Using PharmGKB to train text mining approaches for identifying potential gene targets for pharmacogenomic studies.

The main objective of this study was to investigate the feasibility of using PharmGKB, a pharmacogenomic database, as a source of training data in combination with text of MEDLINE abstracts for a text mining approach to identification of potential gene targets for pathway-driven pharmacogenomics research. We used the manually curated relations between drugs and genes in PharmGKB database to train a support vector machine predictive model and applied this model prospectively to MEDLINE abstracts. The gene targets suggested by this approach were subsequently manually reviewed. Our quantitative analysis showed that a support vector machine classifiers trained on MEDLINE abstracts with single words (unigrams) used as features and PharmGKB relations used for supervision, achieve an overall sensitivity of 85% and specificity of 69%. The subsequent qualitative analysis showed that gene targets "suggested" by the automatic classifier were not anticipated by expert reviewers but were subsequently found to be relevant to the three drugs that were investigated: carbamazepine, lamivudine and zidovudine. Our results show that this approach is not only feasible but may also find new gene targets not identifiable by other methods thus making it a valuable tool for pathway-driven pharmacogenomics research.

Impact of a prototype visualization tool for new information in EHR clinical documents.

BACKGROUND: EHR clinical document synthesis by clinicians may be time-consuming and error-prone due to the complex organization of narratives, excessive redundancy within documents, and, at times, inadvertent proliferation of data inconsistencies. Development of EHR systems that are easily adaptable to the user's work processes requires research into visualization techniques that can optimize information synthesis at the point of care. OBJECTIVE: To evaluate the effect of a prototype visualization tool for clinically relevant new information on clinicians' synthesis of EHR clinical documents and to understand how the tool may support future designs of clinical document user interfaces. METHODS: A mixed methods approach to analyze the impact of the visualization tool was used with a sample of eight medical interns as they synthesized EHR clinical documents to accomplish a set of four pre-formed clinical scenarios using a think-aloud protocol. RESULTS: Differences in the missing (unretrieved) patient information (2.3±1.2 [with the visualization tool] vs. 6.8±1.2 [without the visualization tool], p = 0.08) and accurate inferences (1.3±0.3 vs 2.3±0.3, p = 0.09) were not statistically significant but suggest some improvement with the new information visualization tool. Despite the non-significant difference in total times to task completion (43±4 mins vs 36±4 mins, p = 0.35) we observed shorter times for two scenarios with the visualization tool, suggesting that the time-saving benefits may be more evident with certain clinical processes. Other observed effects of the tool include more intuitive navigation between patient details and increased efforts towards methodical synthesis of clinical documents. CONCLUSION: Our study provides some evidence that new information visualization in clinical notes may positively influence synthesis of patient information from EHR clinical documents. Our findings provide groundwork towards a more effective display of EHR clinical documents using advanced visualization applications.

Obesity and bariatric surgery: a systematic review of associations with defecatory dysfunction.

BACKGROUND: Obesity rates are rapidly growing in the developed world. While upper gastrointestinal disturbances and urinary incontinence are independently associated with obesity, the relationship between obesity and defecatory dysfunction is less well defined. OBJECTIVES: To summarize the literature on faecal incontinence, diarrhoea and constipation in obese patients and its effects of bariatric surgery. SEARCH STRATEGY: A Medline search was carried out on articles published from January 1966 to March 2010. SELECTION CRITERIA: Original articles on adult obese or morbidly obese patients were identified, including results following bariatric surgery that reported faecal incontinence, diarrhoea or constipation. Other forms of pelvic floor dysfunction were excluded. Main outcome measures included faecal incontinence, diarrhoea and constipation rates and their severity in obese patients and following bariatric surgery. RESULTS: Twenty studies reported defecatory outcomes in obese patients (n = 14) and after bariatric surgery (n = 6). While constipation rates were similar, the rates of faecal incontinence and diarrhoea were higher in obese patients compared with non-obese patients. The exact rates of these conditions, and the correlations between body mass index (BMI) and faecal incontinence, diarrhoea and constipation, were not clear. Faecal incontinence improved after Roux-en-Y gastric bypass in studies with preoperative data. The effects of bariatric surgery on diarrhoea were unclear. CONCLUSION: Few studies have assessed the correlations between obesity and defecatory function and the effect of bariatric surgery. Studies were often not well controlled and used non-uniform instruments to assess bowel function. Obesity appears to be correlated with higher rates of faecal incontinence and diarrhoea. The effects of bariatric surgery on these conditions are not well defined. Well-controlled studies correlating outcome with physiological pelvic floor function are needed.

Analysis of free text with omaha system targets in community-based care to inform practice and terminology development.

The Omaha system is one of the most widely used interface terminologies for documentation of community-based care. It is influential in disseminating evidence-based practice and generating data for health care quality research. Thus, it is imperative to ensure that the Omaha system reflects current health care knowledge and practice. The purpose of this study was to evaluate free text associated with Omaha system terms to inform issues with electronic health record system use and future Omaha system standard development. Two years of client records from two diverse sites (a skilled homecare, hospice, and palliative care program and a maternal child health home visiting program) were analyzed for the use of free text as a component of the intervention when structured targets for interventions were not identified. Intervention text entries very commonly contained duplicate "carry forward entries", multiple concepts, mismatched problem focus, or failure to identify an existing appropriate target. Our findings support the need to better address education gaps for clinicians. We identified additional suggested targets for Omaha system problems, and propose new targets for consideration in future Omaha system revisions.

Do preoperative factors predict subsequent diagnosis of Crohn's disease after ileal pouch-anal anastomosis for ulcerative or indeterminate colitis?

AIM: The aim of this study was to determine preoperative clinical factors associated with subsequent diagnosis revision to Crohn's disease (CD) following total proctocolectomy with ileal pouch-anal anastomosis (IPAA) for ulcerative colitis (UC) or indeterminate colitis (IC) patients. METHOD: Presumed UC and IC patients undergoing IPAA from a large single-institution prospective database with change of diagnosis to CD were identified and compared with patients without diagnosis change. RESULTS: A total of 2814 patients (47% male, median age 37 years) with presumed UC (85%) or IC (15%) underwent primary IPAA. At a median follow up of 9.6 years, 184 (7%) had the diagnosis revised to CD from histopathological examination of the colectomy specimen immediately in 97 (53%) or at a median interval of 36 months in 87 (47%). CD and UC/IC patients had had a similar operative technique, length of stay and 30-day morbidity. The postoperative CD diagnosis was associated with a preoperative diagnosis of IC (P < 0.0001) and perianal fistula (P = 0.002). Patients with a delayed diagnosis of CD were associated with a 3-stage procedure (P < 0.0001, OR = 2.8) (95% CI = 1.8-4.4), colonic stricture (P = 0.04, OR = 2.9 [95% CI = 1.1-7.4]), perianal fistula (P = 0.02, OR = 2.9 [95% CI = 1.2-7.2]), oral ulceration (P = 0.009, OR = 3.8 [95% CI = 1.2-9.6]) and younger age (P < 0.0001, OR = 0.048 [95% CI = 0.011-0.19]). CONCLUSION: A few patients having IPAA for presumed UC/IC were subsequently diagnosed to have CD which was associated with perianal fistula and the diagnosis of postoperative preoperative IC. The delayed diagnosis of CD was associated with a three-stage procedure, colorectal stricture, anal fissure, mouth ulceration and younger age.

Children's law: toward a new realism.

The realist approach that has dominated American jurisprudence has long had especially great acceptance in regard to children's issues. Ironically, however, decision making on such topics has seemed to be particularly unlikely to be informed by careful assessments of social reality. Symbolism has prevailed over pragmatism. Psycholegal research on children's issues has also often been misdirected. Application of the Convention on the Rights of the Child may point the way to more psychologically minded children's law.

Postoperative bile duct strictures: management and outcome in the 1990s.

OBJECTIVE: To describe the management and outcome after surgical reconstruction of 156 patients with postoperative bile duct strictures managed in the 1990s. SUMMARY BACKGROUND DATA: The management of postoperative bile duct strictures and major bile duct injuries remains a challenge for even the most skilled biliary tract surgeon. The 1990s saw a dramatic increase in the incidence of bile duct strictures and injuries from the introduction and widespread use of laparoscopic cholecystectomy. Although the management of these injuries and short-term outcome have been reported, long-term follow-up is limited. METHODS: Data were collected prospectively on 156 patients treated at the Johns Hopkins Hospital with major bile duct injuries or postoperative bile duct strictures between January 1990 and December 1999. With the exception of bile duct injuries discovered and repaired during surgery, all patients underwent preoperative percutaneous transhepatic cholangiography and placement of transhepatic biliary catheters before surgical repair. Follow-up was conducted by medical record review or telephone interview during January 2000. RESULTS: Of the 156 patients undergoing surgical reconstruction, 142 had completed treatment with a mean follow-up of 57.5 months. Two patients died of reasons unrelated to biliary tract disease before the completion of treatment. Twelve patients (7.9%) had not completed treatment and still had biliary stents in place at the time of this report. Of patients who had completed treatment, 90. 8% were considered to have a successful outcome without the need for follow-up invasive, diagnos tic, or therapeutic interventional procedures. Patients with reconstruction after injury or stricture after laparoscopic cholecystectomy had a better overall outcome than patients whose postoperative stricture developed after other types of surgery. Presenting symptoms, number of stents, interval to referral, prior repair, and length of postoperative stenting were not significant predictors of outcome. Overall, a successful outcome, without the need for biliary stents, was obtained in 98% of patients, including those requiring a secondary procedure for recurrent stricture. CONCLUSIONS: Major bile duct injuries and postoperative bile duct strictures remain a considerable surgical challenge. Management with preoperative cholangiography to delineate the anatomy and placement of percutaneous biliary catheters, followed by surgical reconstruction with a Roux-en-Y hepaticojejunostomy, is associated with a successful outcome in up to 98% of patients.

Patterns and correlates of gun ownership among nonmetropolitan and rural middle school students.

Examined prevalence of gun ownership and the links among gun ownership, reasons for gun ownership, and antisocial behavior in a sample of nonmetropolitan and rural middle school students. Participants completed the Questionnaire for Students (Olweus, 1995) and included 6,263 students from 36 elementary and middle schools, of whom most were African American (range = 46%-95% per school). Reasons for gun ownership were strongly associated with rates of antisocial behavior. Youths who owned guns for sporting reasons reported rates of antisocial behavior that were only slightly higher than those reported by youths who did not own guns. Youths who owned guns to gain respect or to frighten others reported extremely high rates of antisocial behavior. These high-risk adolescent gun owners were likely to come from families of high-risk gun owners, associate with friends who were high-risk gun owners, and engage in high rates of bullying behavior. Findings suggest that effective violence prevention programs must target high-risk youths, address risk factors that go beyond individual settings, and address a comprehensive array of risk factors.

CpG oligodeoxynucleotides and interleukin-12 improve the efficacy of Mycobacterium bovis BCG vaccination in mice challenged with M. tuberculosis.

Mycobacterium bovis bacillus Calmette-Guérin (BCG) is the only vaccine approved for prevention of tuberculosis. It has been postulated that serial passage of BCG over the years may have resulted in attenuation of its effectiveness. Because interleukin-12 (IL-12) and oligodeoxynucleotides (ODN) containing cytidine phosphate guanosine (CpG) motifs have been shown to enhance Th1 responses in vivo, they were chosen as adjuvants to increase the effectiveness of BCG vaccination. In this report, mice were vaccinated with BCG with or without IL-12 or CpG ODN and then challenged 6 weeks later via the aerosol route with the Erdman strain of M. tuberculosis. Mice vaccinated with BCG alone showed a 1- to 2-log reduction in bacterial load compared with control mice that did not receive any vaccination prior to M. tuberculosis challenge. Moreover, the bacterial loads of mice vaccinated with BCG plus IL-12 or CpG ODN were a further two- to fivefold lower than those of mice vaccinated with BCG alone. As an immune correlate, the antigen-specific production IFN-gamma and mRNA expression in spleen cells prior to challenge were evaluated. Mice vaccinated with BCG plus IL-12 or CpG ODN showed enhanced production of IFN-gamma compared with mice vaccinated with BCG alone. Finally, granulomas in BCG-vaccinated mice were smaller and more lymphocyte rich than those in unvaccinated mice; however, the addition of IL-12 or CpG ODN to BCG vaccination did not alter granuloma formation or result in added pulmonary damage. These observations support a role for immune adjuvants given with BCG vaccination to enhance its biologic efficacy.

Multisystemic therapy with violent and chronic juvenile offenders and their families: the role of treatment fidelity in successful dissemination.

The effects of multisystemic therapy (MST) in treating violent and chronic juvenile offenders and their families in the absence of ongoing treatment fidelity checks were examined. Across 2 public sector mental health sites, 155 youths and their families were randomly assigned to MST versus usual juvenile justice services. Although MST improved adolescent symptomology at posttreatment and decreased incarceration by 47% at a 1.7-year follow-up, findings for decreased criminal activity were not as favorable as observed on other recent trials of MST. Analyses of parent, adolescent, and therapist reports of MST treatment adherence, however, indicated that outcomes were substantially better in cases where treatment adherence ratings were high. These results highlight the importance of maintaining treatment fidelity when disseminating complex family-based services to community settings.

Double-blind study of pulsing magnetic field effects on multiple sclerosis.

We performed a double-blind study to measure the clinical and subclinical effects of an alternative medicine magnetic device on disease activity in multiple sclerosis (MS). The MS patients were exposed to a magnetic pulsing device (Enermed) where the frequency of the magnetic pulse was in the 4-13 Hz range (50-100 milliGauss). A total of 30 MS patients wore the device on preselected sites between 10 and 24 hours a day for 2 months. Half of the patients (15) randomly received an Enermed device that was magnetically inactive and the other half received an active device. Each MS patient received a set of tests to evaluate MS disease status before and after wearing the Enermed device. The tests included (1) a clinical rating (Kurtzke, EDSS), (2) patient-reported performance scales, and (3) quantitative electroencephalography (QEEG) during a language task. Although there was no significant change between pretreatment and posttreatment in the EDSS scale, there was a significant improvement in the performance scale (PS) combined rating for bladder control, cognitive function, fatigue level, mobility, spasticity, and vision (active group -3.83 +/- 1.08, p < 0.005; placebo group -0.17 +/- 1.07, change in PS scale). There was also a significant change between pretreatment and posttreatment in alpha EEG magnitude during the language task recorded at various electrode sites on the left side. In this double-blind, placebo-controlled study, we have demonstrated a statistically significant effect of the Enermed magnetic pulsing device on patient performance scales and on alpha EEG magnitude during a language task.

The child's right to a family environment. Why children's rights and family values are compatible.

Critics of the Convention on the Rights of the Child (U.N. General Assembly, 1989) have lobbied against its ratification on the grounds that its impact in the United States would be antifamily. Careful reading of the Convention shows, however, that it not only is supportive of strong families but offers a creative and conceptually coherent foundation for government action to promote and protect family life.

Doing justice and doing good: conflicts for mental health professionals.

The primary role of mental health professionals in cases of child abuse should be to treat the victims and the offenders. Currently, however, mental health professionals are often involved in the investigation and adjudication of child sexual abuse claims. This article discusses the conceptual and practical conflicts this involvement creates with the mental health professional's therapeutic role. The author concludes that mental health professionals should not be involved in investigating child sexual abuse cases. Furthermore, he contends that mental health testimony about the victim should never be allowed during the adjudication stage and that mental health testimony about the defendant should be allowed only if the defendant puts his character into question. The scientific knowledge base for such testimony is very limited, and the testimony is likely to be more misleading and prejudicial than helpful. Mental health professionals, however, could appropriately help children and adults prepare for legal proceedings and facilitate mediation.

Children in war and its aftermath: mental health issues in the development of international law.

Children now experience war as they never have in the past. This article presents clinical impressions of children from war zones and suggests interventions that might ameliorate the horrors of war for some of these children. It also describes the evolving framework in international law (i.e., the United Nations) that provides a context for implementing some of these interventions and for insulating children from some of the devastating effects of war.

Assessing violent offending in serious juvenile offenders.

The convergent validity of the two most frequently used methods for assessing violent offending in juveniles (i.e., self-reports and arrests) was evaluated. Participants were 87 serious juvenile offenders and their maternal figures, primarily from disadvantaged families. Validation measures tapped established behavioral, family, and peer correlates of delinquency. Results failed to support the ability of either arrests for violent crimes or self-reported violent offenses to index violent criminal behavior accurately. Several methodological features of the study support our hypothesis that the findings were not spurious. Procedural and conceptual implications of the findings are discussed.

Family preservation using multisystemic therapy: an effective alternative to incarcerating serious juvenile offenders.

Multisystemic therapy (MST) delivered through a community mental health center was compared with usual services delivered by a Department of Youth Services in the treatment of 84 serious juvenile offenders and their multiproblem families. Offenders were assigned randomly to treatment conditions. Pretreatment and posttreatment assessment batteries evaluating family relations, peer relations, symptomatology, social competence, and self-reported delinquency were completed by the youth and a parent, and archival records were searched at 59 weeks postreferral to obtain data on rearrest and incarceration. In comparison with youths who received usual services, youths who received MST had fewer arrests and self-reported offenses and spent an average of 10 fewer weeks incarcerated. In addition, families in the MST condition reported increased family cohesion and decreased youth aggression in peer relations. The relative effectiveness of MST was neither moderated by demographic characteristics nor mediated by psychosocial variables.

Avoiding heterosexist bias in psychological research.

The authors describe various ways that heterosexist bias can occur in scientific research and suggest ways that social and behavioral scientists can avoid it. Heterosexist bias is defined as conceptualizing human experience in strictly heterosexual terms and consequently ignoring, invalidating, or derogating homosexual behaviors and sexual orientation, and lesbian, gay male, and bisexual relationships and lifestyles. The deleterious scientific, social, and ethical consequences of such biases are discussed. Questions are provided for researchers to use in evaluating how heterosexist bias might affect their own selection of research questions, sampling, operationalization of variables, data collection, protection of participants, and dissemination of results. Suggestions also are offered for reducing heterosexist bias in academic journals, in textbooks, and in colleges and universities.

Preserving the dignity of children around the world: the U.N. Convention on the Rights of the Child.

The United Nations Convention on the Rights of the Child provides a guidepost to the development of child protection policy. Both comprehensive and conceptually coherent, the Convention provides a statement of international consensus that children are indeed persons, legally and morally, and that the state should ensure that they are treated with dignity. At least in spirit, the Convention demands substantial reform of most existing child protection systems.