Integrating Serum Biomarkers into Prediction Models for Biochemical Recurrence Following Radical Prostatectomy.

This study undertook to predict biochemical recurrence (BCR) in prostate cancer patients after radical prostatectomy using serum biomarkers and clinical features. Three radical prostatectomy cohorts were used to build and validate a model of clinical variables and serum biomarkers to predict BCR. The Cox proportional hazard model with stepwise selection technique was used to develop the model. Model evaluation was quantified by the AUC, calibration, and decision curve analysis. Cross-validation techniques were used to prevent overfitting in the Irish training cohort, and the Austrian and Norwegian independent cohorts were used as validation cohorts. The integration of serum biomarkers with the clinical variables (AUC = 0.695) improved significantly the predictive ability of BCR compared to the clinical variables (AUC = 0.604) or biomarkers alone (AUC = 0.573). This model was well calibrated and demonstrated a significant improvement in the predictive ability in the Austrian and Norwegian validation cohorts (AUC of 0.724 and 0.606), compared to the clinical model (AUC of 0.665 and 0.511). This study shows that the pre-operative biomarker PEDF can improve the accuracy of the clinical factors to predict BCR. This model can be employed prior to treatment and could improve clinical decision making, impacting on patients' outcomes and quality of life.

Harmonising the human biobanking consent process: an Irish experience.

Biobanks are repositories of human biological samples and data. They are an important component of clinical research in many disease areas and often represent the first step toward innovative treatments. For biobanks to operate, researchers need human participants to give their samples and associated health data. In Ireland, research participants must provide their freely given informed consent for their samples and data to be taken and used for research purposes. Biobank staff are responsible for communicating the relevant information to participants prior to obtaining their consent, and this communication process is supported by documentation in the form of Participant Information Leaflets and Informed Consent Forms (PILs/ICFs). PILs/ICFs should be concise, intelligible, and contain relevant information. While not a substitute for layperson and research staff discussions, PILs and ICFs ensure that a layperson has enough information to make an informed choice to participate or not. However, PILs/ICFs are often lengthy, contain technical language and can be complicated and onerous for a layperson to read. The introduction of the General Data Protection Regulation (GDPR) and the related Irish Health Research Regulation (HRR) presented additional challenges to the Irish biobank community. In May 2019, the National Biobanking Working Group (NBWG) was established in Ireland. It consists of members from diverse research backgrounds located in universities, hospitals and research centres across Ireland and a public/patient partner. The NBWG aimed to develop a suite of resources for health research biobanks via robust and meaningful patient engagement, which are accessible, GDPR/HRR-compliant and could be used nationally, including a PIL/ICF template. This open letter describes the process whereby this national biobank PIL/ICF template was produced. The development of this template included review by the Patient Voice in Cancer Research, led by Professor Amanda McCann at University College Dublin and the Health Research Data Protection Network.

European Randomised Study of Screening for Prostate Cancer (ERSPC) risk calculators significantly outperform the Prostate Cancer Prevention Trial (PCPT) 2.0 in the prediction of prostate cancer: a multi-institutional study.

OBJECTIVE: To analyse the performance of the Prostate Cancer Prevention Trial Risk Calculator (PCPT-RC) and two iterations of the European Randomised Study of Screening for Prostate Cancer (ERSPC) Risk Calculator, one of which incorporates prostate volume (ERSPC-RC) and the other of which incorporates prostate volume and the prostate health index (PHI) in a referral population (ERSPC-PHI). PATIENTS AND METHODS: The risk of prostate cancer (PCa) and significant PCa (Gleason score ≥7) in 2001 patients from six tertiary referral centres was calculated according to the PCPT-RC and ERSPC-RC formulae. The calculators' predictions were analysed using the area under the receiver-operating characteristic curve (AUC), calibration plots, Hosmer-Lemeshow test for goodness of fit and decision-curve analysis. In a subset of 222 patients for whom the PHI score was available, each patient's risk was calculated as per the ERSPC-RC and ERSPC-PHI risk calculators. RESULTS: The ERSPC-RC outperformed the PCPT-RC in the prediction of PCa, with an AUC of 0.71 compared with 0.64, and also outperformed the PCPT-RC in the prediction of significant PCa (P<0.001), with an AUC of 0.74 compared with 0.69. The ERSPC-RC was found to have improved calibration in this cohort and was associated with a greater net benefit on decision-curve analysis for both PCa and significant PCa. The performance of the ERSPC-RC was further improved through the addition of the PHI score in a subset of 222 patients. The AUCs of the ERSPC-PHI were 0.76 and 0.78 for PCa and significant PCa prediction, respectively, in comparison with AUC values of 0.72 in the prediction of both PCa and significant PCa for the ERSPC-RC (P = 0.12 and P = 0.04, respectively). The ERSPC-PHI risk calculator was well calibrated in this cohort and had an increase in net benefit over that of the ERSPC-RC. CONCLUSIONS: The performance of the risk calculators in the present cohort shows that the ERSPC-RC is a superior tool in the prediction of PCa; however the performance of the ERSPC-RC in this population does not yet warrant its use in clinical practice. The incorporation of the PHI score into the ERSPC-PHI risk calculator allowed each patient's risk to be more accurately quantified. Individual patient risk calculation using the ERSPC-PHI risk calculator can be undertaken in order to allow a systematic approach to patient risk stratification and to aid in the diagnosis of PCa.

Improving multivariable prostate cancer risk assessment using the Prostate Health Index.

OBJECTIVES: To analyse the clinical utility of a prediction model incorporating both clinical information and a novel biomarker, p2PSA, in order to inform the decision for prostate biopsy in an Irish cohort of men referred for prostate cancer assessment. PATIENTS AND METHODS: Serum isolated from 250 men from three tertiary referral centres with pre-biopsy blood draws was analysed for total prostate-specific antigen (PSA), free PSA (fPSA) and p2PSA. From this, the Prostate Health Index (PHI) score was calculated (PHI = (p2PSA/fPSA)*√tPSA). The men's clinical information was used to derive their risk according to the Prostate Cancer Prevention Trial (PCPT) risk model. Two clinical prediction models were created via multivariable regression consisting of age, family history, abnormality on digital rectal examination, previous negative biopsy and either PSA or PHI score, respectively. Calibration plots, receiver-operating characteristic (ROC) curves and decision curves were generated to assess the performance of the three models. RESULTS: The PSA model and PHI model were both well calibrated in this cohort, with the PHI model showing the best correlation between predicted probabilities and actual outcome. The areas under the ROC curve for the PHI model, PSA model and PCPT model were 0.77, 0.71 and 0.69, respectively, for the prediction of prostate cancer (PCa) and 0.79, 0.72 and 0.72, respectively, for the prediction of high grade PCa. Decision-curve analysis showed a superior net benefit of the PHI model over both the PSA model and the PCPT risk model in the diagnosis of PCa and high grade PCa over the entire range of risk probabilities. CONCLUSION: A logical and standardized approach to the use of clinical risk factors can allow more accurate risk stratification of men under investigation for PCa. The measurement of p2PSA and the integration of this biomarker into a clinical prediction model can further increase the accuracy of risk stratification, helping to better inform the decision for prostate biopsy in a referral population.

Unusual childhood presentations of abdominal non-Hodgkin's lymphoma.

Non-Hodgkin's lymphoma (NHL) is a relatively common childhood cancer that can present in a myriad of ways. It is essential that NHL is included in the differential diagnosis of children presenting with an abdominal complaint, especially those with unexplained or prolonged symptoms. We describe three acute pediatric presentations of abdominal NHL, two of which presented as acute abdomen (the first mimicking intussusception and the second appendicitis), and the third involving lower limb edema. This case series illustrates the array of presentations of abdominal NHL and the diagnostic challenges that they can provide.

Disseminating perinatal depression screening as a public health initiative: a train-the-trainer approach.

This case report describes the development and implementation of the Train-the-Trainer: Maternal Depression Screening Program (TTT), a novel approach to disseminating perinatal depression screening. We trained screeners according to a standard pyramid scheme of train-the-trainer programs: three experts trained representatives from health care agencies (the TTT trainers), who in turn trained their staff and implemented depression screening at their home agencies. The TTT trainers had little or no prior mental health experience so "enhanced" components were added to ensure thorough instruction. Although TTT was implemented primarily as a services project, we evaluated both the statewide dissemination and the screening rates achieved by TTT programs. Thirty-two social service or health agencies implemented maternal depression screening in 20 counties throughout Iowa; this reached 58.2% of the Iowa population. For the 16 agencies that provided screening data, the average screening rate (number of women screened/number eligible to be screened) for the first 3 months of screening was 73.2%, 80.5% and 79.0%. We compared screening rates of our TTT programs with those of Healthy Start, a program in which screening was established via an intensive consultation model. We found the screening rates in 62.5% of TTT agencies were comparable to those in Healthy Start. Our "enhanced" train-the-trainer method is a promising approach for broadly implementing depression-screening programs in agencies serving pregnant and postpartum women.

Predictors of the longitudinal course of postpartum depression following interpersonal psychotherapy.

OBJECTIVE: We examined the course and predictors of postpartum depression in the 18 months following interpersonal psychotherapy (IPT). METHOD: We enrolled 120 community women with major depression in a 12-week randomized trial of individual IPT during the postpartum period (O'Hara, Stuart, Gorman, & Wenzel, 2000). At 6, 12, and 18 months posttreatment, women participated in clinical interviews to establish the course of depression over the previous 6 months. We used survival analyses to characterize recovery and recurrence in the follow-up and growth curve modeling techniques to identify predictors of change in depression during the follow-up period. Potential predictors included severity, chronicity, and personal history of depression. RESULTS: Of 35 women who recovered with acute treatment, 20 (57%) achieved sustained recovery during follow-up; average time to recurrence was 33.40 weeks (SD = 18.43 weeks). Over 80% of women who did not recover with acute treatment experienced recovery at some point during follow-up; average time to recovery was 28.60 weeks (SD = 17.51 weeks). Time depressed each month decreased over the follow-up period. Posttreatment depressive severity and length of the index episode predicted changes in depression over time. Posttreatment depression severity, personal history of depression, and weeks of treatment in the follow-up were significant predictors of time depressed during follow-up. CONCLUSIONS: IPT resulted in long-term benefits past the termination of acute treatment, even for women who did not initially recover. Though the vast majority of women who did not recover with acute treatment did recover during the follow-up period, continuation of IPT may accelerate the process.

Sexual function in the postpartum period: effects of maternal depression and interpersonal psychotherapy treatment.

Women's sexual functioning in the postpartum period is understudied given its potential impact on women's mental health and their relationships with their partners. The sexual functioning of women with postpartum depression (PPD) in particular is not well characterized. The goals of this study were to examine factors associated with the sexual functioning of postpartum women and to compare the long-term sexual functioning of depressed postpartum women treated with interpersonal psychotherapy with a group of postpartum women who had never been depressed. Depressed (120) and never depressed (56) postpartum women were enrolled. Self-report questionnaires and clinician-rated measures were completed at initial entry to study, immediately post-treatment, and at 6, 12, and 18 months post-treatment. Analyses revealed significant differences in sexual interest between depressed and never depressed postpartum women (t (171) = 11.82, p <0.001). Although sexual interest improved significantly following treatment for depression (t (104) = -3.18, p < 0.01), those women who fully recovered continued to experience less interest (F (2, 140) = 32.24, p < 0.0001) and less sexual satisfaction through 2 years postpartum than never depressed women. These findings suggest that differences in sexual functioning exist between depressed and never depressed postpartum women, even after depressed women are treated and have recovered from their depression. Clinicians should inquire about changes in sexual functioning when treating women with PPD.

Effective treatment for postpartum depression is not sufficient to improve the developing mother-child relationship.

Maternal depression is prevalent, and puts children at risk. Little evidence addresses whether treatment for maternal depression is sufficient to improve child outcomes. An experiment was conducted testing whether psychotherapeutic treatment for mothers, suffering from major depression in the postpartum period, would result in improved parenting and child outcomes. Participants included depressed women randomly assigned to interpersonal psychotherapy (n = 60) or to a waitlist (n = 60), and a nondepressed comparison group (n = 56). At 6 months, depressed mothers were less responsive to their infants, experienced more parenting stress, and viewed their infants more negatively than did nondepressed mothers. Treatment affected only parenting stress, which improved significantly but was still higher than that for nondepressed mothers. Eighteen months later, treated depressed mothers still rated their children lower in attachment security, higher in behavior problems, and more negative in temperament than nondepressed mothers. Initial response to treatment did not predict reduced risk for poor child outcomes. Early maternal negative perceptions of the child predicted negative temperament and behavior problems 18 months after treatment. Treatment for depression in the postpartum period should target the mother-infant relationship in addition to the mothers' depressive symptoms.

Effect of oral vitamin E and C therapy on calcineurin inhibitor levels in heart transplant recipients.

BACKGROUND: A recent prospective trial demonstrated that oral vitamins C and E retard the early progression of transplant-associated coronary arteriosclerosis; as a result, a number of centers have added these agents to their maintenance regimens. This study reviewed the impact of vitamin E and C supplementation on calcineurin inhibitor trough concentrations. METHODS: A retrospective chart review of the first 29 heart transplant patients prescribed anti-oxidant agents was performed. Twenty-two patients taking cyclosporin A (CsA) and 7 patients taking tacrolimus were prescribed vitamin C (500 mg twice a day) and vitamin E (400 IU twice a day). Serum chemistries and drug levels were measured before and after vitamin therapy was initiated. RESULTS: The baseline CsA trough concentration (mean +/- SD) was 137 +/- 39 ng/ml and it declined to 99 +/- 54 ng/ml (p = 0.007) after anti-oxidant therapy was initiated. The average percentage decrease in the CsA trough concentration was 30%. No significant changes were seen in the patients taking tacrolimus. CONCLUSIONS: These data demonstrate that supplementation with the anti-oxidant agents vitamin C and vitamin E decreases CsA concentrations but does not appear to effect tacrolimus concentrations. Although more detailed pharmacokinetic analysis is necessary to clarify the exact mechanism of this interaction, physicians who take care of transplant recipients should be aware that more frequent CsA concentration monitoring is warranted after initiating these anti-oxidant agents.