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Maya Kshatriya,1– 3 Kuan-Wen Wang,1,2 Julia Hildebrand,1,2 Rebecca Crawford,1,2,4 Ajantha Nadarajah,1– 3 Michael Youssef,1,2 Angelica Rivas,1,2,5 Ashleen Kaushal,1,2 Laura E Banfield,6 Lehana Thabane,7– 10 M Constantine Samaan1– 3,5,7 1Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada; 2Division of Pediatric Endocrinology, McMaster Children’s Hospital, Hamilton, Ontario, Canada; 3Global Health Graduate Program, McMaster University, Hamilton, Ontario, Canada; 4Indigenous Undergraduate Summer Research Program, McMaster University, Hamilton, Ontario, Canada; 5Michael G. De Groote School of Medicine, McMaster University, Hamilton, Ontario, Canada; 6Health Sciences Library, McMaster University, Hamilton, Ontario, Canada; 7Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Ontario, Canada; 8Biostatistics Unit, St. Joseph’s Healthcare-Hamilton, Hamilton, Ontario, Canada; 9Department of Anesthesia, McMaster University, Hamilton, Ontario, Canada; 10Centre for Evaluation of Medicines, St. Joseph’s Health Care, Hamilton, Ontario, CanadaCorrespondence: M Constantine Samaan, Department of Pediatrics, McMaster University, 1280 Main Street West, HSC-3A57, Hamilton, Ontario, L8S 4K1, Canada, Tel +1-905-521-2100, ext. 75926, Fax +1-905-308-7548, Email samaanc@mcmaster.caBackground: Indigenous children in Canada have high rates of obesity and type 2 diabetes mellitus (T2DM). Culturally appropriate interventions, guided by an Indigenous knowledge-based view of health, are crucial to target these conditions. The objective of this systematic review was to assess the impact of indigenous Knowledge-based lifestyle interventions on the prevention of obesity and T2DM in Indigenous children in Canada.Methods: Database searches were conducted from inception until February 22, 2022. The main outcomes were changes in Body Mass Index (BMI) z-score and the development of T2DM. The other outcomes included adiposity, metabolic, and lifestyle determinants of health. The GRADE approach was used to assess confidence in the evidence.Results: Four non-randomized controlled trials (non-RCTs) and six uncontrolled studies were identified. Peer-led interventions led to a reduction in BMI z-score and waist circumference. GRADE assessment revealed very low quality of evidence due to a lack of randomization and small sample sizes. There were no diabetes-specific reported programs.Conclusion: Limited evidence from non-randomized studies suggest that peer-led indigenous Knowledge-based lifestyle interventions improve BMI z-score and central adiposity. There is a need for community-owned and adequately powered randomized studies for interventions that aim to treat and prevent obesity and T2DM in Indigenous children in Canada.Systematic Review Registration: PROSPERO CRD42017072781.Keywords: child, ethnicity, obesity, diabetes, prevention

Nitika Sanger,1,* Balpreet Panesar,2,* Michael Dennis,3 Tea Rosic,4 Myanca Rodrigues,4 Elizabeth Lovell,5 Shuling Yang,3 Mehreen Butt,6 Lehana Thabane,4,7 Zainab Samaan4,5 1Medical Science Graduate Program, McMaster University, Hamilton, Ontario, Canada; 2Neuroscience Graduate Program, McMaster University, Hamilton, Ontario, Canada; 3Michael G DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada; 4Health Research Methodology Graduate Program, McMaster University, Hamilton, Ontario, Canada; 5Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, Ontario, Canada; 6Accelerated Nursing Program, McMaster University, Hamilton, Ontario, Canada; 7Centre for Evaluation of Medicines, Programs for Assessment of Technology in Health (PATH) Research Institute, McMaster University, Hamilton, Ontario, Canada*These authors contributed equally to this workCorrespondence: Zainab Samaan, Health Research Methodology Graduate Program, McMaster University, Department of Psychiatry and Behavioural Neurosciences, McMaster University, 1280 Main St. West, Hamilton, Ontario, Canada, Tel +1 905-522-1155 ext. 35448, Fax +1 905-381-5629, Email samaanz@mcmaster.caIntroduction: Patient centred care is needed now more than ever in the treatment of opioid use disorder. Trials, policy makers, and service providers have most often used treatment retention and opioid urine screens as measures of treatment effectiveness. However, patients receiving medication for opioid use disorder treatment (MOUD) may prioritise the use of different ways to assess treatment success.Objective: The aim of this review is to synthesize literature examining the self-reported goals patients would like to achieve in MOUD for opioid use disorder.Methods: We searched MEDLINE, EMBASE, PsycINFO, Cumulative Index to Nursing and Allied Health Literature, Web of Science, Cochrane Library, Cochrane Clinical Trials Registry, the National Institutes for Health Clinical Trials Registry, and the WHO International Clinical Trials Registry Platform from inception until April 30th, 2021. No restrictions were placed on language, age, or type of MOUD. A qualitative synthesis is presented given that a meta-analysis was not possible.Results: The search yielded a total of 21,082 records from which 8 met criteria for inclusion in the qualitative synthesis. We identified a total of 43 patient-reported treatment goals from the 8 studies. Twelve domains were created from the 43 goals reported. These domains cover a range of important areas for patients’ goals related to living a normal life, physical health, mental health, treatment, and substance use specific areas.Conclusion: This review highlights several patient goals that they would like to achieve during treatment for opioid use disorder that are not commonly considered as markers of treatment effectiveness. Goals related to health, living a normal life, and overall substance use concerns by patients should be taken into consideration by clinical trialists, researchers, policy makers, service providers, patients, and communities engaged in developing and tailoring treatment plans for opioid use disorder.Systematic Review Registration: PROSPERO CRD42018095553.Keywords: opioid use disorder, patient reported outcomes, patient-centred care, medication for opioid use disorder

Brianna Empringham,1,2 William J Jennings,1,2 Raeesha Rajan,1– 3 Adam J Fleming,1,4 Carol Portwine,1,4 Donna L Johnston,5 Shayna M Zelcer,6 Shahrad Rod Rassekh,7 Victoria Tran,1,2 Sarah Burrow,8 Lehana Thabane,3,9– 11 M Constantine Samaan1– 3 1Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada; 2Division of Pediatric Endocrinology, McMaster Children’s Hospital, Hamilton, Ontario, Canada; 3Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Ontario, Canada; 4Division of Pediatric Hematology/Oncology, McMaster Children’s Hospital, Hamilton, Ontario, Canada; 5Division of Pediatric Hematology/Oncology, Children’s Hospital of Eastern Ontario, Ottawa, Ontario, Canada; 6Pediatric Hematology Oncology, Children’s Hospital, London Health Sciences Center, London, Ontario, Canada; 7Division of Pediatric Hematology/Oncology/BMT, Department of Pediatrics, British Columbia’s Children’s Hospital, Vancouver, BC, Canada; 8Division of Orthopedic Surgery, Department of Surgery, McMaster University Medical Centre, Hamilton, Ontario, Canada; 9Department of Anesthesia, McMaster University, Hamilton, Ontario, Canada; 10Centre for Evaluation of Medicines, St. Joseph’s Health Care, Hamilton, Ontario, Canada; 11Biostatistics Unit, St Joseph’s Healthcare-Hamilton, Hamilton, Ontario, CanadaCorrespondence: M Constantine SamaanDepartment of Pediatrics, McMaster University, Division of Pediatric Endocrinology, McMaster Children’s Hospital, 1280 Main Street West, 3A-57, Hamilton, Ontario, L8S 4K1 Tel +001-905-521-2100, ext. 75926Fax +001-905-308-7548Email samaanc@mcmaster.caBackground: Obesity is characterized by the disproportionate expansion of the fat mass and is most commonly diagnosed using the Body Mass Index (BMI) z-score or percentile in children. However, these measures associate poorly with the fat mass. This is important, as adiposity is a more robust predictor of cardiometabolic risk than BMI-based measures, but there are limited clinical measures of adiposity in children. A new measure, the Tri-ponderal Mass Index (TMI, kg/m3) has recently demonstrated robust prediction of adiposity in children. The aim of this study is to explore the association of leptin, a validated biomarker of the fat mass, with TMI.Methods: One hundred and eight children and adolescents were included in this cross-sectional study. Height and weight were used to calculate TMI. Plasma leptin was measured using ELISA. Multivariable regression analysis was applied to determine the predictors of TMI.Results: The age range of participants included in this study was 8.00– 16.90 years (female n=48, 44%). Leptin correlated with BMI percentile (r=0.64, p-value < 0.0001) and TMI (r=0.71, p-value < 0.0001). The multivariable regression analysis revealed that BMI percentile (Estimated Beta-coefficient 0.002, 95% CI 0.002– 0.003, p-value < 0.0001) and Leptin (Estimated Beta-coefficient 0.05, 95% CI 0.02– 0.07, p-value 0.013) were associated with TMI.Conclusion: Leptin is associated with TMI in healthy children. The TMI is a feasible clinical measure of adiposity that may be used to stratify children and adolescents for further assessments and interventions to manage and attempt to prevent cardiometabolic comorbidities.Keywords: Tri-ponderal mass index, adiposity, leptin, children

Joycelyne E Ewusie,1,2 Lehana Thabane,1 Joseph Beyene,1 Sharon E Straus,3 Jemila S Hamid1,2,4 1Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada; 2School of Epidemiology and Public Health, University of Ottawa, Ottawa, Canada; 3Li Ka Shing Knowledge Institute of St Michael’s Hospital, Toronto, Ontario, Canada; 4Children’s Hospital of Eastern Ontario, Ottawa, Ontario, CanadaCorrespondence: Jemila S HamidChildren’s Hospital of Eastern Ontario, Ottawa, Ontario, CanadaTel +1 613 737-7600 x 4194Email jhamid@uottawa.caBackground: Segmented regression (SR) is the most common statistical method used in the analysis of interrupted time series (ITS) data. However, this modeling strategy is indicated to produce spurious results when applied to aggregated data. For multicenter ITS studies, data at a given time point are often aggregated across different participants and settings; thus, conventional segmented regression analysis may not be an optimal approach. Our objective is to provide a robust method for analysis of ITS data, while accounting for two sources of heterogeneity, between participants and across sites.Methods: We present a methodological framework within the segmented regression modeling strategy, where we introduced weights to account for between-participant variation and the differences across multiple sites. We empirically compared the proposed weighted segmented regression (wSR) with the conventional SR as well as with a previously published pooled analysis method using data from the Mobility of Vulnerable Elders in Ontario (MOVE-ON) project, a multisite ITS study.Results: Overall, the wSR produced the most precise estimates, where they had the narrowest 95% CI, while the conventional SR method resulted in the least precise estimates. Our method also resulted in increased power. The pooled analysis method and the wSR had comparable results when there were ≤ 4 sites included in the overall analysis and when there was moderate to high between-site heterogeneity as measured by the I2 statistic.Conclusion: Incorporating participant-level and site-level variability led to estimates that were more precise and accurate in determining the magnitude of the effect of an intervention and led to increased statistical power. This underscores the importance of accounting for the inherent variability in aggregated data. Extensive simulations are required to further assess the methods in a wide range of scenarios and outcome types.Keywords: aggregated data, weighted segmented regression, pooled analysis, interrupted time series, multisite studies

Joycelyne E Ewusie,1 Charlene Soobiah,2,3 Erik Blondal,2,3 Joseph Beyene,1 Lehana Thabane,1,4 Jemila S Hamid1,5 1Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada; 2Li Ka Shing Knowledge Institute of St Michael’s Hospital, Toronto, Ontario, Canada; 3Institute of Health Policy Management and Evaluation (IHPME), University of Toronto, Toronto, ON, Canada; 4Biostatistics Unit, Father Sean O’Sullivan Research Centre, St Joseph’s Healthcare, Hamilton, Ontario, Canada; 5Clinical Research Unit, Children’s Hospital of Eastern Ontario, Ottawa, ON, CanadaCorrespondence: Jemila S HamidChildren’s Hospital of Eastern Ontario, 401 Smyth Road, Ottawa, ON K1H 8L1, CanadaTel +1 (613) 737-7600 x 4194Email jhamid@uottawa.caObjective: Interrupted time series (ITS) designs are robust quasi-experimental designs commonly used to evaluate the impact of interventions and programs implemented in healthcare settings. This scoping review aims to 1) identify and summarize existing methods used in the analysis of ITS studies conducted in health research, 2) elucidate their strengths and limitations, 3) describe their applications in health research and 4) identify any methodological gaps and challenges.Design: Scoping review.Data Sources: Searches were conducted in MEDLINE, JSTOR, PUBMED, EMBASE, CINAHL, Web of Science and the Cochrane Library from inception until September 2017.Study Selection: Studies in health research involving ITS methods or reporting on the application of ITS designs.Data Extraction: Screening of studies was completed independently and in duplicate by two reviewers. One reviewer extracted the data from relevant studies in consultations with a second reviewer. Results of the review were presented with respect to methodological and application areas, and data were summarized using descriptive statistics.Results: A total of 1389 articles were included, of which 98.27% (N=1365) were application papers. Segmented linear regression was the most commonly used method (26%, N=360). A small percentage (1.73%, N=24) were methods papers, of which 11 described either the development of novel methods or improvement of existing methods, 7 adapted methods from other areas of statistics, while 6 provided comparative assessment of conventional ITS methods.Conclusion: A significantly increasing trend in ITS use over time is observed, where its application in health research almost tripled within the last decade. Several statistical methods are available for analyzing ITS data. Researchers should consider the types of data and validate the required assumptions for the various methods. There is a significant methodological gap in ITS analysis involving aggregated data, where analyses involving such data did not account for heterogeneity across patients and hospital settings.Keywords: interrupted time series, segmented linear regression, ARIMA, limitations, methods, scoping review

Harsha Shanthanna,1 Alparslan Turan,2 Jessica Vincent,3 Remie Saab,2 Yaron Shargall,4 Turlough O’Hare,1 Kimberly Davis,5 Sylvanus Fonguh,3 Kumar Balasubramaniam,3 James Paul,1 Ian Gilron,6 Henrik Kehlet,7 Daniel I Sessler,2 Mohit Bhandari,8 Lehana Thabane,9 PJ Devereaux9 1Department of Anesthesia, McMaster University, Hamilton, ON, Canada; 2Department of Outcomes Research, Anesthesiology Institute, Cleveland Clinic, Cleveland, OH, USA; 3Population Health Research Institute, Hamilton, ON, Canada; 4Department of Surgery, St Joseph’s Healthcare Hamilton, Hamilton, ON, Canada; 5Acute Pain Service, St. Joseph Healthcare Hamilton, Hamilton, ON, Canada; 6Departments of Anesthesiology and Perioperative Medicine, Biomedical and Molecular Sciences, Centre for Neuroscience Studies and School of Policy Studies, Queen’s University, Kingston, ON, Canada; 7Section of Surgical Pathophysiology, Rigshospitalet, Copenhagen, Denmark; 8Department of Surgery, McMaster University, Hamilton, ON, Canada; 9Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, CanadaCorrespondence: Harsha ShanthannaDepartment of Anesthesia, McMaster University, 1280 Main St. W., Hamilton, Ontario L8S 4K1, CanadaTel +1 905-525-9140 ext. 21737Fax +1 905-523-1224Email shanthh@mcmaster.caPurpose: We conducted a feasibility 2× 2 factorial trial comparing N-methyl-D-aspartate (NMDA) antagonists (intravenous ketamine and oral memantine) versus placebo and intravenous steroids versus placebo, in patients having elective video-assisted thoracic surgery lobectomies, at St. Joseph’s Hamilton, Canada, and Cleveland Clinic, Cleveland, USA. Our feasibility objectives were: 1) recruitment rate/week; 2) recruitment of ≥ 90% of eligible patients; and 3) > 90% follow-up. Secondary objectives were incidence and intensity of persistent post-surgical pain (PPSP) and other clinical and safety outcomes.Methods: Using computerized randomization, patients were allocated to one of four groups: NMDA active with steroid placebo; NMDA placebo with steroid active; both NMDA and steroid active; both NMDA and steroid placebo. Patients, health providers, and data analysts were blinded to allocation. Patients were followed for 3 months after randomization.Results: The trial was initiated in May 2017 at Hamilton and, after subsequent regulatory and ethics approval, in April 2018 at Cleveland. The trial had to be stopped after only 1 month of recruitment in Cleveland because the packaged study medications (memantine) expired and we were unable to procure the dosage required. Among 41 eligible patients, 27 (66%) were randomized. The recruitment rate/week was 0.63, 95% confidence interval (CI): 0.47– 0.79 in Hamilton; and 1, 95% CI: 0.83– 1.17 in Cleveland. Follow-up was complete for all 24 patients (100%) in Hamilton, and 3 of 4 patients in Cleveland. In total, only 4 patients (15%), and 2 patients (7%) had persistent pain at rest and with movement, respectively. There were no significant differences between groups for other outcomes.Conclusion: The trial had to be stopped prematurely due to non-availability of study medications. Trial feasibility objectives of recruiting 90% of eligible patients and recruiting at least one patient/week per site were not met. Consideration for protocol changes will be necessary for the full trial.Trial Registration: NCT02950233.Keywords: persisting pain, chronic pain, prevention, NMDA antagonists, steroids, ketamine

Lawrence Mbuagbaw, 1–3 Laura N Anderson, 1 Cynthia Lokker, 1 Lehana Thabane 1, 2, 4 1Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, ON, Canada; 2Biostatistics Unit, St Joseph Healthcare - Hamilton, Hamilton, ON, Canada; 3Centre for Development of Best Practices in Health, Yaoundé Central Hospital, Yaoundé, Cameroon; 4Departments of Paediatrics and Anaesthesia, McMaster University, Hamilton, ON, CanadaCorrespondence: Lawrence MbuagbawBiostatistics Unit/FSORC, 50 Charlton Avenue East, St Joseph’s Healthcare - Hamilton, 3rd Floor Martha Wing, Room H321, Hamilton, ON L8N 4A6, CanadaTel +1-905-522-1155 ext 35929Email mbuagblc@mcmaster.caAbstract: Junior faculty in many universities must go through the promotion process to advance from entry level, e.g., assistant professorship to associate Professor, and ultimately to professorship. The process may often be stressful for some junior faculty, mostly due to some uncertainty about how to optimise their chances of successful promotion. In this paper, we summarise some strategies that would enhance their chances of a smooth promotion based on experiences from junior faculty and senior faculty who have served on tenure and promotion committees. These strategies include understanding the promotion process at your institution; optimizing publications as first or senior author, securing research funding as principal investigator, teaching effectively, providing service efficiently; developing good time management and priority setting skills, finding excellent mentors, and targeting opportunities for collaboration. We also encourage junior faculty to be pro-active about promotion.Keywords: junior faculty, advancement, promotion, academic, research, publishing, mentorship

Janatani Balakumaran,*,1,2 Yun-Ya Kao,*,1,2 Kuan-Wen Wang,1,2 Gabriel M Ronen,1 James MacKillop,3 Lehana Thabane,1,4–7 M Constantine Samaan1,2,41Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada; 2Division of Pediatric Endocrinology, McMaster Children’s Hospital, Hamilton, Ontario, Canada; 3Department of Psychiatry and Behavioural Neurosciences, Faculty of Health Sciences, Peter Boris Centre for Addictions Research, McMaster University/St. Joseph’s Healthcare Hamilton, Hamilton, Ontario, Canada; 4Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Ontario, Canada; 5Department of Anesthesia, McMaster University, Hamilton, Ontario, Canada; 6Centre for Evaluation of Medicines, St. Joseph’s Health Care, Hamilton, Ontario, Canada; 7Biostatistics Unit, St Joseph’s Healthcare-Hamilton, Hamilton, Ontario, CanadaCorrespondence: M Constantine SamaanDepartment of Pediatrics, McMaster University, Division of Pediatric Endocrinology, McMaster Children’s Hospital, 1280 Main Street West, HSC-3A57, Hamilton, Ontario L8S 4K1, CanadaTel +1 905 521 2100 ext. 75926Fax +1 905 308 7548Email samaanc@mcmaster.ca*These authors contributed equally to this workBackground: The obesity and Type 2 Diabetes Mellitus (T2DM) rates are at an all-time high globally. This diabesity epidemic is increasingly impacting children and adolescents, and there is scarce evidence of interventions with favourable long-term outcomes.Purpose: In order to understand the determinants of diabesity and how to address them, multiple stakeholders were invited to a meeting to discuss current state of knowledge and to help design a program to prevent pediatric and adolescent diabesity.Participants and methods: The meeting was held at McMaster University on March 4th, 2015. The event involved presentations to deliver state-of-the-art knowledge about diabesity, and roundtable discussions of several domains including nutrition, physical activity, sleep, and mental health. Discussion transcripts were analyzed using NVivo.Results: Forty-nine participants took part in the workshop. They included clinical healthcare professionals, public health, Aboriginal Patient Navigator, research scientists, students, and patients with family members. A total of 628 reference counts from the roundtable discussions were coded under 20 emerging themes. Participants believed that the most important elements of the program involve the provision of knowledge and education, family involvement, patient motivation, location of program delivery, and use of surveys and questionnaires for outcome measurement.Conclusion: Effective pediatric and adolescent diabesity prevention programs should be conceptualized by multidisciplinary stakeholders and embrace the complexity of diabesity with multiprong interventions. This meeting provided a framework for developing such interventions.Keywords: diabesity, meeting, pediatric, adolescent, obesity, pediatric type 2 diabetes mellitus

Sondra Song Jie Chen,1,2 Ajantha Nadarajah,1,2 Laura Banfield,3 Adam Fleming,1,4 Lehana Thabane,5–8 Carol Portwine,1,4 M Constantine Samaan1–2,51Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada; 2Division of Pediatric Endocrinology, McMaster Children’s Hospital, Hamilton, Ontario, Canada; 3Health Sciences Library, McMaster University, Hamilton, Ontario, Canada; 4Division of Pediatric Hematology/Oncology, McMaster Children’s Hospital, Hamilton, Ontario, Canada; 5Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Ontario, Canada; 6Department of Anesthesia, McMaster University, Hamilton, Ontario, Canada; 7Centre for Evaluation of Medicines, St Joseph’s Health Care, Hamilton, Ontario, Canada; 8Biostatistics Unit, St Joseph’s Healthcare, Hamilton, Ontario, CanadaObjectives: The number of children who survive cancer is reaching new record levels, thanks to improved management strategies. However, this population is predisposed to chronic health conditions including cardiovascular disease and type 2 diabetes, yet the full scale of these diagnoses in this population is unclear. This protocol describes the conduct of a systematic review to report on the prevalence of diabetes mellitus (DM) subtypes in childhood cancer survivors.Methods: Searches will be conducted in MEDLINE, Embase, CINAHL, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials. We will also search gray literature in Theses A&I, ProQuest Dissertations, and Web of Science as well as clinicaltrials.gov. Screening search results and data abstraction will be done independently by two reviewers. We will conduct a meta-analysis if two studies have similar designs, populations, methods, and outcome measures reported.Results: The findings of this systematic review will provide insights into the scale of diabetes in childhood cancer survivors to allow the prioritization of subpopulations that need specific interventions to screen, prevent, and treat DM. This will likely lead to improved outcomes in childhood cancer survivors.Keywords: systematic review protocol, childhood cancer, cancer survivorship, diabetes mellitus, type 1 diabetes mellitus, type 2 diabetes mellitus

Milena Cioana,1,2 Devin Peterson,3 Paul Missiuna,3 Ron El-Hawary,4 Timothy Carey,5,6 Murray A Potter,7 Laura Banfield,8 Lehana Thabane,9–12 M Constantine Samaan1,2,9 1Department of Pediatrics, McMaster University, Hamilton, ON, Canada; 2Division of Pediatric Endocrinology, McMaster Children’s Hospital, Hamilton, ON, Canada; 3Division of Orthopedics, Department of Surgery, McMaster University, Hamilton, ON, Canada; 4Orthopedic Surgery Department, IWK Children’s Health Center, Dalhousie University, Halifax, NS, Canada; 5Department of Pediatrics, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, Canada; 6Department of Surgery, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada; 7Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada; 8Health Sciences Library, McMaster University, Hamilton, ON, Canada; 9Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, ON, Canada; 10Department of Anesthesia, McMaster University, Hamilton, ON, Canada; 11Centre for Evaluation of Medicines, St Joseph’s Health Care, Hamilton, ON, Canada; 12Biostatistics Unit, St Joseph’s Healthcare-Hamilton, Hamilton, ON, Canada Abstract: In this report, we document the discussions and recommendations of a national conference designed to create a coalition to tackle adolescent idiopathic scoliosis (AIS) held on June 6 and 7, 2017 in Hamilton, ON, Canada. The goal of the establishment of this coalition is to join the efforts of patients, parents, physicians, researchers and other stakeholders to identify stakeholders’ perspectives and to categorize gaps in knowledge and target further AIS research and clinical care priorities. The participants’ main priorities included focus on shared decision making regarding clinical and research priorities between the stakeholders on the clinical, research and policy sides with patients and families. In addition, improvements in the dissemination of information via digital platforms and identification of cost-effective screening strategies that may help early identification and intervention were also recognized as a priority. Commitment was reached to form a national coalition to understand the determinants of this condition and enhance patient outcomes through improved clinical care and research efforts. Keywords: adolescent idiopathic scoliosis, childhood scoliosis, coalition, pediatric

E Danielle Sims,1–3 Sama Anvari,1,2,4,* Yung Lee,1,2,4,* Zainab Samaan,5 Laura Banfield,6 Lehana Thabane,1,7–10 M Constantine Samaan1–4,7 1Department of Pediatrics, McMaster University, Hamilton, ON, Canada; 2Division of Pediatric Endocrinology, McMaster Children’s Hospital, Hamilton, ON, Canada; 3Medical Sciences Graduate Program, McMaster University, Hamilton, ON, Canada; 4Michael G. De Groote School of Medicine, McMaster University, Hamilton, ON, Canada; 5Department of Psychiatry and Neurobehavioral Sciences, McMaster University, Hamilton, ON, Canada; 6Health Sciences Library, McMaster University, Hamilton, ON, Canada; 7Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, ON, Canada; 8Department of Anesthesia, McMaster University, Hamilton, ON, Canada; 9Centre for Evaluation of Medicines, Hamilton, ON, Canada; 10Biostatistics Unit, St. Joseph’s Healthcare, Hamilton, ON, Canada *These authors contributed equally to this work Purpose: Several countries are legalizing the use of medicinal cannabis and easing restrictions on its recreational use. While adults have been the primary target of these initiatives, expanding access to cannabis will likely lead to increased use by children. While the effects of cannabis on pediatric neuropsychological and mental health outcomes have been broadly studied, there are limited data on the physical health effects of cannabis, including endocrine health. Animal studies have shown that chronic cannabis use leads to delayed sexual maturation; however, its effects on pubertal outcomes in children are not well studied. This systematic review aimed to assess the effect of cannabis use on pubertal timing and tempo in children.Methods: We conducted a systematic review with literature searches in MEDLINE, Embase, Cochrane Database of Systematic Reviews, Central, PsycINFO, CINAHL, Web of Science, and SPORTDiscus from inception to February 2018. A gray literature search was also completed in Clinicaltrials.gov and ProQuest Dissertations and Theses A&I. The primary outcome was pubertal timing, while secondary outcomes included pubertal tempo and final height and weight. We had no restrictions on date or language of publication of papers. Two reviewers independently assessed records for eligibility, with a third reviewer resolving disagreements.Results: Our database and gray literature searches identified 759 records. A total of 29 full-text papers were assessed for eligibility. However, all studies were ultimately excluded as they did not meet the eligibility criteria.Conclusion: Our results highlight a significant gap in existing literature regarding the effects of cannabis use on puberty. Adequately powered longitudinal studies are urgently needed to provide pediatricians and other health care providers with high-quality information on the potential effects of cannabis on the physical health of children.Prospective Registrar of Systematic Reviews Registration: PROSPERO no.: CRD42018089397. Keywords: marijuana, puberty, children, pediatric, tetrahydrocannabinol, cannabis

Sandra L Carroll,1–3 Gayathri Embuldeniya,3 Jasprit Pannag,1 Krystina B Lewis,4 Jeff S Healey,2,3,5 Michael McGillion,1,2 Lehana Thabane,2,6,7 Dawn Stacey4,8 1School of Nursing, McMaster University, Hamilton, ON, Canada; 2Population Health Research Institute, Hamilton Health Sciences, Hamilton, ON, Canada; 3Hamilton Health Sciences, Hamilton, ON, Canada; 4School of Nursing, University of Ottawa, Ottawa, ON, Canada; 5Department of Medicine, McMaster University, Hamilton, ON, Canada; 6Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, ON, Canada; 7Biostatistics Unit, St. Joseph’s Healthcare, Hamilton, ON, Canada; 8Ottawa Hospital Research Institute, Ottawa, ON, Canada Purpose: Patients’ values are a key component of patient-centered care and shared decision making in health care organizations. There is limited understanding on how patients’ values guide their health related decision making or how patients understand the concept of values during these processes. This study investigated patients’ understanding of their values in the context of considering the risks/benefits of receiving an implantable cardioverter-defibrillator (ICD). Patients and methods: A qualitative substudy was conducted within a feasibility trial with first-time ICD candidates randomized to receive a patient decision aid or usual care prior to specialist consultation. Semi-structured interviews were conducted with participants post-implantation or post-specialist consultation. Results: Sixteen patients (ten male) aged 47–87 years participated. Of these, ten (62.5%) received the patient decision aid prior to specialist consultation. Findings revealed patients were confused by the word “values” and had difficulty expressing values related to risks/benefits during ICD decision making. When probed, values were conceptualized broadly capturing other factors such as desire to live, good quality of life, family’s views, ICD information, control over decision, and medical authority. Conclusion: This study revealed the difficulty patients considering an ICD had with articulating their values in the context of an ICD health decision and highlighted the challenge to effectively elicit patients’ values within health decisions overall. It is suggested that there should be a shift away from the use of the word “values” when speaking directly to patients toward language such as “what matters to you the most” or “what is most important to you”. Keywords: values, patient preferences, patient engagement, qualitative, health decision

Yanling Jin,1,* Nitika Sanger,2,* Ieta Shams,3,* Candice Luo,4,* Hamnah Shahid,5,* Guowei Li,1,* Meha Bhatt,1 Laura Zielinski,6 Bianca Bantoto,7 Mei Wang,1 Luciana PF Abbade,8 Ikunna Nwosu,4 Alvin Leenus,1 Lawrence Mbuagbaw,1 Muhammad Maaz,1 Yaping Chang,1 Guangwen Sun,1 Mitchell AH Levine,1,9 Jonathan D Adachi1,9 Lehana Thabane,1,9 Zainab Samaan1,10 1Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, ON, Canada; 2Department of Medical Science, Medical Sciences Graduate Program, McMaster University, Hamilton, ON, Canada; 3Department of Psychology, Neuroscience and Behaviour, McMaster University, Hamilton, ON, Canada; 4Faculty of Health Sciences, Bachelors of Health Sciences, McMaster University, Hamilton, ON, Canada; 5Department of Arts and Science, McMaster University, Hamilton, ON, Canada; 6Department of Neuroscience, McMaster Integrative Neuroscience Discovery and Study, McMaster University, Hamilton, ON, Canada; 7Department of Science, Honours Integrated Sciences Program, McMaster University, Hamilton, ON, Canada; 8Department of Dermatology and Radiotherapy, Botucatu Medical School, Universidade Estadual Paulista, UNESP, São Paulo, Brazil; 9St. Joseph’s Healthcare Hamilton, Hamilton, ON, Canada; 10Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, ON, Canada *These authors contributed equally to this work Purpose: Reporting guidelines (eg, Consolidated Standards of Reporting Trials [CONSORT] statement) are intended to improve reporting standards and enhance the transparency and reproducibility of research findings. Despite accessibility of such guidelines, researchers are not required to adhere to them. Our goal was to determine the current status of reporting quality in the medical literature and examine whether adherence of reporting guidelines has improved since the inception of reporting guidelines. Materials and methods: Eight reporting guidelines, such as CONSORT, Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), STrengthening the Reporting of OBservational studies in Epidemiology (STROBE), Quality of Reporting of Meta-analysis (QUOROM), STAndards for Reporting of Diagnostic accuracy (STARD), Animal Research: Reporting In Vivo Experiments (ARRIVE), Consolidated Health Economic Evaluation Reporting Standards (CHEERS), and Meta-analysis of Observational Studies in Epidemiology (MOOSE) were examined. Our inclusion criteria included reviews published between January 1996 to September 2016 which investigated the adherence to reporting guidelines in the literature that addressed clinical trials, systematic reviews, observational studies, meta-analysis, diagnostic accuracy, economic evaluations, and preclinical animal studies that were in English. All reviews were found on Web of Science, Excerpta Medical Database (EMBASE), MEDLINE, and Cumulative Index to Nursing and Allied Health Literature (CINAHL). Results: Among the general searching of 26,819 studies by using the designed searching method, 124 studies were included post screening. We found that 87.9% of the included studies reported suboptimal adherence to reporting guidelines. Factors associated with poor adherence included non-pharmacological interventions, year of publication, and trials concluding with significant results. Improved adherence was associated with better study designs such as allocation concealment, random sequence, large sample sizes, adequately powered studies, multiple authorships, and being published in journals endorsing guidelines. Conclusion: We conclude that the level of adherence to reporting guidelines remains suboptimal. Endorsement of reporting guidelines by journals is important and recommended. Keywords: guidelines, adherence, review, CONSORT

Lawrence Mbuagbaw,1–3 Amy L Slogrove,4,5 Jacqueline Sas,6 John Lengwe Kunda,7 Frederick Morfaw,8 Jackson K Mukonzo,9 Wei Cao,10–12 Gisele Ngomba-Kadima,13 Moleen Zunza,14,15 Pierre Ongolo-Zogo,3 Philip N Nana,8 Anne Cockcroft,16,17 Neil Andersson,16,18,19 Nelson Sewankambo,9 Mark F Cotton,4 Taisheng Li,12 Taryn Young,14 Joel Singer,5,6 Jean-Pierre Routy,6,10,11,20 Colin JD Ross,21 Kyaw Thin,22 Lehana Thabane,1,2,6,23–25 Aslam H Anis5,6 1Department of Health Research Methods, Evidence and Impact, McMaster University, 2Biostatistics Unit, Father Sean O’Sullivan Research Centre, St Joseph’s Healthcare Hamilton, Hamilton, ON, Canada; 3Centre for Development of Best Practices in Health, Yaoundé Central Hospital, Yaoundé, Cameroon; 4Department of Paediatrics and Child Health, Family Clinical Research Unit (FAM-CRU), Stellenbosch University, Tygerberg, South Africa; 5UBC School of Population and Public Health, Vancouver, BC, 6CIHR Canadian HIV Trials Network, UBC, Canada; 7Community Information and Epidemiological Technologies (CIET), Lusaka, Zambia; 8Department of Obstetrics and Gynaecology, Faculty of Medicines and Biomedical Sciences, University of Yaoundé 1, Yaoundé, Cameroon; 9School of Biomedical Sciences, College of Health Sciences, University of Makerere, Kampala, Uganda; 10Chronic Viral Illness Service, McGill University Health Centre, 11Research Institute of the McGill University Health Centre, Montreal, QC, Canada; 12Department of Infectious Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China; 13Queen Mamahato Memorial Hospital, Maseru, Lesotho; 14Centre for Evidence-based Health Care, Faculty of Health Sciences, Stellenbosch University, Tygerberg, South Africa; 15Research Institute, McGill University Health Centre, Montreal, QC, Canada; 16Community Information and Epidemiological Technologies (CIET) Trust Botswana, Gaborone, Botswana; 17Community Information and Epidemiological Technologies – Participatory Research at McGill (CIET-PRAM), Department of Family Medicine, McGill University, 18Centro de Investigación de Enfermedades Tropicales, Universidad Autónoma de Guerrero, Chilpancingo, Mexico; 19Department of Family Medicine, McGill University, Montreal, Canada; 20Division of Hematology, McGill University Health Centre, Montreal, QC, Canada; 21Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC, Canada; 22Research Coordination Unit, Ministry of Health and Social Welfare, Maseru, Lesotho; 23Departments of Paediatrics and Anaesthesia, McMaster University, Hamilton, ON, Canada; 24Centre for Evaluation of Medicine, St Joseph’s Healthcare—Hamilton, ON, Canada; 25Population Health Research Institute, Hamilton Health Sciences, Hamilton, ON, Canada Abstract: As a response to the human immunodeficiency virus (HIV) epidemic and part of ­Canadian Institutes for Health Research’s mandate to support international health research capacity building, the Canadian Institutes for Health Research Canadian HIV Trial Network (CTN) developed an international postdoctoral fellowship award under the CTN’s Postdoctoral Fellowship Awards Program to support and train young HIV researchers in resource-limited settings. Since 2010, the fellowship has been awarded to eight fellows in Cameroon, China, Lesotho, South Africa, Uganda and Zambia. These fellows have conducted research on a wide variety of topics and have built a strong network of collaboration and scientific productivity, with 40 peer-reviewed publications produced by six fellows during their fellowships. They delivered two workshops at international conferences and have continued to secure funding for their research, using the fellowship as a stepping stone. The CTN has been successful in building local HIV research capacity and forming a strong network of like-minded junior low- and middle-income country researchers with high levels of research productivity. They have developed into mentors, supervisors and faculty members, who, in turn, build local capacity. The sustainability of this international fellowship award relies on the recognition of its strengths and the involvement of other stakeholders for additional resources. Keywords: CTN, postdoctoral fellowship, capacity building, clinical trials, networking

Guowei Li,1–3 Yanling Jin,1 Lawrence Mbuagbaw,1,2 Lisa Dolovich,1,2,4 Jonathan D Adachi,2,5 Mitchell AH Levine,1–3,5 Deborah Cook,1,2,5 Zainab Samaan,1,2 Lehana Thabane1,2 1Department of Health Research Methods, Impact and Evidence, McMaster University, Hamilton, ON, Canada; 2St. Joseph’s Healthcare Hamilton, McMaster University, Hamilton, ON, Canada; 3Centre for Evaluation of Medicines, Programs for Assessment of Technology in Health (PATH) Research Institute, McMaster University, Hamilton, ON, Canada; 4Department of Family Medicine, McMaster University, Hamilton, ON, Canada; 5Department of Medicine, McMaster University, Hamilton, ON, Canada Background: Disseminating research protocols, processes, methods or findings via peer-reviewed publications has substantive merits and benefits to various stakeholders. Purpose: In this article, we share strategies to enhance research publication contents (ie, what to write about) and to facilitate scientific writing (ie, how to write) in health research collaborations. Methods: Empirical experience sharing. Results: To enhance research publication contents, we encourage identifying appropriate opportunities for publications, publishing protocols ahead of results papers, seeking publications related to methodological issues, considering justified secondary analyses, and sharing academic process or experience. To advance writing, we suggest setting up scientific writing as a goal, seeking an appropriate mentorship, making full use of scientific meetings and presentations, taking some necessary formal training in areas such as effective communication and time and stress management, and embracing the iterative process of writing. Conclusion: All the strategies we share are dependent upon each other; and they advocate gradual academic accomplishments through study and training in a “success-breeds-success” way. It is expected that the foregoing shared strategies in this paper, together with other previous guidance articles, can assist one with enhancing research publications, and eventually one’s academic success in health research collaborations. Keywords: research publication, scientific writing, health research collaboration

Guowei Li,1–3 Mariam Kamel,1 Yanling Jin,1 Michael Kuan Xu,1 Lawrence Mbuagbaw,1,2 Zainab Samaan,1,4 Mitchell AH Levine,1–4 Lehana Thabane1,2 1Department of Health Research Methods, Evidence, and Impact, 2St. Joseph’s Healthcare Hamilton, 3Centre for Evaluation of Medicines, Programs for Assessment of Technology in Health Research Institute, 4Department of Medicine, McMaster University, Hamilton, ON, Canada Aim: Article retraction is a measure taken by journals or authors where there is evidence of research misconduct or error, redundancy, plagiarism or unethical research. Recently, the retraction of scientific publications has been on the rise. In this survey, we aimed to describe the characteristics and distribution of retracted articles and the reasons for retractions.Methods: We searched retracted articles on the PubMed database and Retraction Watch website from 1980 to February 2016. The primary outcomes were the characteristics and distribution of retracted articles and the reasons for retractions. The secondary outcomes included how article retractions were handled by journals and how to improve the journal practices toward article retractions.Results: We included 1,339 retracted articles. Most retracted articles had six authors or fewer. Article retraction was most common in the USA (26%), Japan (11%) and Germany (10%). The main reasons for article retraction were misconduct (51%, n = 685) and error (14%, n = 193). There were 66% (n = 889) of retracted articles having male senior or corresponding authors. Of the articles retracted after August 2010, 63% (n = 567) retractions were reported on Retraction Watch. Large discrepancies were observed in the ways that different journals handled article retractions. For instance, articles were completely withdrawn from some journals, while in others, articles were still available with no indication of retraction. Likewise, some retraction notices included a detailed account of the events that led to article retraction, while others only consisted of a statement indicating the article retraction.Conclusion: The characteristics, geographic distribution and reasons for retraction of published articles involving human research participants were examined in this survey. More efforts are needed to improve the consistency and transparency of journal practices toward article retractions. Keywords: article retraction, research misconduct, research ethics, journal policy

Tea Rosic,1 Leen Naji,2 Monica Bawor,3 Brittany B Dennis,3 Carolyn Plater,4 David C Marsh,5 Lehana Thabane,6–8 Zainab Samaan6–11 1St Joseph’s Healthcare, 2Michael G DeGroote School of Medicine, McMaster University, Hamilton, ON, Canada; 3St George’s University of London, London, UK; 4Canadian Addiction Treatment Centre, Richmond Hill, 5Northern Ontario School of Medicine, Sudbury, 6Biostatistics Unit, Research Institute, St Joseph’s Healthcare, 7Department of Clinical Epidemiology and Biostatistics, McMaster University, 8Peter Boris Centre for Addictions Research, 9Mood Disorders Research Unit, St Joseph’s Healthcare, 10Population Genomics Program, Chanchlani Research Centre, 11Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, ON, Canada Objective: There is a significant interindividual variability in treatment outcomes in methadone maintenance treatment (MMT) for opioid use disorder (OUD). This prospective cohort study examines the impact of comorbid psychiatric disorders on continued illicit opioid use in patients receiving MMT for OUD. Methods: Data were collected from 935 patients receiving MMT in outpatient clinics between June 2011 and June 2015. Using linear regression analysis, we evaluated the impact of having a comorbid psychiatric disorder on continued illicit opioid use during MMT, adjusting for important confounders. The main outcome measure was percentage of opioid-positive urine screens for 6 months. We conducted a subgroup analysis to determine the influence of specific comorbid psychiatric disorders, including substance use disorders, on continued illicit opioid use. Results: Approximately 80% of participants had at least one comorbid psychiatric disorder in addition to OUD, and 42% of participants had a comorbid substance use disorder. There was no significant association between having a psychiatric comorbidity and continuing opioid use (P=0.248). Results from subgroup analysis, however, suggest that comorbid tranquilizer (β=20.781, P

Ji Cheng,1,2 Alfonso Iorio,2,3 Maura Marcucci,4 Vadim Romanov,5 Eleanor M Pullenayegum,6,7 John K Marshall,3,8 Lehana Thabane1,2 1Biostatistics Unit, St Joseph’s Healthcare Hamilton, 2Department of Clinical Epidemiology and Biostatistics, 3Department of Medicine, McMaster University, Hamilton, ON, Canada; 4Geriatrics, Fondazione Ca’ Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy; 5Baxter HealthCare, Global Medical Affairs, Westlake Village, CA, USA; 6Child Health Evaluation Sciences, Hospital for Sick Children, 7Dalla Lana School of Public Health, University of Toronto, Toronto, 8Division of Gastroenterology, Hamilton Health Science, Hamilton, ON, Canada Background: Developing inhibitors is a rare event during the treatment of hemophilia A. The multifacets and uncertainty surrounding the development of inhibitors further complicate the process of estimating inhibitor rate from the limited data. Bayesian statistical modeling provides a useful tool in generating, enhancing, and exploring the evidence through incorporating all the available information.Methods: We built our Bayesian analysis using three study cases to estimate the inhibitor rates of patients with hemophilia A in three different scenarios: Case 1, a single cohort of previously treated patients (PTPs) or previously untreated patients; Case 2, a meta-analysis of PTP cohorts; and Case 3, a previously unexplored patient population – patients with baseline low-titer inhibitor or history of inhibitor development. The data used in this study were extracted from three published ADVATE (antihemophilic factor [recombinant] is a product of Baxter for treating hemophilia A) post-authorization surveillance studies. Noninformative and informative priors were applied to Bayesian standard (Case 1) or random-effects (Case 2 and Case 3) logistic models. Bayesian probabilities of satisfying three meaningful thresholds of the risk of developing a clinical significant inhibitor (10/100, 5/100 [high rates], and 1/86 [the Food and Drug Administration mandated cutoff rate in PTPs]) were calculated. The effect of discounting prior information or scaling up the study data was evaluated.Results: Results based on noninformative priors were similar to the classical approach. Using priors from PTPs lowered the point estimate and narrowed the 95% credible intervals (Case 1: from 1.3 [0.5, 2.7] to 0.8 [0.5, 1.1]; Case 2: from 1.9 [0.6, 6.0] to 0.8 [0.5, 1.1]; Case 3: 2.3 [0.5, 6.8] to 0.7 [0.5, 1.1]). All probabilities of satisfying a threshold of 1/86 were above 0.65. Increasing the number of patients by two and ten times substantially narrowed the credible intervals for the single cohort study (1.4 [0.7, 2.3] and 1.4 [1.1, 1.8], respectively). Increasing the number of studies by two and ten times for the multiple study scenarios (Case 2: 1.9 [0.6, 4.0] and 1.9 [1.5, 2.6]; Case 3: 2.4 [0.9, 5.0] and 2.6 [1.9, 3.5], respectively) had a similar effect.Conclusion: Bayesian approach as a robust, transparent, and reproducible analytic method can be efficiently used to estimate the inhibitor rate of hemophilia A in complex clinical settings. Keywords: inhibitor rate, meta-analysis, multicentric study, Bayesian, hemophilia A

Alex Thabane,1,2 Brittany B Dennis,3,4 Olga Gajic-Veljanoski,3,9,10 James Paul,2,3 Lehana Thabane2,3,5-8 1Life Sciences Program, Queen’s University, Kingston, ON, Canada; 2Department of Anesthesia, McMaster University Hamilton ON, 3Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton ON, Canada; 4St. George’s University of London, London England, UK; 5Population Health Research Institute, Hamilton Health Sciences, 6Department of Pediatrics, McMaster University, Hamilton, ON, Canada; 7Centre for Evaluation of Medicine, 8Biostatistics Unit, Father Sean O’Sullivan Research Centre, St Joseph’s Healthcare, Hamilton, ON, Canada; 9Department of Medicine, McMaster University, Hamilton ON, Canada; 10Hamilton Health Sciences, St. Peter’s Hospital, Hamilton, ON Canada Background: Stepped wedge design (SWD) is a cluster randomized controlled trial (RCT) design that sequentially rolls out intervention to all clusters at varying time points. Being a relatively new design method, reporting quality has yet to be explored, and this review will seek to fill this gap in knowledge. Objectives: The objectives of this review are: 1) to assess the quality of SWD trial reports based on the CONSORT guidelines or CONSORT extension to cluster RCTs; 2) to assess the completeness of reporting of SWD trial abstracts using the CONSORT extension for abstracts; 3) to assess the reporting of sample size details in SWD trial reports or protocols; 4) to assess the completeness of reporting of SWD trial protocols according to SPIRIT guidelines; 5) to assess the consistency between the trial registration information and final SWD trial reports; and 6) to assess the consistency of what is reported in the abstracts and main text of the SWD trial reports. We will also explore factors that are associated with the completeness of reporting. Methods: We will search MEDLINE, EMBASE, Web of Science, CINAHL, and PsycINFO for all randomized controlled trials utilizing SWD. Details from eligible papers will be extracted in duplicate. Demographic statistics obtained from the data extraction will be analyzed to answer the primary objectives pertaining to the reporting quality of several aspects of a published paper, as well as to explore possible temporal trends and consistency between abstracts, trial registration information, and final published articles. Discussion: Findings from this review will establish the reporting quality of SWD trials and inform academics and clinicians on their completeness and consistency. Results of this review will influence future trials and improve the overall quality and reporting of SWD trials. Keywords: randomized controlled trial, stepped wedge design, stepped wedge, cluster randomized trial, quality of reporting, systematic review

Shiyuan Zhang,1 James Paul,2 Manyat Nantha-Aree,2 Norman Buckley,2 Uswa Shahzad,2 Ji Cheng,2 Justin DeBeer,5 Mitchell Winemaker,5 David Wismer,5 Dinshaw Punthakee,5 Victoria Avram,5 Lehana Thabane1–4 1Department of Clinical Epidemiology and Biostatistics, McMaster University, 2Department of Anesthesia, McMaster University, 3Biostatistics Unit/Centre for Evaluation of Medicines, St Joseph’s Healthcare-Hamilton, 4Population Health Research Institute, Hamilton Health Science/McMaster University, 5Department of Surgery, Division of Orthopaedics, McMaster University, Hamilton, ON, Canada Background: Postoperative pain management in total joint replacement surgery remains ineffective in up to 50% of patients and has an overwhelming impact in terms of patient well-being and health care burden. We present here an empirical analysis of two randomized controlled trials assessing whether addition of gabapentin to a multimodal perioperative analgesia regimen can reduce morphine consumption or improve analgesia for patients following total joint arthroplasty (the MOBILE trials). Methods: Morphine consumption, measured for four time periods in patients undergoing total hip or total knee arthroplasty, was analyzed using a linear mixed-effects model to provide a longitudinal estimate of the treatment effect. Repeated-measures analysis of variance and generalized estimating equations were used in a sensitivity analysis to compare the robustness of the methods. Results: There was no statistically significant difference in morphine consumption between the treatment group and a control group (mean effect size estimate 1.0, 95% confidence interval −4.7, 6.7, P=0.73). The results remained robust across different longitudinal methods. Conclusion: The results of the current reanalysis of morphine consumption align with those of the MOBILE trials. Gabapentin did not significantly reduce morphine consumption in patients undergoing major replacement surgeries. The results remain consistent across longitudinal methods. More work in the area of postoperative pain is required to provide adequate management for this patient population. Keywords: postoperative morphine consumption, randomized controlled trials, gabapentin, reanalysis

Brittany B Dennis,1 M Constantine Samaan,2 Monica Bawor,3 James Paul,4 Carolyn Plater,5 Guillaume Pare,1 Andrew Worster,6 Michael Varenbut,5 Jeff Daiter,5 David C Marsh,5,7 Dipika Desai,8 Lehana Thabane,1,9,10 Zainab Samaan1,8,11 1Department of Clinical Epidemiology and Biostatistics, 2Department of Pediatrics, Division of Pediatric Endocrinology, 3McMaster Integrative Neuroscience Discovery and Study Program, 4Department of Anesthesia, McMaster University, Hamilton, 5Ontario Addiction Treatment Centres, Richmond Hill, 6Department of Medicine, Hamilton General Hospital, Hamilton, 7Northern Ontario School of Medicine, Sudbury, 8Population Genomics Program, Chanchlani Research Centre, McMaster University, Hamilton, 9Centre for Evaluation of Medicine, 10System Linked Research Unit, Hamilton, 11Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, ON, Canada Background: Chronic pain is the most commonly reported comorbidity among patients with opioid addiction receiving methadone maintenance treatment (MMT), with an estimated prevalence ranging between 30% and 55%. Evidence suggests that patients with comorbid pain are at high risk for poor treatment response, including continued illicit substance use. Due to the important relationship between the presence of pain and illicit substance abuse within the MMT setting, it is imperative that we target our efforts toward understanding the characteristics of this patient population.Methods: The primary objective of this study was to explore the clinical and inflammatory profile of MMT patients reporting comorbid pain. This multicenter study enrolled patients (n=235) on MMT for the treatment of opioid dependence. Clinical history and blood and urine data were collected. Blood samples were obtained for estimating the serum levels of inflammatory markers (tumor necrosis factor [TNF]-α, interleukin-1 receptor antagonist [IL-1ra], IL-6, IL-8, IL-10, interferon [IFN]-γ and chemokine (C–C motif) ligand 2 [CCL2]). The study objectives were addressed using a descriptive statistical summary and a multivariable logistic regression model constructed in STATA version 12.Results: Among the participants eligible for inclusion (n=235), serum IFN-γ level and substance abuse behavior proved to be important delineating characteristics for the detection of comorbid pain. Analysis of inflammatory profile showed IFN-γ to be significantly elevated among patients reporting comorbid pain (odds ratio [OR]: 2.02; 95% confidence interval [CI]: 1.17, 3.50; P=0.01). Patients reporting comorbid pain were also found to have an increase in positive opioid urine screens (OR: 1.02; 95% CI: 1.00, 1.03; P=0.01), indicating an increase in illicit opioid consumption.Conclusion: MMT patients with comorbid pain were shown to have elevated IFN-γ and higher rates of continued opioid abuse. The ability to objectively distinguish between patients with comorbid pain may help to both improve the prediction of poor responders to MMT as well as identify treatment approaches such as anti-inflammatory medications as safe alternatives for MMT patients with comorbid pain. Keywords: methadone maintenance treatment, inflammatory markers, TNF-α, IFN-γ, interleukins, CCL2, Brief Pain Inventory, opioid dependence

Zainab Samaan,1–4 Monica Bawor,3,4 Brittany B Dennis,2,3 Carolyn Plater,5 Michael Varenbut,5 Jeffrey Daiter,5 Andrew Worster,5,6 David C Marsh,5,7 Charlie Tan,8 Dipika Desai,3 Lehana Thabane,2,9,10 Guillaume Pare11 1Department of Psychiatry and Behavioural Neurosciences, 2Department of Clinical Epidemiology and Biostatistics, 3Population Genomics Program, Chanchlani Research Centre, 4MiNDS Neuroscience Program, McMaster University, Hamilton, Ontario, Canada; 5Ontario Addiction Treatment Centres, Richmond Hill, Ontario, Canada; 6Department of Medicine, McMaster University, Hamilton, Ontario, Canada; 7Northern Ontario School of Medicine, Laurentian University, Sudbury, Ontario, Canada; 8Michael G. DeGroote School of Medicine, McMaster University, 9Biostatistics Unit, Centre for Evaluation of Medicine, 10System Linked Research Unit, 11Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada Introduction: Treatment of opioid addiction with methadone is effective; however, it is known to produce interindividual variability. This may be influenced in part by genetic variants, which can increase the initial risk of developing opioid addiction as well as explain differences in response to treatment. This pilot study aimed to assess the feasibility of conducting a full-scale genetic analysis to identify genes that predict methadone treatment outcomes in this population. Methods: This was a cross-sectional observational study of patients admitted to a methadone maintenance treatment program for opioid addiction. We obtained demographic and clinical characteristics in addition to blood and urine samples, for the assessment of treatment outcomes. Results: The recruitment process yielded 252 patients, representing a 20% recruitment rate. We conducted genetic testing based on a 99.6% rate of provision of DNA samples. The average retention in treatment was 3.4 years, and >50% of the participants reported psychiatric and medical comorbidities. BDNF rs6265 and DRD2 rs1799978 were the common single nucleotide polymorphisms (SNPs) selected for the feasibility study. Discussion: This study met our predetermined feasibility criteria; recruitment, response rates, and genetic testing were feasible; treatment duration was sufficient for follow up; and the prevalence of comorbid conditions indicated the need for reliable psychiatric and chronic pain measures. The study strengths included effective collaboration with clinics and the generalizability of sample population. Key learning points show the need for assessment of treatment outcomes on multiple domains, implementation of follow up, and the development of standardized training for the study clinical staff. Keywords: genetics, substitute opioid therapy, treatment response, risk factors

M Constantine Samaan,1–3 Marlie Valencia,1 Connie Cheung,1 Boguslaw Wilk,1,3 Keith Lau,1,4 Lehana Thabane1,5–8 1Department of Pediatrics, McMaster University, 2Division of Pediatric Endocrinology, 3Children's Exercise and Nutrition Center, 4Division of Pediatric Nephrology, McMaster Children's Hospital, 5Population Health Research Institute, 6Department of Clinical Epidemiology and Biostatistics, 7Department of Anesthesia, McMaster University, 8Centre for Evaluation of Medicines, Hamilton, ON, Canada Abstract: Global rates of type 2 diabetes in children and adolescents have increased significantly over the past three decades. Type 2 diabetes is a relatively new disease in this age group, and there is a dearth of information about how to structure treatment programs to manage its comorbidities and complications. In this paper, we describe the design and implementation of a personalized multidisciplinary, family-centered, pediatric and adolescent type 2 diabetes program at a tertiary pediatric center in Hamilton, Ontario, Canada. We report the process of designing and implementing such a program, and show that this multidisciplinary program led to improvement in glycated hemoglobin (n=17, 8% at baseline versus 6.4% at 1 year, 95% confidence interval (0.1–0.28), P-value

Shiyuan Zhang,1 James Paul,2 Manyat Nantha-Aree,2 Norman Buckley,2 Uswa Shahzad,2 Ji Cheng,2 Justin DeBeer,5 Mitchell Winemaker,5 David Wismer,5 Dinshaw Punthakee,5 Victoria Avram,5 Lehana Thabane1–41Department of Clinical Epidemiology and Biostatistics, 2Department of Anesthesia, McMaster University, Hamilton, ON, Canada; 3Biostatistics Unit/Centre for Evaluation of Medicines, St Joseph's Healthcare - Hamilton, Hamilton, ON, Canada; 4Population Health Research Institute, Hamilton Health Science/McMaster University, 5Department of Surgery, Division of Orthopaedics, McMaster University, Hamilton, ON, CanadaBackground: Although seemingly straightforward, the statistical comparison of a continuous variable in a randomized controlled trial that has both a pre- and posttreatment score presents an interesting challenge for trialists. We present here empirical application of four statistical methods (posttreatment scores with analysis of variance, analysis of covariance, change in scores, and percent change in scores), using data from a randomized controlled trial of postoperative pain in patients following total joint arthroplasty (the Morphine COnsumption in Joint Replacement Patients, With and Without GaBapentin Treatment, a RandomIzed ControlLEd Study [MOBILE] trials).Methods: Analysis of covariance (ANCOVA) was used to adjust for baseline measures and to provide an unbiased estimate of the mean group difference of the 1-year postoperative knee flexion scores in knee arthroplasty patients. Robustness tests were done by comparing ANCOVA with three comparative methods: the posttreatment scores, change in scores, and percentage change from baseline.Results: All four methods showed similar direction of effect; however, ANCOVA (-3.9; 95% confidence interval [CI]: -9.5, 1.6; P=0.15) and the posttreatment score (-4.3; 95% CI: -9.8, 1.2; P=0.12) method provided the highest precision of estimate compared with the change score (-3.0; 95% CI: -9.9, 3.8; P=0.38) and percent change (–0.019; 95% CI: -0.087, 0.050; P=0.58).Conclusion: ANCOVA, through both simulation and empirical studies, provides the best statistical estimation for analyzing continuous outcomes requiring covariate adjustment. Our empirical findings support the use of ANCOVA as an optimal method in both design and analysis of trials with a continuous primary outcome.Keywords: ANOVA, ANCOVA, change score, knee arthroplasty

Harsha Shanthanna,1 Philip Chan,1 James McChesney,1 Lehana Thabane,2 James Paul1 1Department of Anesthesia, 2Department of Clinical Epidemiology and Biostatistics, St Joseph's Hospital, McMaster University, Hamilton, ON, Canada Background: No proof of efficacy, in the form of a randomized controlled trial (RCT), exists to support pulsed radiofrequency (PRF) treatment of the dorsal root ganglion (DRG) for chronic lumbar radicular (CLR) pain. We determined the feasibility of a larger trial (primary objective), and also explored the efficacy of PRF in decreasing pain on a visual analog scale (VAS) and improving the Oswestry Disability Index. Methods: This was a single-center, placebo-controlled, triple-blinded RCT. Patients were randomized to a placebo group (needle placement) or a treatment group (PRF at 42°C for 120 seconds to the DRG). Patients were followed up for 3 months post procedure. Outcomes with regard to pain, Oswestry Disability Index score, and side effects were analyzed on an intention-to-treat basis. Results: Over 15 months, 350 potential patients were identified and 56 were assessed for eligibility. Fifteen of them did not meet the selection criteria. Of the 41 eligible patients, 32 (78%) were recruited. One patient opted out before intervention. Three patients were lost to follow-up at 3 months. Mean VAS differences were not significantly different at 4 weeks (-0.36, 95% confidence interval [CI], -2.29, 1.57) or at 3 months (-0.76, 95% CI, -3.14, 1.61). The difference in mean Oswestry Disability Index score was also not significantly different at 4 weeks (-2%, 95% CI, -14%, 10%) or 3 months (-7%, 95% CI, -21%, 6%). There were no major side effects. Six of 16 patients in the PRF group and three of 15 in the placebo group showed a >50% decrease in VAS score. Conclusion: The recruitment rate was partially successful. At 3 months, the relative success of PRF-DRG was small. A large-scale trial to establish efficacy is not practically feasible considering the small effect size, which would necessitate recruitment of a challengingly large number of participants over a number of years. Until clear parameters for application of PRF are established, clinicians will need to use their individual judgment regarding its clinical applicability, given the present evidence. Keywords: pulsed radiofrequency, radicular pain, dorsal root ganglion

Chenglin Ye,1,2 Gina Browne,1,3 Joseph Beyene,1 Lehana Thabane1,2 1Department of Clinical Epidemiology and Biostatistics, McMaster University, 2Biostatistcs Unit, St Joseph's Healthcare Hamilton, 3School of Nursing, McMaster University, Hamilton, ON, Canada Background: The value of integrated care through comprehensive, coordinated, and family-centered services has been increasingly recognized for improving health outcomes of children with special health care needs (CSHCN). In a randomized controlled trial (RCT), the integrated care provided through the Children's Treatment Network (CTN) was compared with usual care in improving the psychosocial health of target CSHCN. In this paper, we aimed to estimate the effect of CTN care by conducting multiple analyses to handle noncompliance in the trial. Methods: The trial recruited target children in Simcoe County and York Region, ON, Canada. Children were randomized to receive CTN or usual care and were followed for 2 years. The CTN group received integrated services through multiple providers to address their specific needs while the usual care group continued to receive care directed by their parents. The outcome was change in psychosocial quality of life at 2 years. We conducted intention-to-treat, as-treated, per-protocol, and instrumental variable analyses to analyze the outcome. Results: The trial randomized 445 children, with 229 in the intervention group and 216 in the control group. During follow-up, 52% of children in the intervention group did not receive complete CTN care for various reasons. At 2 years, we did not find a significant improvement in psychosocial quality of life among the children receiving CTN care compared with usual care (intention-to-treat mean difference 1.50, 95% confidence interval −1.49 to 4.50; P = 0.32). Other methods of analysis yielded similar results. Conclusion: Although the effect of CTN care was not significant, there was evidence showing benefits of integrated care for CSHCN. More RCTs are needed to demonstrate the magnitude of such an effect. The CTN study highlights the key challenges in RCTs when assessing interventions involving integrated care, and informs further RCTs including similar evaluations. Keywords: children with special health care needs, chronically ill, family-centered care, randomized controlled trial, noncompliance

Zainab Samaan,1–3 Lawrence Mbuagbaw,2 Daisy Kosa,2,4 Victoria Borg Debono,2,5 Rejane Dillenburg,6 Shiyuan Zhang2, Vincent Fruci,7 Brittany Dennis,2 Monica Bawor,8 Lehana Thabane2,5,91Department of Psychiatry and Behavioral Neurosciences, McMaster University, Hamilton, 2Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, 3Population Genomics Program, McMaster University, Hamilton, 4Department of Nephrology, Toronto General Hospital, Toronto, 5Department of Anesthesia, McMaster University, Hamilton, 6Department of Pediatrics, McMaster University, Hamilton, 7Michael G DeGroote School of Medicine, McMaster University, Hamilton, 8McMaster Integrative Neuroscience Discovery and Study (MiNDS) Program, McMaster University, Hamilton, 9Centre for Evaluation of Medicines, Hamilton, ON, CanadaBackground: Reporting guidelines have been available for the past 17 years since the inception of the Consolidated Standards of Reporting Trials statement in 1996. These guidelines were developed to improve the quality of reporting of studies in medical literature. Despite the widespread availability of these guidelines, the quality of reporting of medical literature remained suboptimal. In this study, we assess the current adherence practice to reporting guidelines; determine key factors associated with better adherence to these guidelines; and provide recommendations to enhance adherence to reporting guidelines for future studies.Methods: We undertook a systematic scoping review of systematic reviews of adherence to reporting guidelines across different clinical areas and study designs. We searched four electronic databases (Cumulative Index to Nursing and Allied Health Literature, Web of Science, Embase, and Medline) from January 1996 to September 2012. Studies were included if they addressed adherence to one of the following guidelines: Consolidated Standards of Reporting Trials (CONSORT), Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), Quality of Reporting of Meta-analysis (QUOROM), Transparent Reporting of Evaluations with Nonrandomized Designs (TREND), Meta-analysis Of Observational Studies in Epidemiology (MOOSE) and Strengthening the Reporting of Observational Studies in Epidemiology (STROBE). A protocol for this study was devised. A literature search, data extraction, and quality assessment were performed independently by two authors in duplicate. This study reporting follows the PRISMA guidelines.Results: Our search retrieved 5159 titles, of which 50 were eligible. Overall, 86.0% of studies reported suboptimal levels of adherence to reporting guidelines. Factors associated with better adherence included journal impact factor and endorsement of guidelines, publication date, funding source, multisite studies, pharmacological interventions and larger studies.Conclusion: Reporting guidelines in the clinical literature are important to improve the standards of reporting of clinical studies; however, adherence to these guidelines remains suboptimal. Action is therefore needed to enhance the adherence to these standards. Strategies to enhance adherence include journal editorial policies endorsing these guidelines.Keywords: scoping, systematic, review, adherence, reporting, guidelines

Lawrence Mbuagbaw,1–3 Frederick Morfaw,4 John-Eudes L Kunda,5 Jackson K Mukonzo,6 Jasmine Kastner,7 Shiyuan Zhang,2,3 Madzouka Kokolo,8 Lehana Thabane1,3,9–11 1Centre for Development of Best Practices in Health, Yaounde Central Hospital, Yaounde, Cameroon; 2Department of Clinical Epidemiology and Biostatistics, McMaster University, 3Biostatistics Unit, Father Sean O'Sullivan Research Centre, St Joseph's Healthcare, Hamilton, ON, Canada; 4Department of Obstetrics and Gynaecology, Faculty of Medicines and Biomedical Sciences, University of Yaounde 1, Yaounde, Cameroon; 5Community Information and Epidemiological Technologies, Lusaka, Zambia; 6School of Biomedical Sciences, College of Health Sciences, University of Makerere, Kampala, Uganda; 7Faculty of Health Sciences, Simon Fraser University, BC, Canada; 8Ottawa Hospital Research Institute, 9Departments of Pediatrics and Anaesthesia, McMaster University, 10Centre for Evaluation of Medicine, St Joseph's Healthcare, 11Population Health Research Institute, Hamilton Health Sciences, Hamilton, ON, Canada Abstract: Young health researchers all over the world often encounter difficulties in the early stages of their careers. Formal acquisition of research skills in academic settings does not always offer sufficient guidance to overcome these challenges. Based on the collective experiences of some young researchers and research mentors, we describe some tips for a successful health career and offer some useful resources. These tips include: institutional affiliation, early manuscript writing, early manuscript reviewing, finding a mentor, collaboration and networking, identifying sources of funding, establishing research interests, investing in research methods training, developing interpersonal and personal skills, providing mentorship, and balancing work with everyday life. The rationale behind these tips and how to achieve them is provided. Keywords: health research career, young researcher, guidance

Lawrence Mbuagbaw,1,2 Lehana Thabane2,31Centre for the Development of Best Practices in Health (CDBPH), Yaoundé Central Hospital, Henri Dunant Avenue, Messa, Yaoundé, Cameroon; 2Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, ON, Canada; 3Biostatistics Unit, Father Sean O’Sullivan Research Centre, St Joseph's Healthcare, Hamilton, ON, CanadaAbstract: Mentoring plays an important role in learning and career development. Mentored researchers are more productive and more likely to publish their work. However, mentorship programs are not universally used in most settings or disciplines. Furthermore, successful and mutually beneficial mentoring relationships are not always easy to arrange. Long-distance mentoring relationships are even more difficult to handle and may break down for a wide variety of reasons. Drawing from our experiences with the first Canadian Institutes of Health Research – Canadian HIV Trials Network international postdoctoral fellowship program, we describe the roles of the context, the key mentor and the mentee attributes; goals and expectations; environments, local support, a communication plan, funding, face-to-face contact, multidisciplinary collaboration, co-mentoring, and evaluation as they apply to the successful implementation of a long-distance mentoring program.Keywords: long distance, mentoring, framework, Canada, Cameroon

Adefowope Odueyungbo,1 Lehana Thabane21Department of Biostatistics, Vertex Pharmaceuticals, Cambridge, MA, 2Department of Clinical Epidemiology and Biostatistics, McMaster University, and Biostatistics Unit, Father Sean O'Sullivan Research Centre/Centre for Evaluation of Medicines, St Joseph's Healthcare Hamilton, ON, CanadaAbstract: Mentoring is routinely used as a tool to facilitate acquisition of skills by new professionals in fields like medicine, nursing, surgery, and business. While mentoring has been proposed as an effective strategy for knowledge and skills transfer in biostatistics and related fields, there is still much to be done to facilitate adoption by stakeholders, including academia and employers of biostatisticians. This is especially troubling given that biostatisticians play a key role in the success or otherwise of clinical research conducted for evidence-based decisions. In this paper, we offer suggestions on how mentoring can be applied in practice to advance the statistical training of future biostatisticians. In particular, we propose steps that academic statistics departments, professional statistical societies, and statistics organizations can take to advance the mentoring of young biostatisticians. Our suggestions also cover what mentors and mentees can do to facilitate a successful mentoring relationship.Keywords: mentoring, biostatistics, career development

Lawrence Mbuagbaw1,2, Renée Cécile Bonono-Momnougui1, Lehana Thabane2,31Centre for the Development of Best Practices in Health (CDBPH), Yaoundé Central Hospital, Yaoundé, Cameroon; 2Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada; 3Biostatistics Unit, Father Sean O'Sullivan Research Centre, St Joseph's Healthcare, Hamilton, Ontario, CanadaAbstract: Poor adherence to highly active antiretroviral therapy (HAART) is a major hindrance to the reduction of mortality and morbidity due to HIV. This qualitative study used focus groups to explore the views and experiences of HIV patients on HAART with adherence reminders, especially the text message (SMS [short message service]). The ethnographic data obtained were used to design a clinical trial to assess the effect of motivational text messages versus usual care to enhance adherence to HAART among HIV patients in Yaoundé, Cameroon. Participants appreciated the idea of a timely SMS reminder, and cited the physician as a role model. They expressed concerns about privacy. Long-term life goals were a motivating factor to adhere. Overall, text messaging was viewed positively as a tool with a dual function of reminder and motivator. Messages coming from the attending physician may have a stronger impact. Trials investigating the use of text messages to improve adherence to HAART need to consider the content and timing of SMS, taking into account technical challenges and privacy.Keywords: focus groups, adherence, highly active antiretroviral therapy (HAART), text message, short message service (SMS), human immunodeficiency virus (HIV)