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1.
Diabetes ; 2021 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-33479057

RESUMO

Regulatory T cell (Treg) insufficiency licenses the destruction of insulin-producing pancreatic ß cells by auto-reactive effector T cells (Teffs), causing spontaneous autoimmune diabetes in non-obese diabetic (NOD) mice. We investigated the contribution to diabetes of the TCR repertoires of naive regulatory T cells (nTregs), activated/memory Tregs (amTregs), and CD4+ Teffs from prediabetic NOD mice and normal C57BL/6 (B6) mice. NOD mice amTreg and Teff repertoire diversity was unexpectedly higher than that of B6 mice. This was due to the presence of highly expanded clonotypes in B6 amTregs and Teffs that were largely lost in their NOD counterparts. IL-2 administration to NOD mice restored such amTreg clonotype expansions and prevented diabetes development. In contrast, IL-2 administration only led to few or no clonotype expansions in nTregs and Teffs, respectively. Noteworthily, IL-2 expanded amTreg and nTreg clonotypes were markedly enriched in islet-antigen specific TCRs. Altogether, our results highlight the link between a reduced clonotype expansion within the activated Treg repertoire and the development of an autoimmune disease. They also indicate that the repertoire of amTregs is amenable to rejuvenation by IL-2.Non-obese diabetic (NOD) mice spontaneously develop autoimmune diabetes due to the destruction of insulin-producing ß cells by auto-reactive CD4+ and CD8+ T cells (1). Diabetes susceptibility in NOD mice is attributed to genetic defects encoded by the insulin-dependent diabetes (idd) loci including over 40 genes, among which the MHC class II and interleukin-2 (IL-2) genes have major contributions to the pathophysiological immune response leading to diabetes (2). The unique I-Ag7 MHC-II molecule expressed by NOD mice has been reported to bind certain peptides with low affinity, thus impairing the thymocyte negative selection process (3,4). Reduced IL-2 production by activated effector T cells (Teffs) was found in NOD mice and linked to an impairment of Treg numbers and functionality (5-7). An increased diabetes incidence was observed in NOD mice bearing an IL-2 alpha receptor subunit with reduced affinity for IL-2, which was associated with a Treg but not a Teff defect (8). Likewise, the administration of low-dose IL-2 to NOD mice promotes Treg expansion and activation, prevents diabetes onset and even cures diabetic mice (9, 10). Thus, the altered tolerance promoting diabetes in NOD mice could be the result of (i) a defect in thymic selection of Treg and Teff T-cell receptor (TCR) repertoires and/or (ii) an altered Treg fitness due to IL-2 deprivation.Previous studies of the TCR repertoires of NOD mice and type 1 diabetes patients yielded inconsistent results. Some studies showed a restricted TRBV and TRBJ chain usage by CD4+ T cells from pancreatic islets and pancreatic lymph nodes (PLN), indicating that overrepresented islet-specific TCRs preferentially express certain TRBVJ genes (11-13). Conversely, others showed a rather diverse gene usage among islet-infiltrating CD4+ T cells in NOD mice (14), including islet-infiltrating memory CD4+ T cells (15, 16), and no common highly used TRBVBJ combinations in T cells from PLN of type 1 diabetes patients (17). Moreover, NOD Tregs were found to have a restricted TRA repertoire and limited overlap with thymic CD4+ T cells (18, 19), while we found similar TRB diversity between NOD peripheral Tregs and Teffs (20). These somehow conflicting results can be explained by the fact that (i) most of these studies were performed on unsorted CD4+ T cells and thus did not distinguish between regulatory and effector populations and/or (ii) most Treg repertoire analyses were done on a limited fraction of the repertoire by using TCR transgenic NOD mice or by focusing on few rearrangements (18, 19). More importantly, most studies have overlooked the existence of regulatory T cell subsets. Indeed, we previously showed that Tregs could be phenotypically divided into CD4+Foxp3+CD44low CD62Lhigh naïve Tregs (nTregs) that have a low turnover, and CD4+Foxp3+CD44highCD62Llow activated/memory Tregs (amTregs) that have a very rapid turnover due to their interaction with their cognate antigens (21). In the healthy B6 mouse background, we showed that amTregs are enriched in deep tissue-draining lymph nodes (LNs) and are characterized by unique clonotype expansions (22). Moreover, we showed little overlap between amTreg and nTreg TRB repertoires (22). Thus, studying amTreg and nTreg TCR repertoires without separating them may be confounding.Here we compared the TCR repertoire of splenic amTregs, nTregs and Teffs of prediabetic NOD and normal B6 mice to investigate whether and how an altered TCR repertoire contributes to diabetes. We found that NOD amTregs have an unexpectedly more diverse repertoire than that of B6 mice, due to the absence of expanded clonotypes. Treatment of prediabetic NOD mice with IL-2, which prevents diabetes occurrence, restored the expansion of clonotypes that are preferentially diabetes-reactive. Thus, the TCR repertoire of amTregs is altered by an IL-2 insufficiency, which instigates diabetes development in NOD mice, and is amenable to therapeutic recovery.

2.
JMIR Ment Health ; 2020 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-33264098

RESUMO

BACKGROUND: Background: University students are experiencing higher levels of distress and mental health disorders. In addressing mental health needs, web-based interventions have shown increasing promise to overcome geographic distances and high student-to-counselor ratios, leading to the potential for wider implementation. The Mindfulness Virtual Community (MVC) program, a web based program, guided by mindfulness and cognitive behavioural therapy principles, is among efforts aimed at effectively and efficiently reducing symptoms of depression, anxiety, and perceived stress in students. OBJECTIVE: Objective: This study's aim was to evaluate the efficacy of an 8-week MVC program in reducing depression, anxiety, and perceived stress (primary outcomes), and improving mindfulness (secondary outcome) in undergraduate students at a large Canadian university. Guided by two prior randomized controlled trials (RCTs) that each demonstrated efficacy when conducted during regular university operations, the current study coincided with a university-wide labour strike. Nonetheless, the students' response to an online mental health program on a disrupted campus can provide useful information for anticipating the impact of other disruptions, including those related to COVID-19, currently and in a foreseeable future. METHODS: Methods: In this parallel arm randomized controlled trial (RCT), 154 students were randomly allocated to an 8-week MVC intervention (n= 76) or a waitlist control (WLC) condition (n= 78). The MVC intervention included (1) educational and mindfulness video modules, (2) anonymous peer-peer discussions, and (3) anonymous, group-based, professionally-guided, 20-min videoconferences. Study outcomes were evaluated at baseline and at 8-week follow-up using: Patient Health Questionnaire-9 (PHQ-9), the Beck Anxiety Inventory (BAI), the Perceived Stress Scale (PSS), and the Five Facets Mindfulness Questionnaire Short Form (FFMQ-SF). Generalized estimation equations with an AR(1) covariance structure were used to evaluate the impact of intervention, with outcome evaluations performed on both an intention to treat (ITT) and per protocol (PP) basis. RESULTS: Results: Participants (n= 154) included 35 males and 117 females with a mean age of 23.1 years. There were no statistically significant differences at baseline between MVC and WLC on demographics and psychological characteristics, indicating similar demographic and psychological characteristics across the MVC-WLC groups. Results under both ITT and PP approaches indicated that except for PSS (ITT: ß= -2.31, P= .03; PP: ß= -2.38, P= .03), there were no statistically significant between group differences in PHQ-9 (ITT: ß= -0.44, P= 0.64; PP: ß= -0.62, P= .053), BAI (ITT: ß= -2.06, P= .31; PP: ß= -2.32, P= .27), and FFMQ-SF (ITT: ß= 1.33, P= .43; PP: ß= 1.44, P= .41) compared to WLC. CONCLUSIONS: Conclusions: During a university labour strike, the MVC program led to statistically significant reductions in PSS compared to WLC, but no other significant between group differences. Comparisons with previous cycles of intervention testing, undertaken during non-disrupted university operations, when efficacy was demonstrated, are discussed. CLINICALTRIAL: Trial Registration: International Standard Randomized Controlled Trial Number ISRCTN92827275; https://www.isrctn.com/ISRCTN92827275.

4.
JMIR Ment Health ; 7(7): e18595, 2020 07 17.
Artigo em Inglês | MEDLINE | ID: mdl-32554380

RESUMO

BACKGROUND: A student mental health crisis is increasingly acknowledged and will only intensify with the COVID-19 crisis. Given accessibility of methods with demonstrated efficacy in reducing depression and anxiety (eg, mindfulness meditation and cognitive behavioral therapy [CBT]) and limitations imposed by geographic obstructions and localized expertise, web-based alternatives have become vehicles for scaled-up delivery of benefits at modest cost. Mindfulness Virtual Community (MVC), a web-based program informed by CBT constructs and featuring online videos, discussion forums, and videoconferencing, was developed to target depression, anxiety, and experiences of excess stress among university students. OBJECTIVE: The aim of this study was to assess the effectiveness of an 8-week web-based mindfulness and CBT program in reducing symptoms of depression, anxiety, and stress (primary outcomes) and increasing mindfulness (secondary outcome) within a randomized controlled trial (RCT) with undergraduate students at a large Canadian university. METHODS: An RCT was designed to assess undergraduate students (n=160) who were randomly allocated to a web-based guided mindfulness-CBT condition (n=80) or to a waitlist control (WLC) condition (n=80). The 8-week intervention consisted of a web-based platform comprising (1) 12 video-based modules with psychoeducation on students' preidentified life challenges and applied mindfulness practice; (2) anonymous peer-to-peer discussion forums; and (3) anonymous, group-based, professionally guided 20-minute live videoconferences. The outcomes (depression, anxiety, stress, and mindfulness) were measured via an online survey at baseline and at 8 weeks postintervention using the Patient Health Questionnaire-9 (PHQ9), the Beck Anxiety Inventory (BAI), the Perceived Stress Scale (PSS), and the Five Facets Mindfulness Questionnaire Short Form (FFMQ-SF). Analyses employed generalized estimation equation methods with AR(1) covariance structures and were adjusted for possible covariates (gender, age, country of birth, ethnicity, English as first language, paid work, unpaid work, relationship status, physical exercise, self-rated health, and access to private mental health counseling). RESULTS: Of the 159 students who provided T1 data, 32 were males and 125 were females with a mean age of 22.55 years. Participants in the MVC (n=79) and WLC (n=80) groups were similar in sociodemographic characteristics at T1 with the exception of gender and weekly hours of unpaid volunteer work. At postintervention follow-up, according to the adjusted comparisons, there were statistically significant between-group reductions in depression scores (ß=-2.21, P=.01) and anxiety scores (ß=-4.82, P=.006), and a significant increase in mindfulness scores (ß=4.84, P=.02) compared with the WLC group. There were no statistically significant differences in perceived stress for MVC (ß=.64, P=.48) compared with WLC. CONCLUSIONS: With the MVC intervention, there were significantly reduced depression and anxiety symptoms but no significant effect on perceived stress. Online mindfulness interventions can be effective in addressing common mental health conditions among postsecondary populations on a large scale, simultaneously reducing the current burden on traditional counseling services. TRIAL REGISTRATION: ISRCTN Registry ISRCTN12249616; http://www.isrctn.com/ISRCTN12249616.

5.
J Geriatr Oncol ; 11(7): 1074-1077, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32143995

RESUMO

BACKGROUND: Androgen deprivation therapy (ADT) for prostate cancer (PCa) is associated with metabolic perturbations and declines in bone mineral density (BMD). Exercise interventions provide multiple health benefits to older men on ADT; however, their effect on metabolic biomarkers and BMD remains unclear. METHODS: A secondary analysis of a phase II randomized controlled trial was conducted to assess the effect of a six-month moderate-intensity aerobic and resistance exercise program on metabolic biomarkers and BMD in men on ADT. Participants were randomized to three different exercise delivery models: personal training; supervised group exercise; or home-based exercise. Analysis of metabolic biomarkers (lipid profile and glucose) was conducted at baseline, six and twelve months. BMD of the lumbar spine, femoral neck and hip were assessed at baseline and twelve months. Both within- and between-group analyses of change scores adjusted for baseline values were performed. RESULTS: Forty-eight men (mean age 69.8y) were enrolled. Baseline values of metabolic biomarkers and BMD were comparable between groups and the three groups were combined for the primary analysis. At six months, no changes in metabolic biomarkers were found; however, at twelve months low-density lipoprotein (+0.28 mmol/L; 95%CI, 0.04 to 0.51) and total cholesterol (+0.31 mmol/L; 95%CI, 0.00 to 0.61) were significantly increased from baseline. No changes were found in BMD. In a secondary between-group analysis, no improvements were observed for any metabolic biomarker or BMD measurement. CONCLUSIONS: Different exercise prescription parameters (modality and intensity) or combined diet/exercise interventions may be needed to foster favorable metabolic and skeletal adaptations during ADT.

6.
J Neurooncol ; 147(2): 427-440, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32124185

RESUMO

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.

7.
J Med Internet Res ; 22(3): e15548, 2020 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-32186521

RESUMO

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.


Assuntos
Doenças Cardiovasculares/cirurgia , Serviços de Assistência Domiciliar/normas , Hospitais/normas , Monitorização Fisiológica/métodos , Interface Usuário-Computador , Idoso , Feminino , Humanos , Masculino , Período Pós-Operatório
8.
JMIR Ment Health ; 7(2): e15520, 2020 02 18.
Artigo em Inglês | MEDLINE | ID: mdl-32074061

RESUMO

BACKGROUND: Innovative interventions are needed to address the increasing mental health needs of university students. Given the demonstrated anxiolytic and antidepressant benefits of mindfulness training, we developed an 8-week, Web-based Mindfulness Virtual Community (MVC) intervention informed by cognitive behavioral therapy (CBT) constructs. OBJECTIVE: This study investigated the efficacy of the MVC intervention in reducing symptoms of depression, anxiety, and stress among undergraduate students in Toronto, Canada. The secondary outcomes included quality of life, life satisfaction, and mindfulness. METHODS: The first 4 weeks of the full MVC intervention (F-MVC) comprised: (1) 12 video-based modules with psycho-education on students' preidentified stressful topics and topically applied mindfulness practice; (2) anonymous peer-to-peer discussion forums; and (3) anonymous, group-based, professionally guided, 20-min live videoconferences. The second 4 weeks of F-MVC involved access only to video-based modules. The 8-week partial MVC (P-MVC) comprised 12 video-based modules. A randomized controlled trial was conducted with 4 parallel arms: F-MVC, P-MVC, waitlist control (WLC), and group-based face-to-face CBT; results for the latter group are presented elsewhere. Students recruited through multiple strategies consented and were randomized: WLC=40; F-MVC=40, P-MVC=39; all learned about allocation after consenting. The online surveys at baseline (T1), 4 weeks (T2), and 8 weeks (T3) included the Patient Health Questionnaire-9 item, Beck Anxiety Inventory, Perceived Stress Scale, Quality of Life Scale, Brief Multi-Dimensional Students Life Satisfaction Scale, and Five-Facet Mindfulness Questionnaire. Analyses employed generalized estimation equation methods with AR(1) covariance structures and were adjusted for possible confounders (gender, age, birth country, paid work, unpaid work, physical activities, self-rated health, and mental health counseling access). RESULTS: Of the 113 students who provided T1 data, 28 were males and 85 were females with a mean age of 24.8 years. Participants in F-MVC (n=39), P-MVC (n=35), and WLC (n=39) groups were similar in sociodemographic characteristics at T1. At T3 follow-up, per adjusted comparisons, there were statistically significant reductions in depression scores for F-MVC (score change -4.03; P<.001) and P-MVC (score change -4.82; P<.001) when compared with WLC. At T3, there was a statistically significant reduction in anxiety scores only for P-MVC (score change -7.35; P=.01) when compared with WLC. There was a statistically significant reduction in scores for perceived stress for both F-MVC (score change -5.32; P<.001) and P-MVC (score change -5.61; P=.005) compared with WLC. There were statistically significant changes at T3 for quality of life and mindfulness for F-MVC and P-MVC vs WLC but not for life satisfaction. CONCLUSIONS: Internet-based mindfulness CBT-based interventions, such as F-MVC and P-MVC, can result in significant reductions in symptoms of depression, anxiety, and stress in a student population. Future research with a larger sample from multiple universities would more precisely test generalizability. TRIAL REGISTRATION: International Standard Randomized Controlled Trial Number ISRCTN92827275; https://www.isrctn.com/ISRCTN92827275.

9.
PM R ; 12(1): 55-63, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-30873696

RESUMO

BACKGROUND: Urinary incontinence (UI) is an important side effect of radical prostatectomy (RP). Coactivation of surrounding muscles via novel techniques for pelvic floor rehabilitation known as Pfilates and Hypopressives has not been compared to pelvic floor muscle exercises (PFMXs) for UI. OBJECTIVE: To assess the feasibility and efficacy of isolated PFMXs with and without the addition of Pfilates and Hypopressives on UI recovery following RP. DESIGN: Randomized controlled trial. SETTING: Participants were recruited from a community and tertiary cancer center in Toronto, Canada. PARTICIPANTS: A total of 226 patients undergoing RP were assessed for eligibility. One hundred twenty-two patients were eligible and 50 consented to participate; 37 participants completed the trial. METHODS: Participants were randomized to either isolated PFMX (control) or PFMX plus Pfilates and Hypopressives (advanced pelvic floor exercises; APFX) groups. PFMX participants (n = 25) received instructions for isolated pelvic floor contractions starting with 30 contractions per day during weeks 1 to 2 up to 180 per day for weeks 7 to 26. The APFX group (n = 25) received a comparable volume of exercises. MAIN OUTCOME MEASUREMENTS: Feasibility was assessed by rates of recruitment, adverse events, and study-arm compliance. Information about UI and quality of life was collected 1 week before surgery and at 2, 6, 12, and 26 weeks after surgery. RESULTS: The recruitment rate was 41%, adherence to the PFMXs and APFXs was >70%, and there were no reported adverse events. Between-group differences were observed in the frequency of self-reported 24-hour urinary leakage (rate ratio 0.45, 95% confidence interval [CI] 0.2-0.98) and during waking hours (rate ratio 0.43, 95% CI 0.20-0.91) at 26 weeks after surgery favoring APFX. CONCLUSIONS: Pfilates and Hypopressives are feasible in men undergoing RP, and preliminary data suggest a potential benefit in aiding recovery of urinary control. Larger studies with longer follow-up are warranted. LEVEL OF EVIDENCE: II.

10.
Health Informatics J ; 26(3): 1560-1576, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31709878

RESUMO

Mental illnesses are on the rise on campuses worldwide. There is a need for a scalable and economically sound innovation to address these mental health challenges. The aim of this study was to explore university students' needs and concerns in relation to an online mental health virtual community. Eight focus groups (N = 72, 55.6% female) were conducted with university students aged 18-47 (mean = 23.38, SD = 5.82) years. Participants were asked about their views in relation to online mental health platform. Three major themes and subthemes emerged: (1) perceived concerns: potential loss of personal encounter and relationships, fear of cyber bullying, engagement challenge, and privacy and distraction; (2) perceived advantages: anonymity and privacy, convenience and flexibility, filling a gap, and togetherness; and (3) desired features: user-centered design, practical trustworthy support, and online moderation. The analysis informed design features for a mindfulness virtual community.

11.
JMIR Med Inform ; 7(4): e15601, 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31746764

RESUMO

BACKGROUND: Pain volatility is an important factor in chronic pain experience and adaptation. Previously, we employed machine-learning methods to define and predict pain volatility levels from users of the Manage My Pain app. Reducing the number of features is important to help increase interpretability of such prediction models. Prediction results also need to be consolidated from multiple random subsamples to address the class imbalance issue. OBJECTIVE: This study aimed to: (1) increase the interpretability of previously developed pain volatility models by identifying the most important features that distinguish high from low volatility users; and (2) consolidate prediction results from models derived from multiple random subsamples while addressing the class imbalance issue. METHODS: A total of 132 features were extracted from the first month of app use to develop machine learning-based models for predicting pain volatility at the sixth month of app use. Three feature selection methods were applied to identify features that were significantly better predictors than other members of the large features set used for developing the prediction models: (1) Gini impurity criterion; (2) information gain criterion; and (3) Boruta. We then combined the three groups of important features determined by these algorithms to produce the final list of important features. Three machine learning methods were then employed to conduct prediction experiments using the selected important features: (1) logistic regression with ridge estimators; (2) logistic regression with least absolute shrinkage and selection operator; and (3) random forests. Multiple random under-sampling of the majority class was conducted to address class imbalance in the dataset. Subsequently, a majority voting approach was employed to consolidate prediction results from these multiple subsamples. The total number of users included in this study was 879, with a total number of 391,255 pain records. RESULTS: A threshold of 1.6 was established using clustering methods to differentiate between 2 classes: low volatility (n=694) and high volatility (n=185). The overall prediction accuracy is approximately 70% for both random forests and logistic regression models when using 132 features. Overall, 9 important features were identified using 3 feature selection methods. Of these 9 features, 2 are from the app use category and the other 7 are related to pain statistics. After consolidating models that were developed using random subsamples by majority voting, logistic regression models performed equally well using 132 or 9 features. Random forests performed better than logistic regression methods in predicting the high volatility class. The consolidated accuracy of random forests does not drop significantly (601/879; 68.4% vs 618/879; 70.3%) when only 9 important features are included in the prediction model. CONCLUSIONS: We employed feature selection methods to identify important features in predicting future pain volatility. To address class imbalance, we consolidated models that were developed using multiple random subsamples by majority voting. Reducing the number of features did not result in a significant decrease in the consolidated prediction accuracy.

13.
JMIR Res Protoc ; 8(7): e11591, 2019 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-31359869

RESUMO

BACKGROUND: About 70% of all mental health disorders appear before the age of 25 years. When untreated, these disorders can become long-standing and impair multiple life domains. When compared with all Canadian youth (of different ages), individuals aged between 15 and 25 years are significantly more likely to experience mental health disorders, substance dependencies, and risks for suicidal ideation and death by suicide. Progress in the treatment of youth, capitalizing on their online responsivity, can strategically address depressive disorders. OBJECTIVE: We will conduct a randomized controlled trial to compare online mindfulness-oriented cognitive behavioral therapy (CBT-M) combined with standard psychiatric care versus psychiatric care alone in youth diagnosed with major depressive disorder. We will enroll 168 subjects in the age range of 18 to 30 years; 50% of subjects will be from First Nations (FN) backgrounds, whereas the other 50% will be from all other ethnic backgrounds. There will be equal stratification into 2 intervention groups (INT1 and INT2) and 2 wait-list control groups (CTL1 and CTL2) with 42 subjects per group, resulting in an equal number of INT1 and CTL1 of FN background and INT2 and CTL2 of non-FN background. METHODS: The inclusion criteria are: (1) age 18 to 30 years, FN background or other ethnicity; (2) Beck Depression Inventory (BDI)-II of at least mild severity (BDI-II score ≥14) and no upper limit; (3) Mini-International Neuropsychiatric Interview (MINI)-confirmed psychiatric diagnosis of major depressive disorder; and (4) fluent in English. All patients are diagnosed by a Centre for Addiction and Mental Health psychiatrist, with diagnoses confirmed using the MINI interview. The exclusion criteria are: (1) individuals receiving weekly structured psychotherapy; (2) individuals who meet the Diagnostic and Statistical Manual of Mental Disorders criteria for severe alcohol/substance use disorder in the past 3 months, or who demonstrate clinically significant suicidal ideation defined as imminent intent, or who have attempted suicide in the past 6 months; and (3) individuals with comorbid diagnoses of borderline personality, schizophrenia, bipolar disorder, and/or obsessive compulsive disorder. All subjects are provided standard psychiatric care defined as 1 monthly session that focuses on appropriate medication, with session durations of 15 to 30 min. Experimental subjects receive an additional intervention consisting of the CBT-M online software program (in collaboration with Nex J Health, Inc). Exposure to and interaction with the online workbooks are combined with navigation-coaching delivered by phone and secure text message interactions. RESULTS: The outcomes selected, combined with measurement blinding, are key features in assessing whether significant benefits regarding depression and anxiety symptoms occur. CONCLUSIONS: If results confirm the hypothesis that youth can be effectively treated with online CBT-M, effective services may be widely delivered with less geographic restriction. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/11591.

14.
Cancer ; 125(19): 3437-3447, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31206630

RESUMO

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.


Assuntos
Terapia por Exercício/métodos , Implementação de Plano de Saúde/estatística & dados numéricos , Cinesiologia Aplicada/organização & administração , Oncologia/organização & administração , Neoplasias/reabilitação , Adulto , Idoso , Terapia por Exercício/estatística & dados numéricos , Feminino , Serviços Hospitalares de Assistência Domiciliar/organização & administração , Serviços Hospitalares de Assistência Domiciliar/estatística & dados numéricos , Humanos , Cinesiologia Aplicada/métodos , Cinesiologia Aplicada/estatística & dados numéricos , Masculino , Oncologia/métodos , Oncologia/estatística & dados numéricos , Pessoa de Meia-Idade , Neoplasias/psicologia , Equipe de Assistência ao Paciente/organização & administração , Pacientes Desistentes do Tratamento/estatística & dados numéricos , Satisfação do Paciente , Avaliação de Programas e Projetos de Saúde , Qualidade de Vida , Encaminhamento e Consulta/organização & administração , Encaminhamento e Consulta/estatística & dados numéricos , Resultado do Tratamento
15.
Int J Ment Health Syst ; 13: 17, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30962817

RESUMO

Background: Young adults starting college or university education encounter multiple stressors related to transitional life-stage and novel environments. Current studies reveal high rates of symptoms related to common mental health problems like depression, anxiety and stress. However, limited knowledge exists on the determinants on these problems among Canadian students. The primary aim of the study was to investigate the impact of contextual determinants, as perceived by students, on self-reported mental health, and how these impacts varied by depression, anxiety and stress. Methods: A cross-sectional survey was conducted with students attending a large university in Toronto, Canada. Participants completed a self-administered online questionnaire as part of a larger project. The questions asked about contextual determinants related to personal, interpersonal, family, social, socio-economic and political factors along with levels of depression, anxiety and stress as measured by Patient Health Questionnaire-9, Beck Anxiety Inventory and Perceived Stress Scale. Results: A total of 148 students completed the questionnaire (37 males and 111 females) with an age range of 19-54 years (median 22, IQR 21-24.8). English was reported as first language by 62.8% while 34.5% self-identified as white and 58.1% reported being born in Canada. Overall, 39.5% reported symptoms of moderate to severe depression, 23.8% reported moderate-severe anxiety and 80.3% reported moderate-severe levels of perceived stress, with no significant differences between males and females. In the final multivariate analysis, variables significantly associated with depression were grade-point-average (aOR 2.46, 95% CI 1.017-5.97), family factors (aOR 3.46, 95% CI 1.50-7.94), social factors (aOR 3.24, 1.30-8.1), self-rated health (aOR 0.34, 95% CI 0.14-0.82) and political factors (aOR 0.40, 95% CI 0.16-0.97). Anxiety was significantly associated with family factors (aOR 2.79, 1.09-7.18), socioeconomic factors (aOR 2.59, 95% CI 1.05-6.42) and age (aOR 0.33, 95% CI 0.11-0.98). The significant factors for stress were grade-point-average (aOR 2.41, 1.01-5.75) and social factors (aOR 3.87, 95% CI 1.59-9.43). Conclusion: The study found strong to moderate impact of several determinants on depression, anxiety and stress. The results suggest a need to address a variety of factors affecting students' mental health.Trial registration Parent trial: http://www.isrctn.com/ISRCTN92827275.

16.
Front Immunol ; 10: 250, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30873158

RESUMO

The role of interleukin-1 in the regulation of humoral responses is poorly documented, in contrast to its role in inflammation. Recent findings suggest there is an interleukin-1 axis in the follicular T cell control of B cell responses, involving interleukin-1 receptors (IL-1R1 and IL-1R2) and receptor antagonists (IL-1Ra). Here, we revisit the literature on this topic and conclude that targeting the interleukin-1 pathway should be a valuable therapeutic approach in many diseases involving excessive production of (auto)antibodies, such as autoimmune diseases or allergy.


Assuntos
Interleucina-1/fisiologia , Linfócitos T Auxiliares-Indutores/imunologia , Linfócitos T Reguladores/imunologia , Doenças Autoimunes/imunologia , Humanos , Hipersensibilidade/imunologia , Imunidade Humoral , Proteína Antagonista do Receptor de Interleucina 1/uso terapêutico , Transdução de Sinais
17.
BMC Cancer ; 19(1): 2, 2019 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-30606137

RESUMO

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.


Assuntos
Terapia por Exercício , Força Muscular/fisiologia , Aptidão Física , Neoplasias da Próstata/terapia , Idoso , Antagonistas de Androgênios/administração & dosagem , Antineoplásicos Hormonais/administração & dosagem , Canadá/epidemiologia , Exercício Físico , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/fisiopatologia , Qualidade de Vida , Autorrelato
18.
Am J Health Promot ; 33(5): 778-791, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30586996

RESUMO

OBJECTIVE: To evaluate the effectiveness of wearable device interventions (eg, Fitbit) to improve physical activity (PA) outcomes (eg, steps/day, moderate to vigorous physical activity [MVPA]) in populations diagnosed with cardiometabolic chronic disease. DATA SOURCE: Based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses, an electronic search of 5 databases (Medline, PsychINFO, Scopus, Web of Science, and PubMed) was conducted. STUDY INCLUSION AND EXCLUSION CRITERIA: Randomized controlled trials (RCTs) published between January 2000 and May 2018 that used a wearable device for the full intervention in adults (18+) diagnosed with a cardiometabolic chronic disease were included. Excluded trials included studies that used devices at pre-post only, devices that administered medication, and interventions with no prospective control group comparison. DATA EXTRACTION: Thirty-five studies examining 4528 participants met the inclusion criteria. Study quality and RCT risk of bias were assessed using the Cochrane Collaboration Tool. DATA SYNTHESIS: Meta-analyses to compute PA (eg, steps/day) and selected physical dispersion and summary effects were conducted using the raw unstandardized pooled mean difference (MD). Sensitivity analyses were examined. RESULTS: Statistically significant increases in PA steps/day (MD = 2592 steps/day; 95% confidence interval [CI]: 1689-3496) and MVPA min/wk (MD = 36.31 min/wk; 95% CI: 18.33-54.29) were found for the intervention condition. CONCLUSION: Wearable devices positively impact physical health in clinical populations with cardiometabolic diseases. Future research using the most current technologies (eg, Fitbit) will serve to amplify these findings.


Assuntos
Doenças Cardiovasculares/epidemiologia , Exercício Físico/fisiologia , Dispositivos Eletrônicos Vestíveis , Doença Crônica , Comorbidade , Humanos , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto
19.
J Med Internet Res ; 20(11): e12001, 2018 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-30442636

RESUMO

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.


Assuntos
Dor Crônica/diagnóstico , Mineração de Dados/métodos , Aprendizado de Máquina/tendências , Aplicativos Móveis/tendências , Volatilização , Gerenciamento Clínico , Humanos
20.
BMC Cancer ; 18(1): 1031, 2018 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-30352568

RESUMO

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.


Assuntos
Terapia por Exercício , Neoplasias da Próstata/terapia , Antagonistas de Androgênios/uso terapêutico , Ensaios Clínicos Fase III como Assunto , Análise Custo-Benefício , Terapia por Exercício/economia , Terapia por Exercício/métodos , Humanos , Masculino , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/economia , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
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