Pearls and Pitfalls of Team Science.

Formidable health problems are often best addressed by teams of scientists with varied expertise. This diversity among team members and complexities in managing teams can lead to challenges in designing, funding, conducting, and reporting research. Team science difficulties can be addressed by sophisticated planning, frequent reassessment and realignment of team strategies with goals, and consistent transparent communication. This article addresses specific strategies to build and sustain research teams, manage team meetings, strategically develop publications and grants, thrive in the midst of disciplinary and individual team member differences, embrace new ideas and change to maintain creativity, and build future team scientists and projects. The potential value in team science justifies the effort required to build and maintain efficient and effective research teams.

The learning experiences of immigrants who are graduates of an entry-level baccalaureate nursing program: A hermeneutic phenomenological study.

International migration of individuals or families seeking to improve economic conditions or escape political oppression increases each year. With migrant movement, there is a need for appropriate health care to meet their health beliefs and cultural health traditions. Nurses comprise a large portion of the healthcare workforce and yet, the number of immigrant nurses educated in their adopted country remains low. The aim of this study was to understand the learning experiences of immigrant registered nurses who graduated from an entry-level baccalaureate nursing program in the United States. A hermeneutic phenomenological approach with a Gadamerian focus was utilized. Purposive sampling identified five immigrant graduates who were individually interviewed using several open-ended questions in a non-structured format. Analysis identified an overarching theme, "being on the outside." Five subthemes emerged: harsh realities, disruptions, nurturance, resilience, and propagation. Recommendations from the interviews include: recognition and appreciation of each student, the nurse educator coming to know oneself first, followed by dialoguing with each student to perpetuate deeper understanding. Rather than accommodating the ethnically diverse immigrant nursing student through targeted interventions, the nurse educator should maintain an all-inclusive learning environment.

Launching Successful Beginnings for Early Career Faculty Researchers.

Junior faculty follow a research path replete with challenges as they strive to create knowledge in their area of interest while balancing new responsibilities. Unlike graduate school, where students focus inward on personal development, junior faculty must add responsibilities in ways that hold them accountable as members of a university. This special article deals with three themes of interest to new junior faulty launching research programs: personal development, collaboration and team development within university settings, and funding advice. Strategies in these areas provide guidance on navigating early careers and finding success in the academic setting.

Effects of Amitriptyline and Escitalopram on Sleep and Mood in Patients With Functional Dyspepsia.

BACKGROUND & AIMS: Tricyclic antidepressants are effective in reducing symptoms of functional dyspepsia (FD). We performed a post hoc analysis of data from a previous randomized clinical trial to determine whether the benefits of an antidepressant on gastrointestinal symptoms in patients with FD were mediated by improving sleep or reducing anxiety. We explored the relationships between psychological measures, quality of sleep, and relief of symptoms. METHODS: We analyzed data from a multicenter, double-blind trial that evaluated the efficacy of antidepressants on symptoms of FD, from October 2006 through October 2012. Patients (n = 292) were randomly assigned to groups given 50 mg amitriptyline, 10 mg escitalopram, or placebo for 12 weeks. During the study, participants completed the following validated psychological questionnaires: Symptom Check List 90, Symptom Somatic Checklist, Hospital Anxiety Depression Scale, Profile of Mood States, State Trait Anxiety Inventory, and Pittsburgh Sleep Quality Index at baseline and 12 weeks following treatment. RESULTS: Baseline scores for the psychological and sleep measures were similar among groups; after 12 weeks there were no significant differences in scores among groups. Baseline mean global Pittsburgh Sleep Quality Index scores indicated poor sleep quality in all groups at baseline and after 12 weeks. Overall, antidepressants affected sleep duration scores: patients given amitriptyline had lower (better) scores than patients given placebo or escitalopram (P = .019). In all groups, responders had decreased anxiety and improvements in some sleep components. CONCLUSIONS: In a post hoc analysis of data from a clinical trial that evaluated the effects of antidepressants in patients with FD, amitriptyline was found to reduce symptoms of FD, but its mechanism is unlikely to involve reductions in psychological distress. The drug may modestly improve sleep. Clinicaltrials.gov no: NCT00248651.

Identification and validation of functional gastrointestinal disorder subtypes using latent class analysis: a population-based study.

OBJECTIVE: Attempts to categorize distinct functional gastrointestinal disorders based on reported symptoms continue but symptoms frequently overlap. The study objective was to use latent class analysis (LCA) which accommodates both continuous and discrete manifest variables to determine mutually exclusive subgroup assignments of a population-based sample using gastrointestinal symptom and patient data. MATERIALS AND METHODS: A validated bowel disease questionnaire and somatic symptom questionnaire were mailed to an age and gender stratified randomly selected community sample. Responses to the symptom questions were dichotomized as frequent vs. infrequent based on Rome IV criteria. A LCA model was developed using a calibration subset and the results applied to the validation subset. RESULTS: There were 3831 total respondents (48%) with 3425 having complete data. The LCA algorithm was run for each of 10 (random) splits of the dataset and 2-6 latent classes were specified. Using the values of Akaike's Information Criterion coefficient c to determine fit of the data, 4 latent classes yielded better values resulting in four subgroups: 'asymptomatic,' 'upper' abdominal symptoms, 'lower' abdominal symptoms, and 'mixed' (upper and lower abdomen). CONCLUSIONS: Latent class analysis identified 4 groups based on symptoms. This approach resulted in differentiation by anatomical region rather than the Rome IV classification of symptoms.

Polymorphisms of 5-HTT LPR and GNß3 825C>T and Response to Antidepressant Treatment in Functional Dyspepsia: A Study from The Functional Dyspepsia Treatment Trial.

OBJECTIVES: The Functional Dyspepsia Treatment Trial reported that amitriptyline (AMI) was associated with adequate relief of functional dyspepsia (FD) symptoms, but the pharmacogenetics of antidepressant response in FD are not known. GNß3 825C>T CC genotype has been previously linked to FD and TT genotype to antidepressant response in depression. The ss genotype of the 5-HTT LPR variant of the serotonin transporter gene (SLC6A4) has been linked to selective serotonin reuptake inhibitor (SSRI) response. We aimed to examine whether GNß3 825C>T and 5-HTT LPR polymorphisms result in differential treatment effects in FD patients receiving antidepressant therapy. METHODS: Participants were randomized to receive placebo, 50 mg AMI, or 10 mg escitalopram (ESC). The primary end point was adequate relief for ≥5 weeks of the last 10 weeks. Genotyping of GNß3 825C>T and 5-HTT LPR was performed utilizing PCR-based methods. RESULTS: GNß3 825C>T and 5-HTT LPR genotype data were available for 256 (88%) and 246 (84%) patients, respectively. Both polymorphisms were in Hardy-Weinberg equilibrium. In tests for differential treatment, neither 5-HTT LPR nor GNß3 825C>T genotype influenced response to therapy (P=0.89 and P=0.54, respectively). Although there was a tendency for a more favorable response to ESC in the SS/LS genotype compared to the LL genotype groups (40% vs. 31% reporting adequate relief of FD symptoms) among those in the ESC treatment arm, this was not significant (P=0.43). CONCLUSIONS: GNß3 825C>T and 5-HTT LPR genetic variants do not alter treatment response to tricyclic and SSRI antidepressants in FD.

A case-control comparison of direct healthcare-provider medical costs of chronic idiopathic constipation and irritable bowel syndrome with constipation in a community-based cohort.

OBJECTIVE: Patients with constipation account for 3.1 million US physician visits a year, but care costs for patients with irritable bowel syndrome with constipation (IBS-C) or chronic idiopathic constipation (CIC) compared to the general public have received little study. The study aim was to describe healthcare utilization and compare medical costs for patients with IBS-C or CIC vs matched controls from a community-based sample. METHODS: A nested case-control sample (IBS-C and CIC cases) and matched controls (1:2) for each case group were selected from Olmsted County, MN, individuals responding to a community-based survey of gastrointestinal symptoms (2008) who received healthcare from a participating Rochester Epidemiology Project (REP) provider. Using REP healthcare utilization data, unadjusted and adjusted standardized costs were compared for the 2- and 10-year periods prior to the survey for 115 IBS-C patients and 230 controls and 365 CIC patients and 730 controls. Two time periods were chosen as these conditions are episodic, but long-term. RESULTS: Outpatient costs for IBS-C ($6,800) and CIC ($6,284) patients over a 2-year period prior to the survey were significantly higher than controls ($4,242 and $5,254, respectively) after adjusting for co-morbidities, age, and sex. IBS-C outpatient costs ($25,448) and emergency room costs ($6,892) were significantly higher than controls ($21,024 and $3,962, respectively) for the 10-year period prior. Unadjusted data analyses of cases compared to controls demonstrated significantly higher imaging costs for IBS-C cases and procedure costs for CIC cases over the 10-year period. LIMITATIONS: Data were collected from a random community sample primarily receiving care from a limited number of providers in that area. CONCLUSIONS: Patients with IBS-C and CIC had significantly higher outpatient costs for the 2-year period compared with controls. IBS-C patients also had higher ER costs than the general population.

Effect of Amitriptyline and Escitalopram on Functional Dyspepsia: A Multicenter, Randomized Controlled Study.

BACKGROUND & AIMS: Antidepressants are frequently prescribed to treat functional dyspepsia (FD), a common disorder characterized by upper abdominal symptoms, including discomfort or postprandial fullness. However, there is little evidence of the efficacy of these drugs in patients with FD. We performed a randomized, double-blind, placebo-controlled trial to evaluate the effects of antidepressant therapy on symptoms, gastric emptying (GE), and meal-induced satiety in patients with FD. METHODS: We performed a study at 8 North American sites of patients who met the Rome II criteria for FD and did not have depression or use antidepressants. Patients (n = 292; 44 ± 15 years old, 75% were female, 70% with dysmotility-like FD, and 30% with ulcer-like FD) were randomly assigned to groups given placebo, 50 mg amitriptyline, or 10 mg escitalopram for 10 weeks. The primary end point was adequate relief of FD symptoms for ≥5 weeks of the last 10 weeks (of 12). Secondary end points included GE time, maximum tolerated volume in Nutrient Drink Test, and FD-related quality of life. RESULTS: An adequate relief response was reported by 39 subjects given placebo (40%), 51 given amitriptyline (53%), and 37 given escitalopram (38%) (P = .05, after treatment, adjusted for baseline balancing factors including all subjects). Subjects with ulcer-like FD given amitriptyline were >3-fold more likely to report adequate relief than those given placebo (odds ratio = 3.1; 95% confidence interval: 1.1-9.0). Neither amitriptyline nor escitalopram appeared to affect GE or meal-induced satiety after the 10-week period in any group. Subjects with delayed GE were less likely to report adequate relief than subjects with normal GE (odds ratio = 0.4; 95% confidence interval: 0.2-0.8). Both antidepressants improved overall quality of life. CONCLUSIONS: Amitriptyline, but not escitalopram, appears to benefit some patients with FD, particularly those with ulcer-like (painful) FD. Patients with delayed GE do not respond to these drugs. ClinicalTrials.gov ID: NCT00248651.

Dyspepsia in the community: value of a community-based mailed survey to identify potential participants for a randomized clinical trial.

OBJECTIVE: To assess the usefulness of a community-based mailed survey to identify participants with functional dyspepsia (FD) for a clinical trial. MATERIAL AND METHODS: In 2008, a valid self-report questionnaire of gastrointestinal symptoms required for diagnosis of FD was mailed to randomly selected cohorts of Olmsted County, Minnesota, residents. From survey responses (54%), FD cases and controls were identified. Phone calls were completed in 2010 and 2011 to 54% of respondents offering participation to those meeting criteria. RESULTS: Of 937 people identified from the survey, 189 cases and 265 controls were contacted by phone using four questions similar to the written survey resulting in a moderate level of agreement (Kappa 0.43, 95% CI: 0.35- 0.51; p = 0.11). The proportion reporting FD symptoms by survey was 42%, while the proportion by phone was 38%. Comparing classification of cases and controls, 118 (62%) survey cases had dyspepsia symptoms on phone screening while 53 (20%) of the survey controls reported FD symptoms. Of 171 who had symptoms, 60 (35%) declined, 33 (19%) were over study age limit, 24 (14%) had inadequate symptom levels and 36 (21%) had comorbidities. Of survey respondents contacted, six (3%) people were enrolled with two screen fails resulting in four (1%) randomized. CONCLUSION: Agreement between survey and phone questions was modest. Classifications between case and control changed. People eligible and willing to participate were a fraction of people reporting symptoms. People participating in clinical trials do not broadly represent those in the population.

Evaluating an educational intervention on lateral violence.

BACKGROUND: Lateral violence involves disruptive behaviors that lead to toxic work environments. The purpose of this project was to determine the effects of an educational intervention to increase awareness and teach cognitive rehearsal to combat lateral violence. METHOD: A one-time pretest-posttest evaluation design was used to evaluate the effects of a 1.5-hour educational intervention. Participants were nurses on two nursing units; 29 respondents participated in the pretest, and 25 respondents participated in the posttest. RESULTS: Positive trends were related to the decreasing frequency of lateral violence behaviors experienced and observed after the intervention. Participants were better able to identify causes of lateral violence in their work units, suggesting the educational intervention was successful in creating a healthier work environment and decreasing the incidence of lateral violence behaviors. CONCLUSION: Further evaluation is needed to determine whether the intervention would be effective over time. This project was limited by design and sample size.

Challenges and lessons learned in conducting comparative-effectiveness trials.

The current health-care environment is demanding evidence-based medicine that relies on clinical trials as the basis for decisions. Clinician investigators are more often finding that they are personally responsible for coordinating large, multisite trials. We present strategies for successful implementation and management of multisite clinical trials and knowledge gained through an international, multisite randomized clinical trial. Topics include team composition, regulatory requirements, study organization and governance, communication strategies, recruitment and retention efforts, budget, technology transfer, and publication.

Functional Dyspepsia Treatment Trial (FDTT): a double-blind, randomized, placebo-controlled trial of antidepressants in functional dyspepsia, evaluating symptoms, psychopathology, pathophysiology and pharmacogenetics.

BACKGROUND: Functional dyspepsia (FD) is a common problem affecting up to 10-25% of individuals. FD accounts for significant health care costs and affects quality of life but has no definitive treatment. OBJECTIVES: The Functional Dyspepsia Treatment Trial (FDTT) aims to test whether treatment with an antidepressant (amitriptyline or escitalopram) leads to improvement of symptoms in patients with moderate to severe FD. DESIGN: The FDTT is an international multicenter, parallel group, randomized, double-blind, placebo-controlled trial to evaluate whether 12 weeks of treatment with escitalopram or amitriptyline improves FD symptoms compared to treatment with placebo. Secondly, it is hypothesized that acceleration of solid gastric emptying, reduction of postprandial satiation, and enhanced gastric volume change with a meal will be significant positive predictors of short- and long-term outcomes for those on antidepressants vs. placebo. The third aim is to examine whether polymorphisms of GNß3 and serotonin reuptake transporter influence treatment outcomes in FD patients receiving a tricyclic antidepressant, selective serotonin reuptake inhibitor therapy, or placebo. METHODS: The FDTT enrollment began in 2006 and is scheduled to randomize 400 patients by the end of 2012 to receive an antidepressant or placebo for 12 weeks, with a 6-month post-treatment follow-up. The study incorporates multiple validated questionnaires, physiological testing, and specific genetic evaluations. The protocol was approved by participating centers' Institutional Review Boards and an independent Data Safety Monitoring Board was established for monitoring to ensure patient safety and a single interim review of the data in December 2010 (ClinicalTrials.gov number NCT00248651).

Irritable bowel syndrome and chronic pelvic pain: a population-based study.

BACKGROUND: Women with irritable bowel syndrome (IBS) frequently report chronic pelvic pain, however, it is still unanswered whether these are truly separate entities. IBS negatively impacts on quality of life, but the impact of IBS on sexual function is not clear. GOALS: We aimed to (1) describe the impact of IBS on sexual function, and (2) evaluate the association between pelvic pain and IBS, and in particular identify if there are unique characteristics of the overlap group. STUDY: The Talley Bowel Disease Questionnaire was mailed to an age- and gender-stratified random sample of 1031 Olmsted County, Minnesota residents aged 30 to 64 years. Manning (at least 2 of 6 positive) and Rome criteria (Rome I and modified Rome III) were used to identify IBS. Pelvic pain was assessed by a single item. Somatization was assessed by the valid somatic symptom checklist. RESULTS: Overall 648 (69%) of 935 eligible participants responded (mean age 52 years, 52% female). Self-reported sexual dysfunction was rare (0.9%; 95% CI 0.3-2.0%). Among women, 20% (95% CI 16-24%) reported pain in the pelvic region; 40% of those with pelvic pain met IBS by Manning, or Rome criteria. IBS and pelvic pain occurred together more commonly than expected by chance (P<0.01). The overall somatization score (and specifically the depression and dizziness item scores) predicted IBS-pelvic pain overlap versus either IBS alone or pelvic pain alone. CONCLUSION: In a subset with pelvic pain, there is likely to be a common underlying psychologic process (somatization) that explains the link to IBS.