High-resolution repertoire analysis reveals a major bystander activation of Tfh and Tfr cells.

T follicular helper (Tfh) and regulatory (Tfr) cells are terminally differentiated cells found in germinal centers (GCs), specialized secondary lymphoid organ structures dedicated to antibody production. As such, follicular T (Tfol) cells are supposed to be specific for immunizing antigens, which has been reported for Tfh cells but is debated for Tfr cells. Here, we used high-throughput T cell receptor (TCR) sequencing to analyze the repertoires of Tfh and Tfr cells, at homeostasis and after immunization with self- or foreign antigens. We observed that, whatever the conditions, Tfh and Tfr cell repertoires are less diverse than those of effector T cells and Treg cells of the same tissues; surprisingly, these repertoires still represent thousands of different sequences, even after immunization with a single antigen that induces a 10-fold increase in Tfol cell numbers. Thorough analysis of the sharing and network of TCR sequences revealed that a specific response to the immunizing antigen can only, but hardly, be detected in Tfh cells immunized with a foreign antigen and Tfr cells immunized with a self-antigen. These antigen-specific responses are obscured by a global stimulation of Tfh and Tfr cells that appears to be antigen-independent. Altogether, our results suggest a major bystander Tfol cell activation during the immune response in the GCs.

Online Mindfulness-Based Cognitive Behavioral Therapy Intervention for Youth With Major Depressive Disorders: Randomized Controlled Trial.

BACKGROUND: Approximately 70% of mental health disorders appear prior to 25 years of age and can become chronic when ineffectively treated. Individuals between 18 and 25 years old are significantly more likely to experience mental health disorders, substance dependencies, and suicidality. Treatment progress, capitalizing on the tendencies of youth to communicate online, can strategically address depressive disorders. OBJECTIVE: We performed a randomized controlled trial (RCT) that compared online mindfulness-based cognitive behavioral therapy (CBT-M) combined with standard psychiatric care to standard psychiatric care alone in youth (18-30 years old) diagnosed with major depressive disorder. METHODS: Forty-five participants were randomly assigned to CBT-M and standard care (n=22) or to standard psychiatric care alone (n=23). All participants were provided standard psychiatric care (ie, 1 session per month), while participants in the experimental group received an additional intervention consisting of the CBT-M online software program. Interaction with online workbooks was combined with navigation coaching delivered by phone and secure text messaging. RESULTS: In a two-level linear mixed-effects model intention-to-treat analysis, significant between-group differences were found for the Beck Depression Inventory-II score (difference -8.54, P=.01), Quick Inventory of Depressive Symptoms score (difference -4.94, P=.001), Beck Anxiety Inventory score (difference -11.29, P<.001), and Brief Pain Inventory score (difference -1.99, P=.03), while marginal differences were found for the Five Facet Mindfulness Questionnaire-Nonjudging subscale (difference -2.68, P=.05). CONCLUSIONS: These results confirm that youth depression can be effectively treated with online CBT-M that can be delivered with less geographic restriction. TRIAL REGISTRATION: Clinical Trials.gov NCT03406052; https://www.clinicaltrials.gov/ct2/show/NCT03406052.

Clinical presentation of young people (10-24 years old) with brain tumors: results from the international MOBI-Kids study.

INTRODUCTION: We used data from MOBI-Kids, a 14-country international collaborative case-control study of brain tumors (BTs), to study clinical characteristics of the tumors in older children (10 years or older), adolescents and young adults (up to the age of 24). METHODS: Information from clinical records was obtained for 899 BT cases, including signs and symptoms, symptom onset, diagnosis date, tumor type and location. RESULTS: Overall, 64% of all tumors were low-grade, 76% were neuroepithelial tumors and 62% gliomas. There were more males than females among neuroepithelial and embryonal tumor cases, but more females with meningeal tumors. The most frequent locations were cerebellum (22%) and frontal (16%) lobe. The most frequent symptom was headaches (60%), overall, as well as for gliomas, embryonal and 'non-neuroepithelial' tumors; it was convulsions/seizures for neuroepithelial tumors other than glioma, and visual signs and symptoms for meningiomas. A cluster analysis showed that headaches and nausea/vomiting was the only combination of symptoms that exceeded a cutoff of 50%, with a joint occurrence of 67%. Overall, the median time from first symptom to diagnosis was 1.42 months (IQR 0.53-4.80); it exceeded 1 year in 12% of cases, though no particular symptom was associated with exceptionally long or short delays. CONCLUSIONS: This is the largest clinical epidemiology study of BT in young people conducted so far. Many signs and symptoms were identified, dominated by headaches and nausea/vomiting. Diagnosis was generally rapid but in 12% diagnostic delay exceeded 1 year with none of the symptoms been associated with a distinctly long time until diagnosis.

Postoperative Remote Automated Monitoring and Virtual Hospital-to-Home Care System Following Cardiac and Major Vascular Surgery: User Testing Study.

BACKGROUND: Cardiac and major vascular surgeries are common surgical procedures associated with high rates of postsurgical complications and related hospital readmission. In-hospital remote automated monitoring (RAM) and virtual hospital-to-home patient care systems have major potential to improve patient outcomes following cardiac and major vascular surgery. However, the science of deploying and evaluating these systems is complex and subject to risk of implementation failure. OBJECTIVE: As a precursor to a randomized controlled trial (RCT), this user testing study aimed to examine user performance and acceptance of a RAM and virtual hospital-to-home care intervention, using Philip's Guardian and Electronic Transition to Ambulatory Care (eTrAC) technologies, respectively. METHODS: Nurses and patients participated in systems training and individual case-based user testing at two participating sites in Canada and the United Kingdom. Participants were video recorded and asked to think aloud while completing required user tasks and while being rated on user performance. Feedback was also solicited about the user experience, including user satisfaction and acceptance, through use of the Net Promoter Scale (NPS) survey and debrief interviews. RESULTS: A total of 37 participants (26 nurses and 11 patients) completed user testing. The majority of nurse and patient participants were able to complete most required tasks independently, demonstrating comprehension and retention of required Guardian and eTrAC system workflows. Tasks which required additional prompting by the facilitator, for some, were related to the use of system features that enable continuous transmission of patient vital signs (eg, pairing wireless sensors to the patient) and assigning remote patient monitoring protocols. NPS scores by user group (nurses using Guardian: mean 8.8, SD 0.89; nurses using eTrAC: mean 7.7, SD 1.4; patients using eTrAC: mean 9.2, SD 0.75), overall NPS scores, and participant debrief interviews indicated nurse and patient satisfaction and acceptance of the Guardian and eTrAC systems. Both user groups stressed the need for additional opportunities to practice in order to become comfortable and proficient in the use of these systems. CONCLUSIONS: User testing indicated a high degree of user acceptance of Philips' Guardian and eTrAC systems among nurses and patients. Key insights were provided that informed refinement of clinical workflow training and systems implementation. These results were used to optimize workflows before the launch of an international RCT of in-hospital RAM and virtual hospital-to-home care for patients undergoing cardiac and major vascular surgery.

Development, implementation, and effects of a cancer center's exercise-oncology program.

BACKGROUND: National and international bodies acknowledge the benefit of exercise for people with cancer, yet limited accessibility to related programing remains. Given their involvement in managing the disease, cancer centers can play a central role in delivering exercise-oncology services. The authors developed and implemented a clinically integrated exercise-oncology program at a major cancer center and evaluated its effectiveness and participant experience. METHODS: A hospital-based program with prescribed at-home exercise was developed and accepted referrals over a 42-month period (3.5 years). Implementation was conducted in 2 phases: a pilot phase for women with breast cancer and men with genitourinary cancer and a roll-out phase for all patients with cancer. Enrolled patients were assessed and received an exercise prescription as well as a program manual, resistance bands, and a stability ball from a kinesiologist. Program participation and effectiveness were evaluated up to 48 weeks after the baseline assessment using intention-to-treat analyses. Participants in the roll-out phase were asked to complete a program experience questionnaire at the completion of the 48-week follow-up. RESULTS: In total, 112 participants enrolled in the pilot, and 150 enrolled in the roll-out phase. Program attrition to 48 weeks was 48% and 65% in the pilot and roll-out phases, respectively. In participants who consented to research evaluation of their performance, objective and patient-reported measures of functional capacity improved significantly from baseline in both phases. Participants were highly satisfied with the program. CONCLUSIONS: Despite significant drop-out to program endpoints, our cancer-exercise program demonstrated clinically relevant improvement in functional outcomes and was highly appreciated by participants.

A phase II randomized controlled trial of three exercise delivery methods in men with prostate cancer on androgen deprivation therapy.

BACKGROUND: Existing evidence demonstrates that 1:1 personal training (PT) improves many adverse effects of androgen deprivation therapy (ADT). Whether less resource-intensive exercise delivery models are as effective remains to be established. We determined the feasibility of conducting a multi-center non-inferiority randomized controlled trial comparing PT with supervised group (GROUP) and home-based (HOME) exercise programs, and obtained preliminary efficacy estimates for GROUP and HOME compared to PT on quality of life (QOL) and physical fitness. METHODS: Men with prostate cancer on ADT were recruited from one of two experienced Canadian centres and randomized 1:1:1 to PT, GROUP, or HOME. Randomization was stratified by length of ADT use and site. Participants completed moderate intensity aerobic and resistance exercises 4-5 days per week for 6 months with a target 150 min per week of exercise. Exercise prescriptions were individualized and progressed throughout the trial. Feasibility endpoints included recruitment, retention, adherence, and participant satisfaction. The efficacy endpoints QOL, fatigue, and fitness (VO2 peak, grip strength, and timed chair stands) in GROUP and HOME were compared for non-inferiority to PT. Descriptive analyses were used for feasibility endpoints. Between-group differences for efficacy endpoints were examined using Bayesian linear mixed effects models. RESULTS: Fifty-nine participants (mean age 69.9 years) were enrolled. The recruitment rate was 25.4% and recruitment was slower than projected. Retention was 71.2%. Exercise adherence as measured through attendance was high for supervised sessions but under 50% by self-report and accelerometry. Satisfaction was high and there was no difference in this measure between all three groups. Between-group differences (comparing both GROUP and HOME to PT) were smaller than the minimum clinically important difference on most measures of QOL, fatigue, and fitness. However, two of six outcomes for GROUP and four of six outcomes for HOME had a > 20% probability of being inferior for GROUP. CONCLUSIONS: Feasibility endpoints were generally met. Both GROUP and HOME interventions in men with PC on ADT appeared to be similar to PT for multiple efficacy outcomes, although conclusions are limited by a small sample size and cost considerations have not been incorporated. Efforts need to be targeted to improving recruitment and adherence. A larger trial is warranted. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02046837 . Date of registration: January 20, 2014.

Protocol for a phase III RCT and economic analysis of two exercise delivery methods in men with PC on ADT.

BACKGROUND: Androgen deprivation therapy (ADT) is commonly used to treat prostate cancer. However, side effects of ADT often lead to reduced quality of life and physical function. Existing evidence demonstrates that exercise can ameliorate multiple treatment-related side effects for men on ADT, yet adherence rates are often low. The method of exercise delivery (e.g., supervised group in-centre vs. individual home-based) may be important from clinical and economic perspectives; however, few studies have compared different delivery models. Additionally, long-term exercise adherence and an understanding of predictors of adherence are critical to achieving sustained benefits, but such data are lacking. The primary aim of this multi-centre phase III non-inferiority randomized controlled trial is to determine whether a home-based delivery model is non-inferior to a group-based delivery model in terms of benefits in fatigue and fitness in this population. Two other key aims include examining cost-effectiveness and long-term adherence. METHODS: Men diagnosed with prostate cancer of any stage, starting or continuing on ADT for at least 6 months, fluent in English, and living close to a study centre are eligible. Participants complete five assessments over 12 months (baseline and every 3 months during the 6-month intervention and 6-month follow-up phases), including a fitness assessment and self-report questionnaires. Biological outcomes are collected at baseline, 6, and 12 months. A total of 200 participants will be randomized in a 1:1 fashion to supervised group training or home-based training supported by smartphones, health coaches, and Fitbit technology. Participants are asked to complete 4 to 5 exercise sessions per week, incorporating aerobic, resistance and flexibility training. Outcomes include fatigue, quality of life, fitness measures, body composition, biological outcomes, and program adherence. Cost information will be obtained using patient diary-based self-report and utilities via the EQ-5D. DISCUSSION: To disseminate publicly funded exercise programs widely, clinical efficacy and cost-effectiveness have to be demonstrated. The goals of this trial are to provide these data along with an increased understanding of adherence to exercise among men with prostate cancer receiving ADT. TRIAL REGISTRATION: The trial has been registered at clinicaltrials.gov (Registration # NCT02834416 ). Registration date was June 2, 2016.

Defining and Predicting Pain Volatility in Users of the Manage My Pain App: Analysis Using Data Mining and Machine Learning Methods.

BACKGROUND: Measuring and predicting pain volatility (fluctuation or variability in pain scores over time) can help improve pain management. Perceptions of pain and its consequent disabling effects are often heightened under the conditions of greater uncertainty and unpredictability associated with pain volatility. OBJECTIVE: This study aimed to use data mining and machine learning methods to (1) define a new measure of pain volatility and (2) predict future pain volatility levels from users of the pain management app, Manage My Pain, based on demographic, clinical, and app use features. METHODS: Pain volatility was defined as the mean of absolute changes between 2 consecutive self-reported pain severity scores within the observation periods. The k-means clustering algorithm was applied to users' pain volatility scores at the first and sixth month of app use to establish a threshold discriminating low from high volatility classes. Subsequently, we extracted 130 demographic, clinical, and app usage features from the first month of app use to predict these 2 volatility classes at the sixth month of app use. Prediction models were developed using 4 methods: (1) logistic regression with ridge estimators; (2) logistic regression with Least Absolute Shrinkage and Selection Operator; (3) Random Forests; and (4) Support Vector Machines. Overall prediction accuracy and accuracy for both classes were calculated to compare the performance of the prediction models. Training and testing were conducted using 5-fold cross validation. A class imbalance issue was addressed using a random subsampling of the training dataset. Users with at least five pain records in both the predictor and outcome periods (N=782 users) are included in the analysis. RESULTS: k-means clustering algorithm was applied to pain volatility scores to establish a threshold of 1.6 to differentiate between low and high volatility classes. After validating the threshold using random subsamples, 2 classes were created: low volatility (n=611) and high volatility (n=171). In this class-imbalanced dataset, all 4 prediction models achieved 78.1% (611/782) to 79.0% (618/782) in overall accuracy. However, all models have a prediction accuracy of less than 18.7% (32/171) for the high volatility class. After addressing the class imbalance issue using random subsampling, results improved across all models for the high volatility class to greater than 59.6% (102/171). The prediction model based on Random Forests performs the best as it consistently achieves approximately 70% accuracy for both classes across 3 random subsamples. CONCLUSIONS: We propose a novel method for measuring pain volatility. Cluster analysis was applied to divide users into subsets of low and high volatility classes. These classes were then predicted at the sixth month of app use with an acceptable degree of accuracy using machine learning methods based on the features extracted from demographic, clinical, and app use information from the first month.

Stressing the feedback: attention and cardiac vagal tone during a cognitive stress task.

OBJECTIVES: The present study examined relationships among gaze behaviour and cardiac vagal tone using a novel stress-inducing task. METHODS: Participants' (N = 40) eye movements and heart rate variability (HRV) were measured during an unsolvable computer-based task randomly presenting feedback of "Right" and "Wrong" answers distinctly onscreen after each trial. Subgroups were created on the basis of more frequent eye movements to the right ("Correct"-Attenders; n = 23) or wrong ("Incorrect"-Attenders; n = 17) areas onscreen. RESULTS: Correct-Attenders maintained HRV from baseline to the stress task. In contrast, Incorrect-Attenders spent significantly more time viewing "Wrong" feedback, exhibited a reduction in HRV during the stress condition (p < .01), and were more likely to negatively self-evaluate performance. CONCLUSIONS: Results demonstrate that pervasive attention to negative feedback ("Wrong") elicits perseverative stress and negative self-evaluations among university students. This study highlights the potential for studying attentional biases and emotional distress through combined measures of gaze behaviour and cardiac vagal tone.

Taxonomy for colorectal cancer screening promotion: Lessons from recent randomized controlled trials.

OBJECTIVE: To derive a taxonomy for colorectal cancer screening that advances Randomized Controlled Trials (RCTs) and screening uptake. DESIGN: Detailed publication review, multiple interviews with principal investigators (PIs) and collaboration with PIs as co-authors produced a CRCS intervention taxonomy. Semi-structured interview questions with PIs (Drs. Inadomi, Myers, Green, Gupta, Jerant and Ritvo) yielded details about trial conduct. Interview comparisons led to an iterative process informing serial interviews until a consensus was obtained on final taxonomy structure. RESULTS: These taxonomy headings (Engagement Sponsor, Population Targeted, Alternative Screening Tests, Delivery Methods, and Support for Test Performance (EPADS)) were used to compare studies. Exemplary insights emphasized: 1) direct test delivery to patients; 2) linguistic-ethnic matching of staff to minority subjects; and 3) authorization of navigators to schedule or refer for colonoscopies and/or distribute stool blood tests during screening promotion. CONCLUSION: PIs of key RCTs (2012-2015) derived a CRCS taxonomy useful in detailed examination of CRCS promotion and design of future RCTs.

The validity of the SF-12 and SF-6D instruments in people living with HIV/AIDS in Kenya.

BACKGROUND: Health-related quality of life (HRQoL) and health state utility value (HSUV) measurements are vital components of healthcare clinical and economic evaluations. Accurate measurement of HSUV and HRQoL require validated instruments. The 12-item Short-Form Health Survey (SF-12) is one of few instruments that can evaluate both HRQoL and HSUV, but its validity has not been assessed in people living with HIV/AIDS (PLWHA) in east Africa, where the burden of HIV is high. METHODS: This cross-sectional study used baseline data from a randomized trial involving PLWHA in Kenya. Data included responses from a translated and adapted SF-12 survey as well as key demographic and clinical data. Construct validity of the survey was examined by testing the SF-12's ability to distinguish between groups known in advance to have differences in their health based on their disease severity. We classified disease severity based on established definitions from the US Center for Disease Control (CDC) and WHO, as well as a previously studied viral load threshold. T-tests and ANOVA were used to test for differences in HRQoL and HSUV scores. Area under the receive operator curve (AUC) was used to test the discriminative ability of the HRQoL and HSUV instruments. RESULTS: Differences in physical component scores met the minimum clinically important difference among participants with more advanced HIV when defined by CD4 count (4.3 units) and WHO criteria (compared to stage 1, stages 2, 3 and 4 were 2.0, 7.2 and 9.8 units lower respectively). Mental score differences met the minimum clinically important difference between WHO stage 1 and stage 4 patients (4.4). Differences in the HSUV were statistically lower in more advanced HIV by all three definitions of severity. The AUC showed poor to weak discriminatory ability in most analyses, but had fair discriminatory ability between WHO clinical stage 1 and clinical stage 4 individuals (AUC = 0.71). CONCLUSION: Our findings suggest that the Kiswahili translated and adapted version of the SF-12 could be used as an assessment tool for physical health, mental health and HSUV for Kiswahili-speaking PLHWA. TRIAL REGISTRATION: Clinical trials.gov identifier: NCT00830622 . Registered 26 January 2009.

The mental health status of ethnocultural minorities in Ontario and their mental health care.

BACKGROUND: Mental disorders are a leading cause of disability and early mortality. The objective of this study was to describe and compare psychosocial indicators and mental health service use among ethnoculturally-diverse Ontarians. METHODS: This is a cross-sectional analysis of the Ontario Health Study pilot investigation. Residents were mailed an invitation to one of 3 assessment centres (urban, rural and northern sites) from March 2009 to July 2010. Participants had an interview with a nurse and completed a questionnaire on a touchscreen kiosk. The questionnaire included sociodemographic items, and scales assessing symptoms of depressive symptoms (CES-D) and anxiety (GAD-7), social support (Lubben Social Network Scale), stressful life events, and mental health service use. RESULTS: Eight thousand two hundred thirty-five residents participated, among whom 6652 (82.4 %) self-reported their ethnocultural background as White, 225 (2.8 %) as South Asian, 222 (2.8 %) East Asian, 214 (2.7 %) Southeast Asian, 197 (2.4 %) Black, and 28 (0.3 %) as Aboriginal. Based on their sociodemographic characteristics, participants from these ethnocultural minority groups were matched to White participants. Black participants reported significantly greater stressful life events than White participants (p = .04), particularly death (p < .05), divorce (p = .002) and financial difficulties (p < .001). East Asian participants reported significantly less social support than their White counterparts (p < .001), and this was not confounded by measurement variance. Mental health service use was significantly lower in all ethnocultural minorities except Aboriginals, when compared to White participants (p = .001). CONCLUSIONS: There is a high burden of psychosocial distress in several preponderant ethnocultural minorities in Ontario; many of whom are not accessing available mental health services.

A phase II RCT and economic analysis of three exercise delivery methods in men with prostate cancer on androgen deprivation therapy.

BACKGROUND: Androgen deprivation therapy is commonly used to treat prostate cancer, the most common visceral cancer in men. However, various side effects often worsen physical functioning and reduce well-being among men on this treatment. Based on existing evidence, both resistance and aerobic training provide benefits for this population yet adherence rates are often low. The method of exercise delivery (supervised in-center or home-based) may be important, yet few studies have compared different models. Additionally, long-term exercise adherence is critical to achieve sustained benefits but long-term adherence data and predictors of adherence are lacking. The primary aim of this phase II, non-inferiority randomized controlled trial is to determine whether three exercise training delivery models are equivalent in terms of benefits in quality of life and physical fitness in this population. Secondary aims include examination of long-term adherence and cost-effectiveness. DESIGN: Men diagnosed with prostate cancer, starting or continuing on androgen deprivation therapy for at least 6 months, fluent in English, and living close to one of two experienced Canadian study centers are eligible. Participants complete five assessments over one year, including a fitness assessment and self-report questionnaires. Socio-demographic and clinical data collection occur at baseline, bone mineral density testing at two time points, and blood work is performed at three time points. Participants are randomized in a 1:1:1 fashion to supervised personal training, supervised group training, or home-based smartphone- and health coach-supported training. Each participant receives a detailed exercise manual, including illustrations of exercises and safety precautions. Participants are asked to complete 4 to 5 exercise sessions per week, incorporating aerobic, resistance and flexibility training. Participant intensity levels will be monitored. The intervention duration is 6 months, with 6 months additional follow-up. Outcomes include: body composition, fitness testing, quality of life and fatigue, biological outcomes, and program adherence. Cost information will be obtained using patient diary-based self-report. DISCUSSION: The goals of this study are to gain a better understanding of health benefits and costs associated with commonly used yet currently not compared exercise delivery models as well as an increased understanding of adherence to exercise. TRIAL REGISTRATION: The trial has been registered at clinicaltrials.gov (Registration # NCT02046837), registered January 20(th), 2014.

Functional capacity and heart rate response: associations with nocturnal hypertension.

BACKGROUND: Absences of normative, 10-20 % declines in blood pressure (BP) at night, termed nocturnal non-dipping, are linked to increased cardiovascular mortality risks. Current literature has linked these absences to psychological states, hormonal imbalance, and disorders involving hyper-arousal. This study focuses on evaluating associations between nocturnal non-dipping and indices of functional cardiac capacity and fitness. METHODS: The current study was a cross-sectional evaluation of the associations between physical capacity variables e.g. Metabolic Equivalent (MET) and Maximum Heart Rate (MHR), Heart rate reserve (HRR), and degree of reduction in nocturnal systolic blood pressure (SBP) or diastolic blood pressure (DBP), also known as 'dipping'. The study sample included 96 cardiac patient participants assessed for physical capacity and ambulatory blood pressure monitoring. In addition to evaluating differences between groups on nocturnal BP 'dipping', physical capacity, diagnoses, and medications, linear regression analyses were used to evaluate potential associations between nocturnal SBP and DBP 'dipping', and physical capacity indices. RESULTS: 45 males and 14 females or 61.5 % of 96 consented participants met criteria as non-dippers (<10 % drop in nocturnal BP). Although non-dippers were older (p = .01) and had a lower maximum heart rate during the Bruce stress test (p = .05), dipping was only significantly associated with Type 2 Diabetes co-morbidity and was not associated with type of medication. Within separate linear regression models controlling for participant sex, MHR (ß = 0.26, p = .01, R(2) = .06), HRR (ß = 0. 19, p = .05, R(2) = .05), and METs (ß = 0.21, p = .04, R(2) = .04) emerged as significant but small predictors of degree of nighttime SBP dipping. Similar relationships were not observed for DBP. CONCLUSIONS: Since the variables reflecting basic heart function and fitness (MHR and METs), did not account for appreciable variances in nighttime BP, nocturnal hypertension appears to be a complex, multi-faceted phenomena.

A pilot randomized trial of conventional versus advanced pelvic floor exercises to treat urinary incontinence after radical prostatectomy: a study protocol.

BACKGROUND: Radical prostatectomy is the most common and effective treatment for localized prostate cancer. Unfortunately, radical prostatectomy is associated with urinary incontinence and has a significant negative impact on quality of life. Pelvic floor exercises are the most common non-invasive management strategy for urinary incontinence following radical prostatectomy; however, studies provide inconsistent findings regarding their efficacy. One potential reason for sub-optimal efficacy of these interventions is the under-utilization of regional muscles that normally co-activate with the pelvic floor, such as the transverse abdominis, rectus abdominis, and the diaphragm. Two novel approaches to improve urinary continence recovery are 'Pfilates' and 'Hypopressives' that combine traditional pelvic floor exercises with the activation of additional supportive muscles. Our study will compare an advanced pelvic floor exercise training program that includes Pfilates and Hypopressives, to a conventional pelvic floor exercises regimen for the treatment of post-radical prostatectomy urinary incontinence. METHODS/DESIGN: This is a pilot, randomized controlled trial of advanced pelvic floor muscle training versus conventional pelvic floor exercises for men with localized prostate cancer undergoing radical prostatectomy. Eighty-eight men who will be undergoing radical prostatectomy at hospitals in Toronto, Canada will be recruited. Eligible participants must not have undergone androgen deprivation therapy and/or radiation therapy. Participants will be randomized 1:1 to receive 26 weeks of the advanced or conventional pelvic floor exercise programs. Each program will be progressive and have comparable exercise volume. The primary outcomes are related to feasibility for a large, adequately powered randomized controlled trial to determine efficacy for the treatment of urinary incontinence. Feasibility will be assessed via recruitment success, participant retention, outcome capture, intervention adherence, and prevalence of adverse events. Secondary outcomes of intervention efficacy include measures of pelvic floor strength, urinary incontinence, erectile function, and quality of life. Secondary outcome measures will be collected prior to surgery (baseline), and at 2, 6, 12, 26-weeks post-operatively. DISCUSSION: Pfilates and Hypopressives are novel approaches to optimizing urinary function after radical prostatectomy. This trial will provide the foundation of data for future, large-scale trials to definitively describe the effect of these advanced pelvic floor exercise modalities compared to conventional pelvic floor exercise regimes for men with prostate cancer undergoing radical prostatectomy TRIAL REGISTRATION: Clinicalstrials.gov Identifier: NCT02233608.

Health Coaching Reduces HbA1c in Type 2 Diabetic Patients From a Lower-Socioeconomic Status Community: A Randomized Controlled Trial.

BACKGROUND: Adoptions of health behaviors are crucial for maintaining good health after type 2 diabetes mellitus (T2DM) diagnoses. However, adherence to glucoregulating behaviors like regular exercise and balanced diet can be challenging, especially for people living in lower-socioeconomic status (SES) communities. Providing cost-effective interventions that improve self-management is important for improving quality of life and the sustainability of health care systems. OBJECTIVE: To evaluate a health coach intervention with and without the use of mobile phones to support health behavior change in patients with type 2 diabetes. METHODS: In this noninferiority, pragmatic randomized controlled trial (RCT), patients from two primary care health centers in Toronto, Canada, with type 2 diabetes and a glycated hemoglobin/hemoglobin A1c (HbA1c) level of ≥7.3% (56.3 mmol/mol) were randomized to receive 6 months of health coaching with or without mobile phone monitoring support. We hypothesized that both approaches would result in significant HbA1c reductions, although health coaching with mobile phone monitoring would result in significantly larger effects. Participants were evaluated at baseline, 3 months, and 6 months. The primary outcome was the change in HbA1c from baseline to 6 months (difference between and within groups). Other outcomes included weight, waist circumference, body mass index (BMI), satisfaction with life, depression and anxiety (Hospital Anxiety and Depression Scale [HADS]), positive and negative affect (Positive and Negative Affect Schedule [PANAS]), and quality of life (Short Form Health Survey-12 [SF-12]). RESULTS: A total of 138 patients were randomized and 7 were excluded for a substudy; of the remaining 131, 67 were allocated to the intervention group and 64 to the control group. Primary outcome data were available for 97 participants (74.0%). While both groups reduced their HbA1c levels, there were no significant between-group differences in change of HbA1c at 6 months using intention-to-treat (last observation carried forward [LOCF]) (P=.48) or per-protocol (P=.83) principles. However, the intervention group did achieve an accelerated HbA1c reduction, leading to a significant between-group difference at 3 months (P=.03). This difference was reduced at the 6-month follow-up as the control group continued to improve, achieving a reduction of 0.81% (8.9 mmol/mol) (P=.001) compared with a reduction of 0.84% (9.2 mmol/mol)(P=.001) in the intervention group. Intervention group participants also had significant decreases in weight (P=.006) and waist circumference (P=.01) while controls did not. Both groups reported improvements in mood, satisfaction with life, and quality of life. CONCLUSIONS: Health coaching with and without access to mobile technology appeared to improve glucoregulation and mental health in a lower-SES, T2DM population. The accelerated improvement in the mobile phone group suggests the connectivity provided may more quickly improve adoption and adherence to health behaviors within a clinical diabetes management program. Overall, health coaching in primary care appears to lead to significant benefits for patients from lower-SES communities with poorly controlled type 2 diabetes. TRIAL REGISTRATION: ClinicalTrials.gov NCT02036892; http://clinicaltrials.gov/ct2/show/NCT02036892 (Archived by WebCite at http://www.webcitation.org/6b3cJYJOD).

Exploring gay couples' experience with sexual dysfunction after radical prostatectomy: a qualitative study.

This exploratory study examines the experience of three gay couples managing sexual dysfunction as a result of undergoing a radical prostatectomy. Semi-structured interviews were conducted as part of a larger study at an urban hospital in Toronto, Ontario, Canada. Interview transcripts were transcribed verbatim, and analyzed using interpretative phenomenological analysis. The authors clustered 18 subordinate themes under 3 superordinate themes: (a) acknowledging change in sexual experience (libido, erectile function, sexual activity, orgasmic function); (b) accommodating change in sexual experience (strategies: emphasizing intimacy, embracing plan B, focus on the other; barriers: side-effect concerns, loss of naturalness, communication breakdown, failure to initiate, trial and failure, partner confounds); and (c) accepting change in sexual experience (indicators: emphasizing health, age attributions, finding a new normal; barriers: uncertain outcomes, treatment regrets). Although gay couples and heterosexual couples share many similar challenges, we discovered that gay men have particular sexual roles and can engage in novel accommodation practices, such as open relationships, that have not been noted in heterosexual couples. All couples, regardless of their level of sexual functioning, highlighted the need for more extensive programming related to sexual rehabilitation. Equitable rehabilitative support is critical to assist homosexual couples manage distress associated with prostatectomy-related sexual dysfunction.

Conceptualizing global health-related quality of life in bladder cancer.

PURPOSE: Patients' values for health outcomes are central to treatment decisions in bladder cancer (BCa). An instrument incorporating the expressed preferences of BCa patients, as measured by utility, can inform clinical guidelines, resource allocation and policy decisions. Developing this instrument requires a formal conceptual framework summarizing the important domains comprising global health-related quality of life (HRQOL) in BCa. METHODS: We performed a systematic literature search on the HRQOL effects of BCa and its treatments to generate initial items in Medline, Embase, CINAHL and PsychInfo up to January 2013. Thematic synthesis was used to group related items into overarching themes (domains) and create a provisional conceptual framework. In focus groups, 12 BCa experts and 47 BCa patients with diverse clinical histories generated further items to inform the final conceptual framework. RESULTS: We retrieved 1,275 citations and reviewed 170 full-text publications. One hundred and sixty-nine items were extracted into 12 domains. Study investigators used the findings from the focus groups to confirm the domains and condense the list to 83 clinically important items. Functional limitations in work, travel, social interaction and sleep lowered HRQOL in many domains. The final conceptual framework included BCa-specific (urinary, sexual, bowel, body image) and generic domains (pain, vigor, social, psychological, sleep, functional, family relationship, medical care relationship). CONCLUSIONS: A conceptual framework including 12 domains can serve as the foundation for the development of an instruments measuring global HRQOL in BCa and in particular, one that can measure patient preferences and generate utilities.

Who are the under- and never-screened for cancer in Ontario: a qualitative investigation.

BACKGROUND: Observed breast, cervical and colon cancer screening rates are below provincial targets for the province of Ontario, Canada. The populations who are under- or never-screened for these cancers have not been described at the Ontario provincial level. Our objective was to use qualitative methods of inquiry to explore who are the never- or under-screened populations of Ontario. METHODS: Qualitative data were collected from two rounds of focus group discussions conducted in four communities selected using maps of screening rates by dissemination area. The communities selected were archetypical of the Ontario context: urban, suburban, small city and rural. The first phase of focus groups was with health service providers. The second phase of focus groups was with community members from the under- and never-screened population. Guided by a grounded theory methodology, data were collected and analyzed simultaneously to enable the core and related concepts about the under- and never-screened to emerge. RESULTS: The core concept that emerged from the data is that the under- and never-screened populations of Ontario are characterized by diversity. Group level characteristics of the under- and never-screened included: 1) the uninsured (e.g., Old Order Mennonites and illegal immigrants); 2) sexual abuse survivors; 3) people in crisis; 4) immigrants; 5) men; and 6) individuals accessing traditional, alternative and complementary medicine for health and wellness. Under- and never-screened could have one or multiple group characteristics. CONCLUSION: The under- and never-screened in Ontario comprise a diversity of groups. Heterogeneity within and intersectionality among under- and never-screened groups adds complexity to cancer screening participation and program planning.

Smartphone-enabled health coach intervention for people with diabetes from a modest socioeconomic strata community: single-arm longitudinal feasibility study.

BACKGROUND: Lower socioeconomic strata (SES) populations have higher chronic disease risks. Smartphone-based interventions can support adoption of health behaviors that may, in turn, reduce the risks of type 2 diabetes-related complications, overcoming the obstacles that some patients may have with regular clinical contact (eg, shiftwork, travel difficulties, miscommunication). OBJECTIVE: The intent of the study was to develop and test a smartphone-assisted intervention that improves behavioral management of type 2 diabetes in an ethnically diverse, lower SES population within an urban community health setting. METHODS: This single-arm pilot study assessed a smartphone application developed with investigator assistance and delivered by health coaches. Participants were recruited from the Black Creek Community Health Centre in Toronto and had minimal prior experience with smartphones. RESULTS: A total of 21 subjects consented and 19 participants completed the 6-month trial; 12 had baseline glycosylated hemoglobin (HbA1c) levels >7.0% and these subjects demonstrated a mean reduction of 0.43% (SD 0.63) (P<.05) with minimal changes in medication. CONCLUSIONS: This project supported the feasibility of smartphone-based health coaching for individuals from lower SES with minimal prior smartphone experience.