Sunita Vohra’s research while affiliated with University of Alberta and other places

Background Trial registration aims to address potential bias from selective or non-reporting of findings, and therefore has a vital role in promoting transparency and accountability of clinical research. In this study, we aim to investigate the influence of trial registration on estimated harm effects in randomized controlled trials of medication interventions. Methods We searched PubMed for systematic reviews and meta-analyses of randomized trials on medication harms indexed between January 1, 2015, and January 1, 2020. To be included in the analyses, eligible meta-analyses should have at least five randomized trials with distinct registration statuses (i.e., prospectively registered, retrospectively registered, and non-registered) and 2 by 2 table data for adverse events for each trial. To control for potential confounding, trials in each meta-analysis were analyzed within confounder-harmonized groups (e.g., dosage) identified using the Directed Acyclic Graph method. The harm estimates arising from the trials with different registration statuses were compared within the confounder-harmonized groups using hierarchical linear regression. Results are shown as ratio of odds ratio (OR) and 95% confidence interval (CI). Results The dataset consists of 629 meta-analyses of harms with 10,069 trials. Of these trials, 74.3% were registered, and 23.9% were not registered, and for those registered, 70.6% were prospectively registered, while 26.3% were retrospectively registered. In comparison to prospectively registered trials, both non-registered trials (ratio of OR = 0.82, 95%CI 0.68 to 0.98, P = 0.03) and retrospectively registered trials (ratio of OR = 0.75, 95%CI 0.66 to 0.86, P < 0.01) had lower OR for harms based on 69 and 126 confounders-harmonized groups. The OR of harms did not differ between retrospectively registered and non-registered trials (ratio of OR = 1.02, 95%CI 0.85 to 1.23, P = 0.83) based on 76 confounders-harmonized groups. Conclusions Medication-related harms may be understated in non-registered trials, and there was no obvious evidence that retrospective registration had a demonstrable benefit in reducing such selective or absent reporting. Prospective registration is highly recommended for future trials.

BACKGROUND: Heat loss in the delivery room in very preterm infants is associated with increased mortality, hypothermia and other adverse outcomes. The Heat Loss Preventions (HeLP) trial was designed to address these outcomes and resulted in a significant reduction of hypothermia but not a reduction in mortality. The HeLP follow-up trial was designed to determine whether application of occlusive wrap applied immediately after birth reduces adverse long-term neurodevelopmental outcomes at 18-24 months corrected gestational age in very preterm infants. STUDY DESIGN: The original HeLP trial was a randomized controlled trial of very preterm infants (< 28 weeks gestation) placed at birth in occlusive wrap (wrap group) or not placed in occlusive wrap (control group). The HeLP follow-up trial was the later assessment of these infants enrolled in the HeLP trial to determine the composite outcome of death or neurodevelopmental disability at 18-24 month corrected gestational age. RESULTS: There were 356 infants eligible for follow-up from the randomized controlled HeLP trial with a loss to follow-up of 116/356 (32.6%). The primary outcome occurred in 82/113 in the wrap group and 80/127 in the control group (p=0.149, Fisher’s exact). Because of the large loss to follow-up rate, this unadjusted odds ratio was 1.55 (95% confidence interval=0.90-2.69) while the adjusted odds ratio (adjusted for major predictors of the outcome) was virtually unchanged at 1.52 (95% confidence interval=0.83-2.80). Secondary outcomes in the wrap versus control group were: cerebral palsy 9/70 versus 5/87 (p=0.204, Fisher’s exact), Mental Developmental Index (MDI) < 85 (Bayley Scales) 30/53 versus 33/67 (p=0.538, Fisher’s exact), blindness at 0/68 versus 1/86 (p>0.999, Fisher’s exact) and deafness 5/70 versus 6/87 (p>0.999, Fisher’s exact). No difference was noted in prescription glasses, 7/70 in the wrap group versus 2/87 in the control group (p=0.085, Fisher’s exact). CONCLUSION: Use of polyethylene occlusive wrap after birth in very preterm infants was associated with similar death or long-term neurodevelopmental disability rate. Clinical Trials Registry: Clinicaltrials.gov NCT00607464

This prospective, community-based, active surveillance study aimed to report the incidence of moderate, severe, and serious adverse events (AEs) after chiropractic (n = 100) / physiotherapist (n = 50) visit in offices throughout North America between October-2015 and December-2017. Three content-validated questionnaires were used to collect AE information: two completed by the patient (pre-treatment [T0] and 2–7 days post-treatment [T2]) and one completed by the provider immediately post-treatment [T1]. Any new or worsened symptom was considered an AE and further classified as mild, moderate, severe or serious. From the 42 participating providers (31 chiropractors; 11 physiotherapists), 3819 patient visits had complete T0 and T1 assessments. The patients were on average 50±18 years of age and 62.5% females. Neck/back pain was the most common presenting condition (70.0%) with 24.3% of patients reporting no condition/preventative care. From the patients visits with a complete T2 assessment (n = 2136 patient visits, 55.9%), 21.3% reported an AE, of which: 7.9% were mild, 6.2% moderate, 3.7% severe, 1.5% serious, and 2.0% had missing severity rating. The most common symptoms reported with moderate or higher severity were discomfort/pain, stiffness, difficulty walking and headache. This study provides valuable information for patients and providers regarding incidence and severity of AEs following patient visits in multiple community-based professions. These findings can be used to inform patients of what AEs may occur and future research opportunities can focus on mitigating common AEs.

Background Empirical evidence suggests that lack of blinding may be associated with biased estimates of treatment benefit in randomized controlled trials, but the influence on medication-related harms is not well-recognized. We aimed to investigate the association between blinding and clinical trial estimates of medication-related harms. Methods We searched PubMed from January 1, 2015, till January 1, 2020, for systematic reviews with meta-analyses of medication-related harms. Eligible meta-analyses must have contained trials both with and without blinding. Potential covariates that may confound effect estimates were addressed by restricting trials within the comparison or by hierarchical analysis of harmonized groups of meta-analyses (therefore harmonizing drug type, control, dosage, and registration status) across eligible meta-analyses. The weighted hierarchical linear regression was then used to estimate the differences in harm estimates (odds ratio, OR) between trials that lacked blinding and those that were blinded. The results were reported as the ratio of OR (ROR) with its 95% confidence interval (CI). Results We identified 629 meta-analyses of harms with 10,069 trials. We estimated a weighted average ROR of 0.68 (95% CI: 0.53 to 0.88, P < 0.01) among 82 trials in 20 meta-analyses where blinding of participants was lacking. With regard to lack of blinding of healthcare providers or outcomes assessors, the RORs were 0.68 (95% CI: 0.53 to 0.87, P < 0.01 from 81 trials in 22 meta-analyses) and 1.00 (95% CI: 0.94 to 1.07, P = 0.94 from 858 trials among 155 meta-analyses) respectively. Sensitivity analyses indicate that these findings are applicable to both objective and subjective outcomes. Conclusions Lack of blinding of participants and health care providers in randomized controlled trials may underestimate medication-related harms. Adequate blinding in randomized trials, when feasible, may help safeguard against potential bias in estimating the effects of harms.

Complementary therapies are commonly used to prevent and treat various medical conditions worldwide. The chapter begins with a description of the epidemiology of complementary therapies use among individuals with renal conditions, and discusses the legal and ethical considerations of complementary therapy use. This is followed by a review of the scientific evidence regarding the efficacy and safety of complementary therapies (including natural health products, traditional Chinese medicine and massage) used to prevent and treat symptoms associated with various renal conditions (including urinary tract infections, nephrotic syndrome, and chronic kidney disease) with a special focus on pediatric populations. Some complementary therapies considered (e.g. cranberry, and omega-3 fatty acids) have been researched more widely among pediatric populations than others; pediatric data are preferentially discussed when available. Some complementary therapies may be effective and relatively safe for use among pediatric populations (e.g. acupressure or acupuncture for uremic pruritus), while other complementary therapies have limited evidence and warrant further investigation (e.g. many traditional Chinese medicine herbal remedies).KeywordsComplementary therapiesComplementary treatmentsComplementary and alternative medicineRenal diseasePediatricNatural health productsTraditional Chinese medicineComplementary medicine safety

Randomized controlled trials remain the reference standard for healthcare research on effects of interventions, and the need to report both benefits and harms is essential. The Consolidated Standards of Reporting Trials (the main CONSORT) statement includes one item on reporting harms (i.e., all important harms or unintended effects in each group). In 2004, the CONSORT group developed the CONSORT Harms extension; however, it has not been consistently applied and needs to be updated. Here, we describe CONSORT Harms 2022, which replaces the CONSORT Harms 2004 checklist, and shows how CONSORT Harms 2022 items could be incorporated into the main CONSORT checklist. Thirteen items from the main CONSORT were modified to improve harms reporting. Three new items were added. In this article, we describe CONSORT Harms 2022 and how it was integrated into the main CONSORT checklist and elaborate on each item relevant to complete reporting of harms in randomized controlled trials. Until future work from the CONSORT group produces an updated checklist, authors, journal reviewers, and editors of randomized controlled trials should use the integrated checklist presented in this paper.

Objectives: In evidence synthesis practice, dealing with studies with no cases in both arms has been a tough problem, for which there is no consensus in the research community. In this study, we propose a method to measure the potential impact of studies with no cases for meta-analysis results which we define as harms index (Hi) and benefits index (Bi) as an alternative solution for deciding how to deal with such studies. Methods: Hi and Bi are defined by the minimal number of cases added to the treatment arm (Hi) or control arm (Bi) of studies with no cases in a meta-analysis that lead to a change of the direction of the estimates or its statistical significance. Both exact and approximating methods are available to calculate Hi and Bi. We developed the "hibi" module in Stata so that researchers can easily implement the method. A real-world investigation of meta-analyses from Cochrane reviews was employed to evaluate the proposed method. Results: Based on Hi and Bi, our results suggested that 21.53% (Hi) to 26.55% (Bi) of Cochrane meta-analyses may be potentially impacted by studies with no cases, for which studies with no cases could not be excluded from the synthesis. The approximating method shows excellent specificity (100%) for both Hi and Bi, moderate sensitivity (68.25%) for Bi, and high sensitivity (80.61%) for Hi compared to the exact method. Conclusions: The proposed method is practical and useful for systematic reviewers to measure whether studies with no cases impact the results of meta-analyses and may act as an alternative solution for review authors to decide whether to include studies with no events for the synthesis or not.

Aim: Opioid use disorder (OUD) is a leading cause of preventable mortality amongst young people worldwide. Early identification and intervention of modifiable risk factors may reduce future OUD risk. The aim of this study was to explore whether the onset of OUD is associated with preexisting mental health conditions such as anxiety and depressive disorders in young people. Methods: A retrospective, population-based case-control study was conducted from 31 March 2018 until 01 January 2002. Provincial administrative health data were collected from Alberta, Canada. Cases: Individuals 18-25 years on 01 April 2018, with a previous record of OUD. Controls: Individuals without OUD were matched to cases, on age/sex/index date. Conditional logistic regression analysis was used to control for additional covariates (e.g., alcohol-related disorders, psychotropic medications, opioid analgesics, and social/material deprivation). Results: We identified N = 1848 cases and N = 7392 matched controls. After adjustment, OUD was associated with the following preexisting mental health conditions: Anxiety disorders, aOR = 2.53 (95% CI = 2.16-2.96); depressive disorders, aOR = 2.20 (95% CI = 1.80-2.70); alcohol-related disorders, aOR = 6.08 (95% CI, 4.86-7.61); anxiety and depressive disorders, aOR = 1.94 (95% CI = 1.56-2.40); anxiety and alcohol-related disorders, aOR = 5.22 (95% CI = 4.03-6.77); depressive and alcohol-related disorders, aOR = 6.47 (95% CI = 4.73-8.84); anxiety, depressive and alcohol-related disorders, aOR = 6.09 (95% CI = 4.41-8.42). Discussion: Preexisting mental health conditions such as anxiety and depressive disorders are risk factors for future OUD in young people. Preexisting alcohol-related disorders showed the strongest association with future OUD and demonstrated an additive risk when concurrent with anxiety/depression. As not all plausible risk factors could be examined, more research is still needed.