 11 ethnic groups. The booklet serves as a guide for patients and families and is to be used as a teaching tool by clinicians. The focus group approach was used to develop materials that would empower patients and families to more effectively participate in pain management when working with health care providers from cultures other than their own. Qualitative data analysis methods were used to analyze transcripts of taped focus group sessions. Themes emerged from the data regarding pain and its culturally competent management as well as the group process of booklet development.

Is hands-on experience more effective than didactic workshops in postgraduate cancer pain education?

BACKGROUND: This study examined the nurse outcomes of a cancer pain education program for nurses of patients from 11 different ethnic groups. METHODS: Four hundred ninety six home, hospital, and hospice nurses participated in a one-day workshop or two half-day workshops on cancer pain assessment and management. Of these, 116 were randomized to participate in a bedside-precepted visit with an oncology nurse specialist with pain specialization and a focus group to discuss attitudinal issues. Eighty-six nurses served as controls. Pre-, post- and one-year follow-up tests were administered. RESULTS: Attitudes, knowledge, and application skills significantly improved for workshop-only and enriched-model nurses relative to controls. CONCLUSION: For postgraduate nurses, daylong cancer pain education workshops were, in the group studied, as effective as hands-on experience in improving cancer pain knowledge and changing attitudes. Both the workshop-only and the enriched-model nurses relative to controls had significantly improved knowledge and changed attitudes towards optimal pain management.

Culture, pain, and culturally sensitive pain care.

One of the factors that can influence a person's perception of the pain experience is culture. With the large increase in the immigrant population in the United States, particularly immigrants coming from nontraditional regions such as Southeast Asia and Latin America, clinicians need to develop increased sensitivity to the influence of culture on health care beliefs and practices. To more effectively manage pain, clinicians need to conduct culturally sensitive pain assessments that elicit information concerning patients' and family members' beliefs about the pain experience. In addition, the patient's and family members' cultural beliefs and approaches toward traditional healing practices need to be incorporated into the pain management plan.

[Selenium therapy in colorectal tumors?]. / Selentherapie bei kolorektalen Tumoren?

BACKGROUND: Is the complementary supplementation of selenium useful in the therapy of colorectal cancer? PATIENTS AND METHODS: Fifty-three patients with primary colorectal cancer received a selenium treatment for 19 days in addition to a complete in-patient rehabilitation cure based on a behavioural approach. A comparative control group consisted of 41 patients. Measured factors were the selenium content in serum and whole blood, GSH-Px activity and TBARS in serum. Both the intake of selenium by nutrition and the patients' life quality were determined additionally on day 1 and 19. The tumor marker CA 19-9 was measured only on day 1. RESULTS: A latent selenium deficiency was observed while gsh-px activity or concentration of TBARS were normal. The selenium status corresponds to the concentration of the tumor marker CA 19-9. The selenium status improves through supplementation, accompanied by a further increase of GSH-Px activity. During supplementation the patients' life quality improves; subjective physical complaints decrease. CONCLUSION: Further research will be necessary on both the dependency of the selenium status on the tumor marker concentration and on the development of the cancer. Optimum GSH-Px activity and individually different responses also need additional investigation. The influence of selenium on the patients' life quality should be investigated in the context of immunomodulation.

The potential role of unemployment benefits in shaping the mental health impact of unemployment.

This study looks at the association between formal systems of support (unemployment compensation or welfare) and mental health outcomes during periods of unemployment. It assesses whether unemployed persons not receiving unemployment benefits are at greater risk of reporting depression and suffering ill-health than those receiving some kind of unemployment compensation, independent of total household income. The authors performed a secondary analysis of data collected in the National Survey of Families and Households, 1987-1988. Outcome measures included an index of depression and perception of health status. Multiple regression analyses were used. The unemployed receiving unemployment compensation or benefits from other entitlement programs did not report significantly higher depression relative to the employed. Rather, the study found a significantly higher index of depression among unemployed persons receiving welfare benefits or no benefits, even after controlling for total household income and previous employment/unemployment history. Thus unemployment compensation may play an important role in ameliorating the impact of unemployment on depression. By contrast, means-tested benefits may not be sufficient to reduce the risk for reporting depression and suffering ill-health in comparison with the full-time employed. The implications of the findings are discussed in terms of social policy development.

Birth-cohort changes in the rates of mania.

Secular changes in the rates of mania have been reported in the relatives of affectively ill patients, and the present study is an independent replication of these findings in a large probability sample of a community. Data from the five U.S. sites of the National Institute of Mental Health's Epidemiologic Catchment Area study (ECA), a community survey of adults, are presented. A total of 17,827 respondents were divided into eight birth cohorts, each spanning a 10-year interval. Actuarial life-table analyses showed a greater cumulative risk of mania for white men and women from the three most recently born cohorts (i.e., those born after 1935). The Wilcoxon test for homogeneity indicated an overall significant difference by birth cohort. These findings in a community sample are consistent with those previously reported in relatives of affectively ill patients. The results support the hypothesis that birth cohort changes have occurred in the risk of mania and that the risk was greatest in the post-1935 cohorts.