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Background Effective strategies for participant retention are critical in health research to ensure validity, generalizability and efficient use of resources. Yet standardized guidelines for planning and reporting on retention efforts have been lacking. As with randomized controlled trial (RCT) and systematic review (SR) protocols, retention protocols are an opportunity to improve transparency and rigor. An RCT being conducted in British Columbia (BC), Canada provides a case example for developing a priori retention frameworks for use in protocol planning and reporting. Methods The BC Healthy Connections Project RCT is examining the effectiveness of a nurse home-visiting program in improving child and maternal outcomes compared with existing services. Participants ( N  = 739) were girls and young women preparing to parent for the first time and experiencing socioeconomic disadvantage. Quantitative data were collected upon trial entry during pregnancy and during five follow-up interviews until participants’ children reached age 2 years. A framework was developed to guide retention of this study population throughout the RCT. We reviewed relevant literature and mapped essential retention activities across the study planning, recruitment and maintenance phases. Interview completion rates were tracked. Results Results from 3302 follow-up interviews (in-person/telephone) conducted over 4 years indicate high completion rates: 90% ( n  = 667) at 34 weeks gestation; and 91% ( n  = 676), 85% ( n  = 626), 80% ( n  = 594) and 83% ( n  = 613) at 2, 10, 18 and 24 months postpartum, respectively. Almost all participants (99%, n  = 732) provided ongoing consent to access administrative health data. These results provide preliminary data on the success of the framework. Conclusions Our retention results are encouraging given that participants were experiencing considerable socioeconomic disadvantage. Standardized retention planning and reporting may therefore be feasible for health research in general, using the framework we have developed. Use of standardized retention protocols should be encouraged in research to promote consistency across diverse studies, as now happens with RCT and SR protocols. Beyond this, successful retention approaches may help inform health policy-makers and practitioners who also need to better reach, engage and retain underserved populations. Trial registration ClinicalTrials.gov , NCT01672060 . Registered on 24 August 2012.

Background Indigenous Peoples comprise the youngest and fastest growing demographic in Canada, with many living in urban-suburban areas. Given higher fertility rates, younger overall ages and higher adolescent pregnancy rates, perinatal research is needed—to inform policymaking and programming throughout pregnancy and childhood. Yet such data remain scarce in British Columbia (BC), Canada. This study therefore aimed to describe the experiences of young, urban, Indigenous mothers-to-be who enrolled in a larger BC early prevention trial designed to reach families experiencing socioeconomic disadvantage. Methods This descriptive study utilized baseline data from a trial that enrolled first-time mothers-to-be who met indicators of socioeconomic disadvantage and who were residing in select urban-suburban areas. These indicators included being young (19 years or younger) or having limited income, low access to education, and being single (aged 20−24 years). We described and compared survey data on girls ( n  = 109; aged 14−19 years) and young women ( n  = 91; aged 20−24 years) using Chi-square or Student’s t -tests. Results Of the 739 trial participants, 200 or 27% identified as Indigenous and met trial eligibility criteria: limited income (92.9%), limited access to education (67.0%), and/or being single (90.9%). Beyond this, participants reported associated adversities including: unstable housing (63.3%), psychological distress (29.3%), severe anxiety or depression (48.5%), experiences of childhood maltreatment (59.4%) and intimate partner violence (39.5%). Compared to girls, young women reported higher income and educational attainment ( p  < 0.001), more unstable housing ( p  = 0.02) and more childhood maltreatment ( p  = 0.014). Many had recently received primary healthcare (75%), but few had received income assistance (34%). Most (80.5%) reported experiencing four or more adversities. Conclusions We present data illustrating that a high proportion of pregnant Indigenous girls and young women engaged with public health and consented to long-term research participation—despite experiencing cumulative adversities. The trial socioeconomic screening criteria were successful in reaching this population. Girls and young women reported relatively similar experiences—beyond expected developmental differences in income and education—suggesting that adolescent maternal age may not necessarily infer risk. Our findings underscore the need for Indigenous community-led services that address avoidable adversities starting in early pregnancy.

Youth exposed to early-life adversity (ELA) are at greater risk for poorer physical and mental health outcomes in adolescence and adulthood. Although the biological mechanisms underlying these associations remain elusive, DNA methylation (DNAm) has emerged as a potential pathway. DNAm-based measures of epigenetic age have been associated with ELA, indicating accelerated aging. According to the stress sensitization hypothesis, prenatal adversity may further heighten sensitivity to subsequent stressors in childhood and adolescence. This study examined the associations between ELA and six epigenetic aging measures, considering both the timing of adversity and the participant’s sex. Data were drawn from the Quebec Longitudinal Study of Child Development, with two cumulative indices of ELA derived from prospectively collected data: the Perinatal Adversity and the Child and Adolescent Adversity indices. Higher Perinatal Adversity scores were associated with accelerated DunedinPACE scores. No significant associations were found between ELA and the other epigenetic clocks, nor did we find support for the stress sensitization hypothesis—though a sex-specific trend emerged among girls. The findings suggest that DunedinPACE may be more sensitive to variations in ELA than other clocks. Future research should systematically investigate sex-dimorphic associations between ELA and epigenetic aging, with particular attention to the impact of perinatal adversity.

IntroductionThe introduction of fentanyl and its analogues in the illicit drug supply has prompted greater emphasis on refining clinical treatment protocols to ensure sustained retention in opioid agonist treatment (OAT). Take-home dosing may lessen the treatment burden on clients and thus reduce the risk of treatment discontinuation. The evidence base supporting the use of take-home dosing, including the optimal duration of dispensations, is, however, limited. The objective of this study is to determine the comparative effectiveness of alternative take-home dosing schedules, as observed in clinical practice in British Columbia, Canada from 2010 to 2022.Methods and analysisWe propose to emulate a target trial with a population-level retrospective study of individuals initiating methadone or buprenorphine/naloxone between 1 January 2010 and 31 December 2022 who are 18 years of age or older and not currently incarcerated or pregnant with no history of cancer or palliative care. Our study will draw on nine linked health administrative databases from British Columbia and will evaluate take-home doses of 2–5 days, 6 days or >6 days compared with continuous daily dosing. The primary outcomes include OAT discontinuation and all-cause mortality on treatment. A causal per-protocol analysis is proposed with longitudinal matching and inverse probability of censoring weighting approaches to adjust for time-fixed and time-varying confounding. A range of sensitivity analyses will be executed to determine the robustness of results.Ethics and disseminationThe protocol, cohort creation and analysis plan have been classified and approved as a quality improvement initiative by Providence Health Care Research Ethics Board and the Simon Fraser University Office of Research Ethics. Results will be disseminated and shared with local advocacy groups and decision-makers, developers of national and international clinical guidelines, presented at national and international conferences and published in peer-reviewed journals electronically and in print.

Background Maternal exposure to socioeconomic disadvantage increases the risk of child injuries and subsequent child developmental and mental health problems — particularly for young mothers. To inform early intervention planning, this research therefore aimed to describe the health and social adversities experienced by a cohort of girls and young women in early pregnancy in British Columbia (BC), Canada. Methods Participants were recruited for the BC Healthy Connections Project (BCHCP), a randomized controlled trial examining the effectiveness of Nurse-Family Partnership, a home visitation program, in improving child and maternal outcomes. Baseline data were collected from 739 participants on trial entry. Participants were selected on the basis of preparing to parent for the first time and experiencing socioeconomic disadvantage. Analyses involved descriptive statistics and age-group comparisons. Results Most participants reported having low income (84%), having limited education (52%) and being single (91%) at trial entry. Beyond these eligibility criteria, other health and social adversities included: housing instability (52%); severe anxiety or depression (47%); other diagnosed mental disorders (22%); prenatal nicotine and cannabis use (27 and 21%); physical health problems (20%); child maltreatment when younger (56%); and intimate partner violence recently (50%). As well, few (29%) had received income assistance entitlements. More than two thirds (70%) were experiencing four or more forms of adversity. Age-group differences were observed for cognitive functioning, being single, low income, limited education, psychological distress and service use ( p -value ≤0.05). Conclusions This cohort was selected on the basis of socioeconomic disadvantage. Yet all participants were experiencing substantial added adversities — at higher rates than other Canadians. Furthermore, despite Canada’s public programs, these pregnant girls and young women were not being adequately reached by social services. Our study adds new data to inform early intervention planning, suggesting that unacceptably high levels of socioeconomic disadvantage exist for some young British Columbians. Therefore greater health and social supports and services are warranted for these young mothers and their children. Trial registration Registered August 24, 2012 with ClinicalTrials.gov Identifier: NCT01672060 . Active not recruiting.

ObjectiveTo evaluate the impact of Nurse-Family Partnership (NFP), a home-visiting programme, on exploratory maternal outcomes in British Columbia (BC), Canada.DesignPragmatic, parallel arm, randomised controlled trial conducted October 2013–November 2019. Random allocation of participants (1:1) to comparison (existing services) or NFP (plus existing services). Researchers were naïve to allocation.Setting26 local health areas across four of five BC regional health authorities.Participants739 young (<25 years), first-time mothers (enrolled <28 weeks gestation), experiencing socioeconomic disadvantage.InterventionPublic health nurses with NFP education offered home visits (up to 64) during pregnancy and until children’s second birthday plus existing services on offer in BC.Outcome measuresPrespecified exploratory outcomes included exposure to intimate partner violence (IPV), income (annual from employment) and not in education, employment or training (NEET) by 24 months postpartum, and psychological distress and self-efficacy across five time points (34–36 weeks gestation, 2, 10, 18 and 24 months postpartum).ResultsA total of 739 participants were randomised (368 NFP, 371 comparison) and analysed via an intention-to-treat analysis. At 24 months postpartum, for participants receiving NFP, a lower percentage reported IPV (group difference −7.14; 95% CI: –14.17, –0.10); incomes were larger ($1629.74, 95% CI: $5.20, $3254.28) after adjusting for baseline differences and no difference in percentage of NEET (−2.41, 95% CI: −10.11, 5.30). For participants receiving NFP, psychological distress was lower across time points (−1.59, 95% CI: −2.35 to –0.84); self-efficacy was greater at 34–36 weeks gestation (0.78, 95% CI: 0.34, 1.22), then decreasing and becoming insignificant by 24 months postpartum (0.29, 95% CI: −0.18, 0.75). No unanticipated serious adverse events were reported.ConclusionRelying on the maternal report, at 24 months postpartum, the NFP group had reduced IPV exposure and increased incomes. Benefits observed in late pregnancy were sustained to study end for psychological distress, but not self-efficacy. Longer-term follow-up is recommended.Trial registration NCT01672060.

Background Nurse-Family Partnership is a nurse home visitation program that aims to improve the lives of young mothers and their children. The program focuses on women who are parenting for the first time and experiencing socioeconomic disadvantage. Nurse visits start as early in pregnancy as possible and continue until the child reaches age two years. The program has proven effective in the United States – improving children’s mental health and development and maternal wellbeing, and showing long-term cost-effectiveness. But it is not known whether the same benefits will be obtained in Canada, where public services differ. The British Columbia Healthy Connections Project therefore involves a randomized controlled trial evaluating Nurse-Family Partnership’s effectiveness compared with existing (usual) services in improving children’s mental health and early development and mother’s life circumstances. The trial’s main aims are to: reduce childhood injuries by age two years (primary outcome indicator); reduce prenatal nicotine and alcohol use; improve child cognitive and language development and behaviour at age two years; and reduce subsequent pregnancies by 24 months postpartum. Potential explanatory factors such as maternal mental health (including self-efficacy) are also being assessed, as is the program’s impact on exposure to intimate-partner violence. To inform future economic evaluation, data are also being collected on health and social service access and use. Methods/design Eligible and consenting participants ( N  = 1040) are being recruited prior to 28 weeks gestation then individually randomized to receive existing services (comparison group) or Nurse-Family Partnership plus existing services (intervention group). Nurse-Family Partnership is being delivered following fidelity guidelines. Data are being collected during in person and telephone interviews at: baseline; 34–36 weeks gestation; and two, 10, 18 and 24 months postpartum. Additional data will be obtained via linkages from provincial datasets. Recruitment commenced in October 2013 and will continue for approximately three years. Discussion This trial will provide important information about the generalizability of Nurse-Family Partnership to the Canadian context. Findings will be published in peer-reviewed journals and shared with policymakers and practitioners through extensive public health collaborations already underway. Trial registration Registered July 18, 2013 with ClinicalTrials.gov Identifier: NCT01672060 .

Until recently, research on serious conduct problems focused primarily on boys and men. In the past decade, however, we have gained a better understanding of the unique and shared risk and protective factors for girls and boys, and the role of gender in relation to developmental pathways associated with such problems. In this paper we discuss findings from the Gender and Aggression Project on risk and protective factors for girls who are perpetrators but also victims of violence. We discuss our findings from a developmental perspective, with the goal of understanding how exposure to adversity and violence early in life places girls at risk for aggression and violence, among other problems, and how continued exposure to trauma and the disruption of interpersonal and self-regulatory developmental processes cascades into ever deeper and broader problems. This research points more clearly to the need for  accessible, evidence-based, and developmentally sensitive intervention.

Multiple organizations around the world have issued evidence‐based exercise guidance for patients with cancer and cancer survivors. Recently, the American College of Sports Medicine has updated its exercise guidance for cancer prevention as well as for the prevention and treatment of a variety of cancer health‐related outcomes (eg, fatigue, anxiety, depression, function, and quality of life). Despite these guidelines, the majority of people living with and beyond cancer are not regularly physically active. Among the reasons for this is a lack of clarity on the part of those who work in oncology clinical settings of their role in assessing, advising, and referring patients to exercise. The authors propose using the American College of Sports Medicine's Exercise Is Medicine initiative to address this practice gap. The simple proposal is for clinicians to assess, advise, and refer patients to either home‐based or community‐based exercise or for further evaluation and intervention in outpatient rehabilitation. To do this will require care coordination with appropriate professionals as well as change in the behaviors of clinicians, patients, and those who deliver the rehabilitation and exercise programming. Behavior change is one of many challenges to enacting the proposed practice changes. Other implementation challenges include capacity for triage and referral, the need for a program registry, costs and compensation, and workforce development. In conclusion, there is a call to action for key stakeholders to create the infrastructure and cultural adaptations needed so that all people living with and beyond cancer can be as active as is possible for them.

Histone deacetylase (HDAC) inhibitors are an important new class of therapeutics for treating multiple myeloma. Ricolinostat (ACY-1215) is the first oral selective HDAC6 inhibitor with reduced class I HDAC activity to be studied clinically. Motivated by findings from preclinical studies showing potent synergistic activity with ricolinostat and lenalidomide, our goal was to assess the safety and preliminary activity of the combination of ricolinostat with lenalidomide and dexamethasone in relapsed or refractory multiple myeloma. In this multicentre phase 1b trial, we recruited patients aged 18 years or older with previously treated relapsed or refractory multiple myeloma from five cancer centres in the USA. Inclusion criteria included a Karnofsky Performance Status score of at least 70, measureable disease, adequate bone marrow reserve, adequate hepatic function, and a creatinine clearance of at least 50 mL per min. Exclusion criteria included previous exposure to HDAC inhibitors; previous allogeneic stem-cell transplantation; previous autologous stem-cell transplantation within 12 weeks of baseline; active systemic infection; malignancy within the last 5 years; known or suspected HIV, hepatitis B, or hepatitis C infection; a QTc Fridericia of more than 480 ms; and substantial cardiovascular, gastrointestinal, psychiatric, or other medical disorders. We gave escalating doses (from 40–240 mg once daily to 160 mg twice daily) of oral ricolinostat according to a standard 3 + 3 design according to three different regimens on days 1–21 with a conventional 28 day schedule of oral lenalidomide (from 15 mg [in one cohort] to 25 mg [in all other cohorts] once daily) and oral dexamethasone (40 mg weekly). Primary outcomes were dose-limiting toxicities, the maximum tolerated dose of ricolinostat in this combination, and the dose and schedule of ricolinostat recommended for further phase 2 investigation. Secondary outcomes were the pharmacokinetics and pharmacodynamics of ricolinostat in this combination and the preliminary anti-tumour activity of this treatment. The trial is closed to accrual and is registered at ClinicalTrials.gov, number NCT01583283. Between July 12, 2012, and Aug 20, 2015, we enrolled 38 patients. We observed two dose-limiting toxicities with ricolinostat 160 mg twice daily: one (2%) grade 3 syncope and one (2%) grade 3 myalgia event in different cohorts. A maximum tolerated dose was not reached. We chose ricolinostat 160 mg once daily on days 1–21 of a 28 day cycle as the recommended dose for future phase 2 studies in combination with lenalidomide 25 mg and dexamethasone 40 mg. The most common adverse events were fatigue (grade 1–2 in 14 [37%] patients; grade 3 in seven [18%]) and diarrhoea (grade 1–2 in 15 [39%] patients; grade 3 in two [5%]). Our pharmacodynamic studies showed that at clinically relevant doses, ricolinostat selectively inhibits HDAC6 while retaining a low and tolerable level of class I HDAC inhibition. The pharmacokinetics of ricolinostat and lenalidomide were not affected by co-administration. In a preliminary assessment of antitumour activity, 21 (55% [95% CI 38–71]) of 38 patients had an overall response. The findings from this study provide preliminary evidence that ricolinostat is a safe and well tolerated selective HDAC6 inhibitor, which might partner well with lenalidomide and dexamethasone to enhance their efficacy in relapsed or refractory multiple myeloma. Acetylon Pharmaceuticals.