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1.  Determining Adverse Events in Patients with Neck Pain Receiving Orthopaedic Manual Physiotherapy: A Pilot and Feasibility Study 
Physiotherapy Canada  2013;65(3):255-265.
Purpose: To pilot and determine the feasibility of estimating adverse events in patients with neck pain treated with cervical manipulation/mobilization by Canadian orthopaedic manual physiotherapists (OMPTs) using an online data-collection system to provide estimates for a future larger multi-centre international study. Methods: In a prospective multi-site two-group cohort study, participants received usual care and either (a) combined manipulation and mobilization or (b) mobilization only. Study feasibility objectives and criteria for success were set a priori. Data were analyzed using descriptive statistics. Results: A total of 20 patients were recruited from 6 of 16 participating centres, 17 to the mobilization group and 3 to the combined group. Barriers to data collection included low recruitment, difficulties in using the online data-collection system, and clinicians' and patients' being too busy to participate. Missing data for the primary outcome averaged 28.5%. A total of 69 symptom occurrences were reported during the treatment phase, all benign and transient. Most began within 0–12 hours after treatment (66/69, 95.6%) and lasted for 0–2 days (56/69, 81.2%). Kappa estimates of agreement between therapists and patients on reporting of adverse symptoms across visits 1–5 was substantial (κ=0.68; 95% CI, 0.52–0.84; p<0.01). Conclusions: This pilot study demonstrates substantial challenges in conducting a large multi-centre trial. Brief, benign, and transient adverse events were common; no substantial adverse events were observed.
PMCID: PMC3740991  PMID: 24403696
adverse events; feasibility study; neck manipulation; pilot study; étude pilote; étude de faisabilité; événements indésirables; manipulation du cou; physiothérapie
2.  Frailty index of deficit accumulation and falls: data from the Global Longitudinal Study of Osteoporosis in Women (GLOW) Hamilton cohort 
To investigate the association between frailty index (FI) of deficit accumulation and risk of falls, fractures, death and overnight hospitalizations in women aged 55 years and older.
The data were from the Global Longitudinal Study of Osteoporosis in Women (GLOW) Hamilton Cohort. In this 3-year longitudinal, observational cohort study, women (N = 3,985) aged ≥55 years were enrolled between May 2008 and March 2009 in Hamilton, Canada. A FI including co-morbidities, activities of daily living, symptoms and signs, and healthcare utilization was constructed using 34 health deficits at baseline. Relationship between the FI and falls, fractures, death and overnight hospitalizations was examined.
The FI was significantly associated with age, with a mean rate of deficit accumulation across baseline age of 0.004 or 0.021 (on a log scale) per year. During the third year of follow-up, 1,068 (31.89%) women reported at least one fall. Each increment of 0.01 on the FI was associated with a significantly increased risk of falls during the third year of follow-up (odds ratio [OR]: 1.02, 95% confidence interval [CI]: 1.02-1.03). The area under the curve (AUC) of the predictive model was 0.69 (95% CI: 0.67-0.71). Results of subgroup and sensitivity analyses indicated the relationship between the FI and risk of falls was robust, while bootstrap analysis judged its internal validation. The FI was significantly related to fractures (hazard ratio [HR]: 1.02, 95% CI: 1.01-1.03), death (OR: 1.05, 95% CI: 1.03-1.06) during the 3-year follow-up period and overnight hospitalizations (incidence rate ratio [IRR]: 1.02, 95% CI: 1.02-1.03) for an increase of 0.01 on the FI during the third year of follow-up. Measured by per standard deviation (SD) increment of the FI, the ORs were 1.21 and 1.40 for falls and death respectively, while the HR was 1.17 for fractures and the IRR was 1.18 for overnight hospitalizations respectively.
The FI of deficit accumulation increased with chronological age significantly. The FI was associated with and predicted increased risk of falls, fractures, death and overnight hospitalizations significantly.
PMCID: PMC4046442  PMID: 24885323
Frailty; Falls; Fracture; Death; Hospitalization
3.  Sex differences in outcomes of methadone maintenance treatment for opioid addiction: a systematic review protocol 
Systematic Reviews  2014;3:45.
Use of methadone for the treatment of opioid addiction is an effective harm-reduction approach, although variability in treatment outcomes among individuals has been reported. Men and women with opioid addiction have been known to differ in factors such as opioid use patterns and characteristics at treatment entry; however, little has been reported about differences in methadone treatment outcomes between men and women. Therefore, we present a protocol for a systematic review which aims to provide a summary of existing literature on sex differences in outcomes of methadone treatment for opioid addiction.
Electronic search of PubMed/MEDLINE, EMBASE, PsycINFO, and CINAHL databases will be conducted using a priori defined search strategy. Two authors (MB and BBD) will independently screen potential articles for eligibility using pre-determined inclusion and exclusion criteria and extract key information using a data extraction form designed for this study. Discrepancies will be resolved using a third party (ZS). The primary outcome will be sex differences in response to treatment defined as abstinence from illicit opioid use. We will also assess sex differences in treatment outcomes including treatment retention, remission status post-treatment, polysubstance abuse, methadone dose, drug-related adverse events, health status, psychological status, mortality, criminal activity, high risk sexual behavior, social support/relations, and employment. A meta-analysis will be conducted if possible; risk of bias and overall quality of evidence will be assessed to determine confidence in the estimates.
We anticipate that this review will highlight how men and women differ in methadone treatment outcomes and allow us to generate conclusions that can be applied to treatment in a clinical setting.
Systematic review registration
PROSPERO CRD42013006549
PMCID: PMC4031161  PMID: 24887111
Opioid addiction/dependence; Methadone maintenance treatment; Sex differences; Systematic review; Protocol
4.  An interprofessional nurse-led mental health promotion intervention for older home care clients with depressive symptoms 
BMC Geriatrics  2014;14:62.
Depressive symptoms in older home care clients are common but poorly recognized and treated, resulting in adverse health outcomes, premature institutionalization, and costly use of health services. The objectives of this study were to examine the feasibility and acceptability of a new six-month interprofessional (IP) nurse-led mental health promotion intervention, and to explore its effects on reducing depressive symptoms in older home care clients (≥ 70 years) using personal support services.
A prospective one-group pre-test/post-test study design was used. The intervention was a six-month evidence-based depression care management strategy led by a registered nurse that used an IP approach. Of 142 eligible consenting participants, 98 (69%) completed the six-month and 87 (61%) completed the one-year follow-up. Outcomes included depressive symptoms, anxiety, health-related quality of life (HRQoL), and the costs of use of all types of health services at baseline and six-month and one-year follow-up. An interpretive descriptive design was used to explore clients’, nurses’, and personal support workers’ perceptions about the intervention’s appropriateness, benefits, and barriers and facilitators to implementation.
Of the 142 participants, 56% had clinically significant depressive symptoms, with 38% having moderate to severe symptoms. The intervention was feasible and acceptable to older home care clients with depressive symptoms. It was effective in reducing depressive symptoms and improving HRQoL at six-month follow-up, with small additional improvements six months after the intervention. The intervention also reduced anxiety at one year follow-up. Significant reductions were observed in the use of hospitalization, ambulance services, and emergency room visits over the study period.
Our findings provide initial evidence for the feasibility, acceptability, and sustained effects of the nurse-led mental health promotion intervention in improving client outcomes, reducing use of expensive health services, and improving clinical practice behaviours of home care providers. Future research should evaluate its efficacy using a randomized clinical trial design, in different settings, with an adequate sample of older home care recipients with depressive symptoms.
Trial registration identifier: NCT01407926.
PMCID: PMC4019952  PMID: 24886344
Nurse-led interventions; Home care; Interdisciplinary; Depression management; Older adults; Clinical effectiveness
5.  The Reporting of Observational Clinical Functional Magnetic Resonance Imaging Studies: A Systematic Review 
PLoS ONE  2014;9(4):e94412.
Complete reporting assists readers in confirming the methodological rigor and validity of findings and allows replication. The reporting quality of observational functional magnetic resonance imaging (fMRI) studies involving clinical participants is unclear.
We sought to determine the quality of reporting in observational fMRI studies involving clinical participants.
We searched OVID MEDLINE for fMRI studies in six leading journals between January 2010 and December 2011.Three independent reviewers abstracted data from articles using an 83-item checklist adapted from the guidelines proposed by Poldrack et al. (Neuroimage 2008; 40: 409–14). We calculated the percentage of articles reporting each item of the checklist and the percentage of reported items per article.
A random sample of 100 eligible articles was included in the study. Thirty-one items were reported by fewer than 50% of the articles and 13 items were reported by fewer than 20% of the articles. The median percentage of reported items per article was 51% (ranging from 30% to 78%). Although most articles reported statistical methods for within-subject modeling (92%) and for between-subject group modeling (97%), none of the articles reported observed effect sizes for any negative finding (0%). Few articles reported justifications for fixed-effect inferences used for group modeling (3%) and temporal autocorrelations used to account for within-subject variances and correlations (18%). Other under-reported areas included whether and how the task design was optimized for efficiency (22%) and distributions of inter-trial intervals (23%).
This study indicates that substantial improvement in the reporting of observational clinical fMRI studies is required. Poldrack et al.'s guidelines provide a means of improving overall reporting quality. Nonetheless, these guidelines are lengthy and may be at odds with strict word limits for publication; creation of a shortened-version of Poldrack's checklist that contains the most relevant items may be useful in this regard.
PMCID: PMC3995931  PMID: 24755843
6.  Effect of green tea supplementation on blood pressure among overweight and obese adults: a protocol for a systematic review 
BMJ Open  2014;4(4):e004971.
Emerging randomised controlled trials (RCTs) exploring the effect of green tea (GT) supplementation or GT extract (GTE) on blood pressure (BP) among overweight and obese adults yielded inconclusive results. We aim to conduct a systematic review to summarise the evidence of RCTs until now, to clarify the efficacy of GT supplementation or GTE in BP in overweight and obese populations.
Methods and analysis
The Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE and will be searched to retrieve potential RCTs. Unpublished studies will be identified by searching the abstract books or websites of the three major conference proceedings: the International Society of Hypertension, the Nutrition & Health Conference and the World Congress of Nutrition and Health. A random-effects meta-analysis will be performed to pool the mean difference for the change in BP from baseline (ie, postintervention BP minus baseline BP) between intervention groups and placebo groups of the included studies, presenting the pooled results with 95% CIs. Subgroups analyses will be conducted according to different doses of GT or GTE, trial duration, geographic regions, overweight versus obese participants, and participants with versus without change in body weight after intervention. Sensitivity analysis will be performed by excluding studies classified as having a high risk of bias, applying a fixed-effects model, using the postintervention BP for analyses and excluding trials with non-study cointerventions.
Ethics and dissemination
This systematic review will be published in a peer-reviewed journal. It will be disseminated electronically and in print. Summarising the RCT evidence to clarify the efficacy in BP among overweight and obese adults will aid in making the dietary recommendation of GT and improving the clinical management of hypertension.
Trial registration number
PROSPERO CRD42014007273.
PMCID: PMC3996813  PMID: 24742977
green tea; blood pressure; overweight; obese; systematic review protocol
7.  The effect of weekly text-message communication on treatment completion among patients with latent tuberculosis infection: study protocol for a randomised controlled trial (WelTel LTBI) 
BMJ Open  2014;4(4):e004362.
Interventions to improve adherence to treatment for latent tuberculosis infection (LTBI) are necessary to improve treatment completion rates and optimise tuberculosis (TB) control efforts. The high prevalence of cell phone use presents opportunities to develop innovative ways to engage patients in care. A randomised controlled trial (RCT), WelTel Kenya1, demonstrated that weekly text messages improved antiretroviral adherence and clinical outcomes among patients initiating HIV treatment. The aim of this study is to determine whether the WelTel intervention can improve treatment completion among patients with LTBI and to evaluate the intervention's cost-effectiveness.
Methods and analysis
This open, two-site, parallel RCT (WelTel LTBI) will be conducted at TB clinics in Vancouver and New Westminster, British Columbia, Canada. Over 2 years, we aim to recruit 350 individuals initiating a 9-month isoniazid regimen. Participants will be randomly allocated to an intervention or control (standard care) arm in a 1:1 ratio. Intervention arm participants will receive a weekly text-message ‘check-in’ to which they will be asked to respond within 48 h. A TB clinician will follow-up instances of non-response and problems that are identified. Participants will be followed until treatment completion (up to 12 months) or discontinuation. The primary outcome is self-reported treatment completion (taking ≥80% of doses within 12 months). Secondary outcomes include daily adherence (percentage of days participants used medication as prescribed) and time to treatment completion. Patient satisfaction with the intervention will be evaluated, and the intervention's cost-effectiveness will be analysed through decision-analytic modelling.
Ethics and dissemination
Ethical approval has been obtained from the University of British Columbia. This trial will test the efficacy and cost-effectiveness of the WelTel intervention to improve treatment completion among patients with LTBI. Trial results and economic evaluation will help inform policy and practice on the use of WelTel in this population.
Trial registration number NCT01549457.
PMCID: PMC3987735  PMID: 24719431
8.  Beliefs and Practice Patterns in Spinal Manipulation and Spinal Motion Palpation Reported by Canadian Manipulative Physiotherapists 
Physiotherapy Canada  2013;65(2):167-175.
Purpose: This practice survey describes how Fellows of the Canadian Academy of Manipulative Physiotherapy (FCAMPT) use spinal manipulation and mobilization and how they perceive their competence in performing spinal assessment; it also quantifies relationships between clinical experience and use of spinal manipulation. Methods: A cross-sectional survey was designed based on input from experts and the literature was administered to a random sample of the FCAMPT mailing list. Descriptive (including frequencies) and inferential statistical analyses (including linear regression) were performed. Results: The response rate was 82% (278/338 eligible FCAMPTs). Most (99%) used spinal manipulation. Two-thirds (62%) used clinical presentation as a factor when deciding to mobilize or manipulate. The least frequently manipulated spinal region was the cervical spine (2% of patients); 60% felt that cervical manipulation generated more adverse events. Increased experience was associated with increased use of upper cervical manipulation among male respondents (14% more often for every 10 years after certification; β, 95% CI=1.37, 0.89–1.85, p<0.001) but not among female respondents. Confidence in palpation accuracy decreased in lower regions of the spine. Conclusion: The use of spinal manipulation/mobilization is prevalent among FCAMPTs, but is less commonly used in the neck because of a perceived association with adverse events.
PMCID: PMC3673798  PMID: 24403681
beliefs; palpation; spinal manipulation; utilization; manipulation vertébrale; croyance; utilisation; précision
9.  Pharmacogenetic-Based Efavirenz Dose Modification: Suggestions for an African Population and the Different CYP2B6 Genotypes 
PLoS ONE  2014;9(1):e86919.
Pharmacogenetics contributes to inter-individual variability in pharmacokinetics (PK) of efavirenz (EFV), leading to variations in both efficacy and toxicity. The purpose of this study was to assess the effect of genetic factors on EFV pharmacokinetics, treatment outcomes and genotype based EFV dose recommendations for adult HIV-1 infected Ugandans.
In total, 556 steady-state plasma EFV concentrations from 99 HIV infected patients (64 female) treated with EFV/lamivudine/zidovidine were analyzed. Patient genotypes for CYP2B6 (*6 & *11), CYP3A5 (*3,*6 & *7) and ABCB1 c.4046A>G, baseline biochemistries and CD4 and viral load change from baseline were determined. A one-compartment population PK model with first-order absorption (NONMEM) was used to estimate genotype effects on EFV pharmacokinetics. PK simulations were performed based upon population genotype frequencies. Predicted AUCs were compared between the product label and simulations for doses of 300 mg, 450 mg, and 600 mg.
EFV apparent clearance (CL/F) was 2.2 and 1.74 fold higher in CYP2B6*6 (*1/*1) and CYP2B6*6 (*1/*6) compared CYP2B6*6 (*6/*6) carriers, while a 22% increase in F1 was observed for carriers of ABCB1 c.4046A>G variant allele. Higher mean AUC was attained in CYP2B6 *6/*6 genotypes compared to CYP2B6 *1/*1 (p<0.0001). Simulation based AUCs for 600 mg doses were 1.25 and 2.10 times the product label mean AUC for the Ugandan population in general and CYP2B6*6/*6 genotypes respectively. Simulated exposures for EFV daily doses of 300 mg and 450 mg are comparable to the product label. Viral load fell precipitously on treatment, with only six patients having HIV RNA >40 copies/mL after 84 days of treatment. No trend with exposure was noted for these six patients.
Results of this study suggest that daily doses of 450 mg and 300 mg might meet the EFV treatment needs of HIV-1 infected Ugandans in general and individuals homozygous for CYP2B6*6 mutation, respectively.
PMCID: PMC3909010  PMID: 24497997
10.  Impact of ABCB1 and CYP2B6 Genetic Polymorphisms on Methadone Metabolism, Dose and Treatment Response in Patients with Opioid Addiction: A Systematic Review and Meta-Analysis 
PLoS ONE  2014;9(1):e86114.
Genetic variability may influence methadone metabolism, dose requirements, and risk of relapse.
To determine whether the CYP2B6*6 or ABCB1 (rs1045642) polymorphisms are associated with variation in methadone response (plasma concentration, dose, or response to treatment).
Two independent reviewers searched Medline, EMBASE, CINAHL, PsycINFO, and Web of Science databases. We included studies that reported methadone plasma concentration, methadone response, or methadone dose in relation to the CYP2B6*6 or ABCB1 polymorphisms.
We screened 182 articles and extracted 7 articles for inclusion in the meta-analysis. Considerable agreement was observed between the two independent raters on the title (kappa, 0.82), abstract (kappa, 0.43), and full text screening (kappa, 0.43). Trough (R) methadone plasma concentration was significantly higher in CYP2B6*6 homozygous carriers when compared to non-carriers (standardized mean difference [SMD] = 0.53, 95% confidence interval [CI], 0.05–1.00, p = 0.03) with minimal heterogeneity (I2 = 0%). Similarly, trough (S) methadone plasma concentration was higher in homozygous carriers of the *6 haplotype when compared to non-carriers, (SMD = 1.44, 95% CI 0.27–2.61, p = 0.02) however significant heterogeneity was observed (I2 = 69%). Carriers of the CYP2B6*6 haplotype were not found to be significantly different from non-carriers with respect to dose or response to treatment. We found no significant association between the ABCB1 polymorphism and the trough (R), (S) plasma concentrations, methadone dose, or methadone response.
Although the number of studies included and sample size were modest, this is the first meta analysis to show participants homozygous for the CYP2B6*6 genotype have higher trough (R) and (S) methadone plasma concentrations, suggesting that methadone metabolism is significantly slower in *6 homozygous carriers.
PMCID: PMC3906028  PMID: 24489693
11.  Pulsed radiofrequency treatment of the lumbar dorsal root ganglion in patients with chronic lumbar radicular pain: a randomized, placebo-controlled pilot study 
Journal of Pain Research  2014;7:47-55.
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.
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.
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.
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.
PMCID: PMC3894138  PMID: 24453500
pulsed radiofrequency; radicular pain; dorsal root ganglion
12.  Patient-specific academic detailing for smoking cessation 
Canadian Family Physician  2014;60(1):e16-e23.
To describe and to determine the feasibility of a patient-specific academic detailing (PAD) smoking cessation (SC) program in a primary care setting.
Descriptive cohort feasibility study.
Hamilton, Ont.
Pharmacists, physicians, nurse practitioners, and their patients.
Integrated pharmacists received basic academic detailing training and education on SC and then delivered PAD to prescribers using structured verbal education and written materials. Data were collected using structured forms.
Main outcome measures
Five main feasibility criteria were generated based on Canadian academic detailing programs: PAD coordinator time to train pharmacists less than 40 hours; median time of SC education per pharmacist less than 20 hours; median time per PAD session less than 60 minutes for initial visit; percentage of prescribers receiving PAD within 3 months greater than 50%; and number of new SC referrals to pharmacists at 6 months more than 10 patients per 1.0 full-time equivalent (FTE) pharmacist (total of approximately 30 patients).
Eight pharmacists (5.8 FTE) received basic academic detailing training and education on SC PAD. Forty-eight physicians and 9 nurse practitioners consented to participate in the study. The mean PAD coordinator training time was 29.1 hours. The median time for SC education was 3.1 hours. The median times for PAD sessions were 15 and 25 minutes for an initial visit and follow-up visit, respectively. The numbers of prescribers who had received PAD at 3 and 6 months were 50 of 64 (78.1%) and 57 of 64 (89.1%), respectively. The numbers of new SC referrals at 3 and 6 months were 11 patients per FTE pharmacist (total of 66 patients) and 34 patients per FTE pharmacist (total of 200 patients), respectively.
This study met the predetermined feasibility criteria with respect to the management, resources, process, and scientific components. Further study is warranted to determine whether PAD is more effective than conventional academic detailing.
PMCID: PMC3994822  PMID: 24452574
13.  The impact of a cardiovascular health awareness program (CHAP) on reducing blood pressure: a prospective cohort study 
BMC Public Health  2013;13:1230.
Hypertension is an important and modifiable cardiovascular risk factor that remains under-detected and under-treated, especially in the older individuals. Community-led interventions that integrate primary health care and local resources are promising approaches to improve awareness and management of hypertension and other cardiovascular risk factors. We aimed to evaluate the effect of a community-based Cardiovascular Health Awareness Program (CHAP) on participants’ blood pressure.
This study followed a cohort of community residents that participated in CHAP across 22 mid-sized Ontario communities over an 18-month period. The participants’ baseline risk factors, including blood pressure, and subsequent measures of blood pressure were recorded. We employed a bivariate linear mixed-effect model to estimate the change of systolic and diastolic blood pressure over time among the participants who attended more than two CHAP sessions.
Of 13,596 participants, 2498 attended more than two CHAP sessions. For those repeated participants (attending more than two sessions) initially identified with high blood pressure, the average reduction of systolic blood pressure was from 142 to 123 mmHg over an 18-month period, a monthly rate ratio of 0.992 (95% CI: 0.991,0.994; p < 0.01). Similarly, the average reduction of diastolic blood pressure was from 78 to 69 mmHg, a monthly rate ratio of 0.993 (95% CI: 0.991,0.994; p < 0.01). The average blood pressure of the participants with normal baseline blood pressure remained controlled and unchanged. We also found that older adult participants who lived alone, were diagnosed with hypertension, reported healthier eating habits, and presented with a higher baseline systolic blood pressure had significantly greater odds of attending more than one session.
CHAP was associated with a reduction in systolic and diastolic blood pressure for those participants who attended more than one session. The magnitude of blood pressure reductions was significant clinically and statistically.
PMCID: PMC3883556  PMID: 24369050
14.  Effects of postnatal interventions for the reduction of vertical HIV transmission on infant growth and non-HIV infections: a systematic review 
Guidelines in resource-poor settings have progressively included interventions to reduce postnatal HIV transmission through breast milk. In addition to HIV-free survival, infant growth and non-HIV infections should be considered. Determining the effect of these interventions on infant growth and non-HIV infections will inform healthcare decisions about feeding HIV-exposed infants. We synthesize findings from studies comparing breast to formula feeding, early weaning to standard-duration breastfeeding, breastfeeding with extended antiretroviral (ARV) to short-course ARV prophylaxis, and alternative preparations of infant formula to standard formula in HIV-exposed infants, focusing on infant growth and non-HIV infectious morbidity outcomes. The review objectives were to collate and appraise evidence of interventions to reduce postnatal vertical HIV transmission, and to estimate their effect on growth and non-HIV infections from birth to two years of age among HIV-exposed infants.
We searched PubMed, SCOPUS, and Cochrane CENTRAL Controlled Trials Register. We included randomized trials and prospective cohort studies. Two authors independently extracted data and evaluated risk of bias. Rate ratios and mean differences were used as effect measures for dichotomous and continuous outcomes, respectively. Where pooling was possible, we used fixed-effects meta-analysis to pool results across studies. Quality of evidence was assessed using the GRADE approach.
Results and discussion
Prospective cohort studies comparing breast- versus formula-fed HIV-exposed infants found breastfeeding to be protective against diarrhoea in early life [risk ratio (RR)=0.31; 95% confidence interval (CI)=0.13 to 0.74]. The effect of breastfeeding against diarrhoea [hazard ratio (HR)=0.74; 95% CI=0.57 to 0.97] and respiratory infections (HR=0.65; 95% CI=0.41 to 1.00) was significant through two years of age. The only randomized controlled trial (RCT) available showed that breastfeeding tended to be protective against malnutrition (RR=0.63; 95% CI=0.36 to 1.12). We found no statistically significant differences in the rates of non-HIV infections or malnutrition between breast-fed infants in the extended and short-course ARV prophylaxis groups.
Low to moderate quality evidence suggests breastfeeding may improve growth and non-HIV infection outcomes of HIV-exposed infants. Extended ARV prophylaxis does not appear to increase the risk for HIV-exposed infants for adverse growth or non-HIV infections compared to short-course ARV prophylaxis.
PMCID: PMC3871831  PMID: 24369738
postnatal interventions; HIV; children; growth; non-HIV infections; breast milk
15.  Mobile phone text messages for improving adherence to antiretroviral therapy (ART): an individual patient data meta-analysis of randomised trials 
BMJ Open  2013;3(12):e003950.
Our objectives were to analyse the effects of text messaging versus usual care in improving adherence to antiretroviral therapy (ART) in people living with HIV using individual patient data meta-analysis. Adjusted, sensitivity and subgroup analyses were conducted.
3 randomised controlled trials conducted between 2010 and 2012 in rural and urban centres in Cameroon and Kenya (two studies) were used.
A total of 1166 participants were included in this analysis (Cameroon=200; Kenya=428 and 538).
Primary and secondary outcomes
The primary outcome was adherence to ART >95%. The secondary outcomes were mortality, losses to follow-up, transfers and withdrawals.
Text messaging improved adherence to ART (OR 1.38; 95% CIs 1.08 to 1.78; p=0.012), even after adjustment for baseline covariates (OR 1.46; 95% CI 1.13 to 1.88; p=0.004). Primary education (compared with no formal education) was associated with a greater intervention effect on adherence (OR 1.65; 95% CI 1.10 to 2.48; p=0.016) and also showed a significant subgroup effect (p=0.039). In sensitivity analysis, our findings were robust to a modified threshold of adherence, multiple imputation for missing data and aggregate level data pooling, but not to fixed-effects meta-analyses using generalised estimation equations. There was a significant subgroup effect for long weekly (p=0.037), short weekly text messages (p=0.014) and interactive messaging (p=0.010). Text messaging did not significantly affect any of the secondary outcomes.
Text messaging has a significant effect on adherence to ART, and this effect is influenced by level of education, gender, timing (weekly vs daily) and interactivity. We recommend the use of interactive weekly text messaging to improve adherence to ART, which is most effective in those with at least a primary level of education.
PMCID: PMC3884740  PMID: 24345901
16.  Preferences for Evidence–Based Practice Dissemination in Addiction Agencies Serving Women: A Discrete–Choice Conjoint Experiment 
Addiction (Abingdon, England)  2012;107(8):10.1111/j.1360-0443.2012.03832.x.
To model variables influencing the dissemination of evidence-based practices to addiction service providers and administrators.
A discrete–choice conjoint experiment. We systematically varied combinations of 16 dissemination variables that might influence the adoption of evidence-based practices. Participants chose between sets of variables.
Canadian agencies (n=333) providing addiction services to women.
Service providers and administrators (n=1379).
We estimated the relative importance and optimal level of each dissemination variable. We used Latent Class analysis to identify subsets of participants with different preferences and simulated the conditions under which participants would use more demanding professional development options..
Three subsets of participants were identified: outcome sensitive (52%), process sensitive (29.6%) and demand sensitive (18.2%). Across all participants, the number of clients who were expected to benefit from an evidence-based practice exerted the most influence on dissemination choices. If a practice was seen as feasible, co-worker and administrative support influenced decisions. Client benefits were most important to outcome-sensitive participants; type of dissemination process (e.g. active versus passive learning) was more important to process-sensitive participants. Brief options with little follow-up were preferred by demand-sensitive participants. Simulations predicted that initiatives selected and endorsed by government funders would reduce participation.
Clinicians and administrators are more likely to adopt evidence-based addiction practices if the practice is seen as helpful to clients, and if it is supported by co-workers and program administration.
PMCID: PMC3864861  PMID: 22296280 CAMSID: cams3708
addiction; conjoint analysis; discrete choice conjoint experiment; dissemination; implementation; reactance
17.  Uptake of an innovation in surgery: observations from the cluster-randomized Quality Initiative in Rectal Cancer trial 
Canadian Journal of Surgery  2013;56(6):415-421.
Theory suggests the uptake of a medical innovation is influenced by how potential adopters perceive innovation characteristics and by characteristics of potential adopters. Innovation adoption is slow among the first 20% of individuals in a target group and then accelerates. The Quality Initiative in Rectal Cancer (QIRC) trial assessed if rectal cancer surgery outcomes could be improved through surgeon participation in the QIRC strategy. We tested if traditional uptake of innovation concepts applied to surgeons in the experimental arm of the trial.
The QIRC strategy included workshops, access to opinion leaders, intra-operative demonstrations, postoperative questionnaires, and audit and feedback. For intraoperative demonstrations, a participating surgeon invited an outside surgeon to demonstrate optimal rectal surgery techniques. We used surgeon timing in a demonstration to differentiate early and late adopters of the QIRC strategy. Surgeons completed surveys on perceptions of the strategy and personal characteristics.
Nineteen of 56 surgeons (34%) requested an operative demonstration on their first case of rectal surgery. Early and late adopters had similar perceptions of the QIRC strategy and similar characteristics. Late adopters were less likely than early adopters to perceive an advantage for the surgical techniques promoted by the trial (p = 0.023).
Most traditional diffusion of innovation concepts did not apply to surgeons in the QIRC trial, with the exception of the importance of perceptions of comparative advantage.
PMCID: PMC3859785  PMID: 24284150
18.  Patterns of use and outcomes for radiation therapy in the Quality Initiative in Rectal Cancer (QIRC) trial 
Canadian Journal of Surgery  2013;56(6):E148-E153.
The Quality Initiative in Rectal Cancer (QIRC) trial targeted surgeon intraoperative technique and not radiation therapy (RT) use. We performed a post hoc analysis of RT use among patients in the QIRC trial, not by arm of trial but rather for the entire group. We wished to identify associations between local recurrence risk and use of preoperative, postoperative or no RT
We compared demographic, tumour and process of care measures among patients receiving preoperative, postoperative or no RT. A multivariable Cox regression model assessed local recurrence risk.
The QIRC trial enrolled 1015 patients at 16 hospitals between 2002 and 2004. Radiation therapy use did not differ between trial arms, and median follow-up was 3.6 years. For the preoperative, postoperative and no RT groups, respectively, the percentage of patients was 12.8%, 19.3% and 67.9%; the percentage of stage II/III tumours was 57.0%, 88.7% and 48.1%; and the local recurrence rate was 5.3%, 10.2% and 5.5% (p = 0.05). After controlling for patient and tumour characteristics, including tumour stage, the hazard ratio (HR) for local recurrence was increased in the postoperative RT versus the no RT group (HR 1.64, 95% confidence interval 1.04–2.58, p = 0.027).
Use of preoperative RT was low; most patients with stage II/III disease did not receive RT and, as expected, the postoperative RT group had the highest risk of local recurrence. Our results suggest opportunities to improve rectal cancer RT use in Ontario.
PMCID: PMC3859789  PMID: 24284154
20.  Randomized controlled trials in pediatric critical care: a scoping review 
Critical Care  2013;17(5):R256.
Evidence from randomized controlled trials (RCTs) is required to guide treatment of critically ill children, but the number of RCTs available is limited and the publications are often difficult to find. The objectives of this review were to systematically identify RCTs in pediatric critical care and describe their methods and reporting.
We searched MEDLINE, EMBASE, LILACS and CENTRAL (from inception to April 16, 2013) and reference lists of included RCTs and relevant systematic reviews. We included published RCTs administering any intervention to children in a pediatric ICU. We excluded trials conducted in neonatal ICUs, those enrolling exclusively preterm infants, and individual patient crossover trials. Pairs of reviewers independently screened studies for eligibility, assessed risk of bias, and abstracted data. Discrepancies were resolved by consensus.
We included 248 RCTs: 45 (18%) were multicentered and 14 (6%) were multinational. Trials most frequently enrolled both medical and surgical patients (43%) but postoperative cardiac surgery was the single largest population studied (19%). The most frequently evaluated types of intervention were medications (63%), devices (11%) and nutrition (8%). Laboratory or physiological measurements were the most frequent type of primary outcomes (18%). Half of these trials (50%) reported blinding. Of the 107 (43%) trials that reported an a priori sample size, 34 (32%) were stopped early. The median number of children randomized per trial was 49 and ranged from 6 to 4,947. The frequency of RCT publications increased at a mean rate of 0.7 RCTs per year (P<0.001) from 1 to 20 trials per year.
This scoping review identified the available RCTs in pediatric critical care and made them accessible to clinicians and researchers ( Most focused on medications and intermediate or surrogate outcomes, were single-centered and were conducted in North America and Western Europe. The results of this review underscore the need for trials with rigorous methodology, appropriate outcome measures, and improved quality of reporting to ensure that high quality evidence exists to support clinical decision-making in this vulnerable population.
PMCID: PMC4057256  PMID: 24168782
21.  Development and feasibility testing of decision support for patients who are candidates for a prophylactic implantable defibrillator: a study protocol for a pilot randomized controlled trial 
Trials  2013;14:346.
Patients, identified to be at risk for but who have never experienced a potentially lethal cardiac arrhythmia, have the option of receiving an implantable cardioverter defibrillator (ICD) as prophylaxis against sudden cardiac death - a primary prevention indication. In Canada, there is no clear framework to support patients’ decision-making for these devices. Decision support, using a decision aid, could moderate treatment-related uncertainty and prepare patients to make well-informed decisions. Patient decision aids provide information on treatment options, risks, and benefits, to help patients clarify their values for outcomes of treatment options. The objectives of this research are: 1) develop a decision aid, 2) evaluate the decision aid, and 3) determine the feasibility of conducting a trial.
A development panel comprised of the core investigative team, health service researchers, decision science experts, cardiovascular healthcare practitioners, and ICD patient representatives will collaborate to provide input on the content and format of the aid. To generate probabilities to include in the aid, we will synthesize primary prevention ICD evidence. To obtain anonymous input about the facts and content, we will employ a modified Delphi process. To evaluate the draft decision aid will invite ICD patients and their families (n = 30) to rate its acceptability. After we evaluate the aid, to determine the feasibility, we will conduct a feasibility pilot randomized controlled trial (RCT) in new ICD candidates (n = 80). Participants will be randomized to receive a decision aid prior to specialist consultation versus usual care. Results from the pilot RCT will determine the feasibility of research processes; inform sample size calculation, measure decision quality (knowledge, values, decision conflict) and the influence of health related quality of life on decision-making.
Our study seeks to develop a decision aid, for patients offered their first ICD for prophylaxis against sudden cardiac death. This paper outlines the background and methods of a pilot randomized trial which will inform a larger multicenter trial. Ultimately, decision support prior to specialist consultation could enhance the decision-making process between patients, physicians, and families, associated with life-prolonging medical devices like the ICD.
Trial registration NCT01876173
PMCID: PMC4015905  PMID: 24148851
Decision aid; Feasibility trial; Implantable defibrillator; Decision-making; Shared decision-making
22.  The effects of rituximab on serum IgE and BAFF 
There are few treatment options for patients with severe atopic asthma. Antagonism of IgE is an effective strategy. We investigated, by utilizing serum samples from a clinical trial of Rituximab in patients with Idiopathic Thrombocytopenic Purpura, if B cell depletion would decrease serum IgE and therefore be a potential therapeutic option.
In a placebo-controlled randomized clinical trial of Rituximab, an anti-CD20 molecule, there were no significant differences in serum levels of IgE or BAFF levels between the two treatment groups at 3 or 6 months irrespective of the baseline serum IgE levels.
Since Rituximab did not significantly decrease serum IgE levels, this proof of concept study suggests that Rituximab may not be a useful treatment strategy for patients with severe IgE mediated disease.
PMCID: PMC3850905  PMID: 24219860
Anti-CD20; Rituximab; Immunoglobulin E; BAFF; Asthma
23.  A sensitivity analysis of the Children’s Treatment Network trial: a randomized controlled trial of integrated services versus usual care for children with special health care needs 
Clinical Epidemiology  2013;5:373-385.
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.
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.
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.
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.
PMCID: PMC3789843  PMID: 24098089
children with special health care needs; chronically ill; family-centered care; randomized controlled trial; noncompliance
24.  HIV prevention in favour of the choice-disabled in southern Africa: study protocol for a randomised controlled trial 
Trials  2013;14:274.
Most HIV prevention strategies assume beneficiaries can act on their prevention decisions. But some people are unable to do so. They are ‘choice-disabled’. Economic and educational interventions can reduce sexual violence, but there is less evidence that they can reduce HIV. There is little research on complex interventions in HIV prevention, yet all countries in southern Africa implement combination prevention programmes.
The primary objective is to reduce HIV infections among women aged 15 to 29 years. Secondary objectives are reduction in gender violence and improvement in HIV-related knowledge, attitudes and practices among youth aged 15 to 29 years.
A random sample of 77 census enumeration areas in three countries (Botswana, Namibia and Swaziland) was allocated randomly to three interventions, alone or in combination, in a factorial design stratified by country, HIV rates (above or below average for country), and urban/rural location. A baseline survey of youth aged 15 to 29 years provided cluster specific rates of HIV. All clusters continue existing prevention efforts and have a baseline and follow-up survey. Cluster is the unit of allocation, intervention and analysis, using generalised estimating equations, on an intention-to-treat basis.
One intervention discusses evidence about choice disability with local HIV prevention services, to help them to serve the choice-disabled. Another discusses an eight-episode audio-docudrama with community groups, of all ages and both sexes, to generate endogenous strategies to reduce gender violence and develop an enabling environment. A third supports groups of women aged 18 to 25 years to build self-esteem and life skills and to set up small enterprises to generate income.
A survey in all clusters after 3 years will measure outcomes, with interviewers unaware of group assignment of the clusters. The primary outcome is HIV infection in women aged 15 to 29 years. Secondary outcomes in youth aged 15 to 29 years are gender violence and protective knowledge, attitudes, subjective norms, intention to change, agency, discussion of prevention and practices related to HIV and gender violence.
Trial registration
Trial registration number: ISRCTN28557578
PMCID: PMC3765989  PMID: 23987126
HIV prevention; Gender violence; Southern Africa; Cluster randomised controlled trial
25.  The effect of regular physical activity on bone mineral density in post-menopausal women aged 75 and over: a retrospective analysis from the Canadian multicentre osteoporosis study 
Physical activity is known to benefit many physiological processes, including bone turnover. There are; however, currently no clinical guidelines regarding the most appropriate type, intensity and duration of activity to prevent bone loss.
To help address this gap in the literature, we performed a retrospective analysis of data from the Canadian Multicentre Osteoporosis Study (CaMos), a prospective cohort of 9423 adult patients, to determine the relationship between the amount of regular daily physical activity performed and bone mineral density. A total of 1169 female participants aged 75 and over provided information regarding their daily activity levels, including the amount of time spent each week performing physical activity at varying levels of intensity. Multiple and linear regression analyses were used to determine the effect of increasing amounts of this regular physical activity on bone mineral density.
The results indicate that a step increase in the amount of physical activity performed each day resulted in a positive effect on bone mineral density at the hip, Ward’s triangle, trochanter and femoral neck (B = 0.006 to 0.008, p < 0.05). Possible confounding factors such as the use of anti-resorptive therapy, body mass index and age were included in the analysis and suggested that age had a negative effect on bone density while body mass index had a positive effect. Anti-resorptive therapy provided a protective effect against loss of bone density.
The data indicate that a step increase in the amount of daily activity, using simple, daily performed tasks, can help prevent decreases in post-menopausal bone mineral density.
PMCID: PMC3765292  PMID: 23971674
Osteoporosis; Physical activity; Bone mineral density; Post-menopausal

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