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1.
J Clin Epidemiol ; 143: 149-158, 2021 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-34896234

RESUMO

OBJECTIVES: To describe prevalence of multiple primary outcomes, changes in primary outcomes and target sample sizes between protocols and final reports, and how issues of multiplicity are addressed in pragmatic trials. STUDY DESIGN AND SETTING: Individually randomized trials labeled as pragmatic, published 2014-2019 in MEDLINE and registered with ClinicalTrials.gov. RESULTS: We identified 262 final reports and located protocols for 159 (61%); primary outcomes were clearly reported in 145 (91%) protocols and 256 (98%) final reports. Thirty (19%) protocols and 38 (15%) final reports had multiple primary outcomes. Primary outcomes were present and identical in 128 (81%) matched protocol-final reports. Among 140 pairs with target sample sizes reported, 28 (20.0%) reduced their target sample size (mean 543 fewer participants per trial) and 16 (11.4%) increased it (mean 192 more participants per trial). Thirteen (29.5%) provided an explanation. Only 2 of 30 (7%) protocols and 4 of 38 (11%) final reports with co-primary outcomes explained how results would be interpreted in light of multiplicity; 21 of 30 (70%) protocols and 20 of 38 (53%) final reports accounted for co-primary outcomes in power calculations. CONCLUSION: Co-primary outcomes are common in pragmatic trials; improved transparency around design and analysis decisions involving co-primary outcomes is required.

2.
Clin Trials ; : 17407745211046672, 2021 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-34841910

RESUMO

BACKGROUND AND AIMS: We need more pragmatic trials of interventions to improve care and outcomes for people living with Alzheimer's disease and related dementias. However, these trials present unique methodological challenges in their design, analysis, and reporting-often, due to the presence of one or more sources of clustering. Failure to account for clustering in the design and analysis can lead to increased risks of Type I and Type II errors. We conducted a review to describe key methodological characteristics and obtain a "baseline assessment" of methodological quality of pragmatic trials in dementia research, with a view to developing new methods and practical guidance to support investigators and methodologists conducting pragmatic trials in this field. METHODS: We used a published search filter in MEDLINE to identify trials more likely to be pragmatic and identified a subset that focused on people living with Alzheimer's disease or other dementias or included them as a defined subgroup. Pairs of reviewers extracted descriptive information and key methodological quality indicators from each trial. RESULTS: We identified N = 62 eligible primary trial reports published across 36 different journals. There were 15 (24%) individually randomized, 38 (61%) cluster randomized, and 9 (15%) individually randomized group treatment designs; 54 (87%) trials used repeated measures on the same individual and/or cluster over time and 17 (27%) had a multivariate primary outcome (e.g. due to measuring an outcome on both the patient and their caregiver). Of the 38 cluster randomized trials, 16 (42%) did not report sample size calculations accounting for the intracluster correlation and 13 (34%) did not account for intracluster correlation in the analysis. Of the 9 individually randomized group treatment trials, 6 (67%) did not report sample size calculations accounting for intracluster correlation and 8 (89%) did not account for it in the analysis. Of the 54 trials with repeated measurements, 45 (83%) did not report sample size calculations accounting for repeated measurements and 19 (35%) did not utilize at least some of the repeated measures in the analysis. No trials accounted for the multivariate nature of their primary outcomes in sample size calculation; only one did so in the analysis. CONCLUSION: There is a need and opportunity to improve the design, analysis, and reporting of pragmatic trials in dementia research. Investigators should pay attention to the potential presence of one or more sources of clustering. While methods for longitudinal and cluster randomized trials are well developed, accessible resources and new methods for dealing with multiple sources of clustering are required. Involvement of a statistician with expertise in longitudinal and clustered designs is recommended.

3.
Emerg Med J ; 2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-34740890

RESUMO

BACKGROUND: Published risk tools do not provide possible management options for syncope in the emergency department (ED). Using the 30-day observed risk estimates based on the Canadian Syncope Risk Score (CSRS), we developed personalised risk prediction to guide management decisions. METHODS: We pooled previously reported data from two large cohort studies, the CSRS derivation and validation cohorts, that prospectively enrolled adults (≥16 years) with syncope at 11 Canadian EDs between 2010 and 2018. Using this larger cohort, we calculated the CSRS calibration and discrimination, and determined with greater precision than in previous studies the 30-day risk of adjudicated serious outcomes not identified during the index ED evaluation depending on the CSRS and the risk category. Based on these findings, we developed an on-line calculator and pictorial decision aids. RESULTS: 8233 patients were included of whom 295 (3.6%, 95% CI 3.2% to 4.0%) experienced 30-day serious outcomes. The calibration slope was 1.0, and the area under the curve was 0.88 (95% CI 0.87 to 0.91). The observed risk increased from 0.3% (95% CI 0.2% to 0.5%) in the very-low-risk group (CSRS -3 to -2) to 42.7% (95% CI 35.0% to 50.7%), in the very-high-risk (CSRS≥+6) group (Cochrane-Armitage trend test p<0.001). Among the very-low and low-risk patients (score -3 to 0), ≤1.0% had any serious outcome, there was one death due to sepsis and none suffered a ventricular arrhythmia. Among the medium-risk patients (score +1 to+3), 7.8% had serious outcomes, with <1% death, and a serious outcome was present in >20% of high/very-high-risk patients (score +4 to+11) including 4%-6% deaths. The online calculator and the pictorial aids can be found at: https://teamvenk.com/csrs CONCLUSIONS: 30-day observed risk estimates from a large cohort of patients can be obtained for management decision-making. Our work suggests very-low-risk and low-risk patients may be discharged, discussion with patients regarding investigations and disposition are needed for medium-risk patients, and high-risk patients should be hospitalised. The online calculator, accompanied by pictorial decision aids for the CSRS, may assist in discussion with patients.

4.
Ann Emerg Med ; 2021 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-34756448

RESUMO

STUDY OBJECTIVE: Primary headache disorders are prevalent and account for 2% of all emergency department visits. Current treatment options are effective; however, time to pain relief is suboptimal. Alternatives such as peripheral nerve blocks have shown promising results. The objective of this systematic review is to examine the effectiveness of peripheral nerve blocks for timely pain relief. METHODS: We searched Ovid MEDLINE, EMBASE, Web of Science Core Collection, and the Cochrane Central Register of Controlled Trials and included randomized controlled trials comparing peripheral nerve blocks to placebo or active therapy. The primary outcome was pain within 120 minutes. Secondary outcomes were pain after 120 minutes, adverse events, need for rescue medications, and relapse of headache. Two reviewers screened and extracted data independently; mean differences (MDs) were calculated, and results were pooled using a random-effects model. RESULTS: Eleven studies met our eligibility criteria (n=860), of which 9 were included in the meta-analysis. Pain scores were significantly lower in patients treated with peripheral nerve blocks than with placebo at 15 minutes (MD: -1.17; 95% confidence interval: -1.82 to -0.51) and 30 minutes (MD: -0.99; 95% confidence interval: -1.66 to -0.32), and no serious adverse events were reported. Pain scores for peripheral nerve blocks versus active therapy and secondary outcomes were not pooled due to clinical heterogeneity. CONCLUSION: Our review shows peripheral nerve blocks are effective as a rapid treatment option when compared to placebo; however, we were unable to assess effectiveness against standard treatment. Emergency physicians should consider peripheral nerve blocks as an adjunct therapy for patients with primary headache disorders.

5.
J Med Ethics ; 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34782417

RESUMO

OBJECTIVES: To describe reporting of informed consent in pragmatic trials, justifications for waivers of consent and reporting of alternative approaches to standard written consent. To identify factors associated with (1) not reporting and (2) not obtaining consent. METHODS: Survey of primary trial reports, published 2014-2019, identified using an electronic search filter for pragmatic trials implemented in MEDLINE, and registered in ClinicalTrials.gov. RESULTS: Among 1988 trials, 132 (6.6%) did not include a statement about participant consent, 1691 (85.0%) reported consent had been obtained, 139 (7.0%) reported a waiver and 26 (1.3%) reported consent for one aspect (eg, data collection) but a waiver for another (eg, intervention). Of the 165 trials reporting a waiver, 76 (46.1%) provided a justification. Few (53, 2.9%) explicitly reported use of alternative approaches to consent. In multivariable logistic regression analyses, lower journal impact factor (p=0.001) and cluster randomisation (p<0.0001) were significantly associated with not reporting on consent, while trial recency, cluster randomisation, higher-income country settings, health services research and explicit labelling as pragmatic were significantly associated with not obtaining consent (all p<0.0001). DISCUSSION: Not obtaining consent seems to be increasing and is associated with the use of cluster randomisation and pragmatic aims, but neither cluster randomisation nor pragmatism are currently accepted justifications for waivers of consent. Rather than considering either standard written informed consent or waivers of consent, researchers and research ethics committees could consider alternative consent approaches that may facilitate the conduct of pragmatic trials while preserving patient autonomy and the public's trust in research.

6.
Biometrics ; 2021 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-34719017

RESUMO

The stepped wedge cluster randomized trial (SW-CRT) is an increasingly popular design for evaluating health service delivery or policy interventions. An essential consideration of this design is the need to account for both within-period and between-period correlations in sample size calculations. Especially when embedded in health care delivery systems, many SW-CRTs may have subclusters nested in clusters, within which outcomes are collected longitudinally. However, existing sample size methods that account for between-period correlations have not allowed for multiple levels of clustering. We present computationally efficient sample size procedures that properly differentiate within-period and between-period intracluster correlation coefficients in SW-CRTs in the presence of subclusters. We introduce an extended block exchangeable correlation matrix to characterize the complex dependencies of outcomes within clusters. For Gaussian outcomes, we derive a closed-form sample size expression that depends on the correlation structure only through two eigenvalues of the extended block exchangeable correlation structure. For non-Gaussian outcomes, we present a generic sample size algorithm based on linearization and elucidate simplifications under canonical link functions. For example, we show that the approximate sample size formula under a logistic linear mixed model depends on three eigenvalues of the extended block exchangeable correlation matrix. We provide an extension to accommodate unequal cluster sizes and validate the proposed methods via simulations. Finally, we illustrate our methods in two real SW-CRTs with subclusters.

7.
BMJ Open ; 11(9): e052843, 2021 09 23.
Artigo em Inglês | MEDLINE | ID: mdl-34556517

RESUMO

OBJECTIVES: Response rates to physician surveys are typically low. The objective of this study was to determine the effect of a prenotification letter on the response rate of a postal survey of emergency physicians. DESIGN: This was a substudy of a national, cross-sectional postal survey sent to emergency physicians in Canada. We randomised participants to either receive a postal prenotification letter prior to the survey, or to no prenotification letter. PARTICIPANTS: A random sample of 500 emergency physicians in Canada. Participants were selected from the Canadian Medical Directory, a national medical directory which lists more than 99% of practising physicians in Canada. INTERVENTIONS: Using computer-generated randomisation, physicians were randomised in a concealed fashion to receive a prenotification letter approximately 1 week prior to the survey, or to not receive a prenotification letter. All physicians received an unconditional incentive of a $3 coffee card with the survey instrument. In both groups, non-respondents were sent reminder surveys approximately every 14 days and a special contact using Xpresspost during the final contact attempt. OUTCOME: The primary outcome was the survey response rate. RESULTS: 201 of 447 eligible physicians returned the survey (45.0%). Of 231 eligible physicians contacted in the prenotification group, 80 (34.6%) returned the survey and among 237 eligible physicians contacted in the no-prenotification group, 121 (51.1%) returned the survey (absolute difference in proportions 16.5%, 95% CI 2.5 to 30.5, p=0.01). CONCLUSION: Inclusion of a prenotification letter resulted in a lower response rate in this postal survey of emergency physicians. Given the added costs, time and effort required to send a prenotification letter, this study suggests that it may be more effective to omit the prenotification letter in physician postal surveys.


Assuntos
Médicos , Serviços Postais , Canadá , Estudos Transversais , Humanos , Inquéritos e Questionários
8.
CJEM ; 23(6): 812-819, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34468970

RESUMO

BACKGROUND: Transient ischemic attack (TIA) and non-disabling stroke are common emergency department (ED) presentations. Currently, there are no prospective multicenter studies determining predictors of neurologists confirming a diagnosis of cerebral ischemia in patients discharged with a diagnosis of TIA or stroke. The objectives were to (1) calculate the concordance between emergency physicians and neurologists for the outcome of diagnosing TIA or stroke, and (2) identify characteristics associated with neurologists diagnosing a stroke mimic. METHODS: This was a planned sub-study of a prospective cohort study at 14 Canadian EDs enrolling patients diagnosed with TIA or non-disabling stroke from 2006 to 2017. Logistic regression was used to identify factors associated with neurologists' diagnosis of cerebral ischemia. Our primary outcome was the composite outcome of cerebral ischemia (TIA or non-disabling stroke) based on the neurologists' assessment. RESULTS: The diagnosis of cerebral ischemia was confirmed by neurologists in 5794 patients (55.4%). The most common identified stroke mimics were migraine (18%), peripheral vertigo (7%), syncope (4%), and seizure (3%). Over a third of patients (38.4%) ultimately had an undetermined aetiology for their symptoms. The strongest predictors of cerebral ischemia confirmation were infarct on CT (OR 1.83, 95% CI 1.65-2.02), advanced age (OR comparing 75th-25th percentiles 1.67, 1.55-1.80), language disturbance (OR 1.92, 1.75-2.10), and smoking (OR 1.67, 1.46-1.91). The strongest predictors of stroke mimics were syncope (OR 0.59, 0.48-0.72), vertigo (OR 0.52, 0.45-0.59), bilateral symptoms (OR 0.60, 0.50-0.72), and confusion (OR 0.50, 0.44-0.57). CONCLUSION: Physicians should have a high index of suspicion of cerebral ischemia in patients with advanced age, smoking history, language disturbance, or infarcts on CT. Physicians should discriminate in which patients to pursue stroke investigations on when deemed at minimal risk of cerebral ischemia, including those with isolated vertigo, syncope, or bilateral symptoms.

9.
Can J Cardiol ; 37(11): 1775-1782, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34474123

RESUMO

BACKGROUND: We sought to evaluate safety of electrical cardioversion (ECV) for patients with acute atrial fibrillation (AF) or atrial flutter (AFL) in the emergency department (ED). METHODS: This was an analysis of data from 4 multicentre AF/AFL studies conducted from 2008 to 2019 at 23 large EDs. We included adult patients who received attempts at ECV and who had presented acutely after symptom onset. Staff manually reviewed study and clinical records to abstract data. RESULTS: We evaluated 1736 ECV cases with a mean age of 60.1 years and 67.1% male. The overall success of ECV was 90.2% (95% confidence interval 88.7%-91.6%), with 4.9% of patients admitted. ED physicians performed the ECV in 95.2% and provided sedation in 96.5%; 13.9% (12.3%-15.7%) of cases experienced important adverse events that required treatment, and 0.4% were classified as life threatening. Another 5.6% had adverse events that did not require treatment. Logistic regression found that the RAFF-3 study cohort (odds ratio [OR] 2.0), age ≥ 85 years (OR 2.1), coronary artery disease (OR 1.5), midazolam (OR 1.9), and fentanyl (OR 1.5) were associated with important adverse events. CONCLUSIONS: This large evaluation of the safety of ECV for acute AF/AFL in the ED found that while serious adverse events were rare, there were a concerning number of events following sedation that required intervention. Physicians should be aware that older age, coronary artery disease, and fentanyl are associated with higher risks of important adverse events. This study provides more information for shared decision making discussions with patients when choosing between drug-shock and shock-only cardioversion strategies.

10.
BMJ Open ; 11(9): e054213, 2021 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-34580104

RESUMO

In a cluster randomised trial (CRT), intact groups-such as communities, clinics or schools-are randomised to the study intervention or control conditions. The issue of informed consent in CRTs has been particularly challenging for researchers and research ethics committees. Some argue that cluster randomisation is a reason not to seek informed consent from research participants. In fact, systematic reviews have found that, relative to individually randomised trials, CRTs are associated with an increased likelihood of inadequate reporting of consent procedures and inappropriate use of waivers of consent. The objective of this paper is to clarify this confusion by providing a practical and useful framework to guide researchers and research ethics committees through consent issues in CRTs. In CRTs, it is the unit of intervention-not the unit of randomisation-that drives informed consent issues. We explicate a three-step framework for thinking through informed consent in CRTs: (1) identify research participants, (2) identify the study element(s) to which research participants are exposed, and (3) determine if a waiver of consent is appropriate for each study element. We then apply our framework to examples of CRTs of cluster-level, professional-level and individual-level interventions, and provide key lessons on informed consent for each type of CRT.


Assuntos
Ética em Pesquisa , Projetos de Pesquisa , Comitês de Ética em Pesquisa , Humanos , Consentimento Livre e Esclarecido , Ensaios Clínicos Controlados Aleatórios como Assunto , Pesquisadores
11.
CJEM ; 23(5): 631-640, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34351598

RESUMO

OBJECTIVES: Clinical decision support may facilitate evidence-based imaging, but most studies to date examining the impact of decision support have used non-randomized designs which limit the conclusions that can be drawn from them. This randomized trial examines if decision support can reduce computed tomography (CT) utilization for patients with mild traumatic brain injuries and suspected pulmonary embolism in the emergency department. This study was funded by a competitive public research grant and registered on ClinicalTrials.gov (NCT02410941). METHODS: Emergency physicians at five urban sites were assigned to voluntary decision support for CT imaging of patients with either head injuries or suspected pulmonary embolism using a cluster-randomized design over a 1-year intervention period. The co-primary outcomes were CT head and CT pulmonary angiography utilization. CT pulmonary angiography diagnostic yield (proportion of studies diagnostic for acute pulmonary embolism) was a secondary outcome. RESULTS: A total of 225 physicians were randomized and studied over a 2-year baseline and 1-year intervention period. Physicians interacted with the decision support in 38.0% and 45.0% of eligible head injury and suspected pulmonary embolism cases, respectively. A mixed effects logistic regression model demonstrated no significant impact of decision support on head CT utilization (OR 0.93, 95% CI 0.79-1.10, p = 0.31), CT pulmonary angiography utilization (OR 0.98, 95% CI 0.88-1.11, p = 0.74) or diagnostic yield (OR 1.23, 95% CI 0.96-1.65, p = 0.10). However, overall CT pulmonary diagnostic yield (17.7%) was almost three times higher than that reported by a recent large US study, suggesting that selective imaging was already being employed. CONCLUSION: Voluntary decision support addressing many commonly cited barriers to evidence-based imaging did not significantly reduce CT utilization or improve diagnostic yield but was limited by low rates of participation and high baseline rates of selective imaging. Demonstrating value to clinicians through interventions that improve workflow is likely necessary to meaningfully change imaging practices.


Assuntos
Sistemas de Apoio a Decisões Clínicas , Embolia Pulmonar , Angiografia , Serviço Hospitalar de Emergência , Humanos , Embolia Pulmonar/diagnóstico por imagem , Tomografia Computadorizada por Raios X
12.
Can J Kidney Health Dis ; 8: 20543581211032818, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34367647

RESUMO

Background: Cluster randomized trials (CRTs) are trials in which intact groups such as hemodialysis centers or shifts are randomized to treatment or control arms. Pragmatic CRTs have been promoted as a promising trial design for nephrology research yet may also pose ethical challenges. While randomization occurs at the cluster level, the intervention and data collection may vary in a CRT, challenging the identification of research participants. Moreover, when a waiver of patient consent is granted by a research ethics committee, there is an open question as to whether and to what degree patients should be notified about ongoing research or be provided with a debrief regarding the nature and results of the trial upon completion. While empirical and conceptual research exploring ethical issues in pragmatic CRTs has begun to emerge, there has been limited discussion with patients, families, or caregivers of patients undergoing hemodialysis. Objective: To explore with patients and families with experience of hemodialysis research the challenges raised by different approaches to designing pragmatic CRTs in hemodialysis. Specifically, their perceptions of (1) the use of a waiver of consent, (2) notification processes and information provided to participants, and (3) any other concerns about cluster randomized designs in hemodialysis. Design: Focus group and interview discussions of hypothetical clinical trial designs. Setting: Focus groups and interviews were conducted in-person or via videoconference or telephone. Participants: Patient partners in hemodialysis research, defined as patients with personal experience of dialysis or a family member who had experience supporting a patient receiving hemodialysis, who have been actively involved in discussions to advise a research team on the design, conduct, or implementation of a hemodialysis trial. Methods: Participants were invited to participate in focus groups or individual discussions that were audio recorded with consent. Recorded interviews were transcribed verbatim prior to analysis. Transcripts were analyzed using a thematic analysis approach. Results: Two focus groups, three individual interviews, and one interview involving a patient and family member were conducted with 17 individuals between February 2019 and May 2020. Participants expressed support for approaches that emphasized patient choice. Disclosure of patient-relevant risks and information were key themes. Both consent and notification processes served to generate trust, but bypassing patient choice was perceived as undermining this trust. Participants did not dismiss the option of a waiver of consent. They were, however, more restrictive in their views about when a waiver of consent may be acceptable. Patient partners were skeptical of claims to impracticability based on costs or the time commitments for staff. Limitations: All participants were from Canada and had been involved in the design or conduct of a trial, limiting the degree to which results may be extrapolated. Conclusions: Given the preferences of participants to be afforded the opportunity to decide about trial participation, we argue that investigators should thoroughly investigate approaches that allow participants to make an informed choice regarding trial participation. In keeping with the preference for autonomous choice, there remains a need to further explore how consent approaches can be designed to facilitate clinical trial conduct while meeting their ethical requirements. Finally, further work is needed to define the limited circumstances in which waivers of consent are appropriate.

13.
CJC Open ; 3(7): 913-923, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34401698

RESUMO

Background: The objective of this study was to evaluate adherence to guideline-recommended cardiac secondary prevention therapies by immigration and ethnicity. Methods: We conducted a retrospective substudy of the Interventions Supporting Long-Term Adherence and Decreasing Cardiovascular Events (ISLAND) randomized controlled trial. A cohort of 1642 participants was analyzed. Patients were categorized based on their self-reported immigrant status as being Canadian or foreign born and based on their visual minority status (as European or a visual minority). We used logistic regression to examine associations between these patient characteristics of interest and patient adherence to statin medication 1 year after myocardial infarction (MI) and completion of cardiac rehabilitation, adjusting for age, sex, and comorbidities. Results: The dataset included outcome data on 1049 (64%) Canadian-born patients and 593 (36%) immigrants. There were 347 (21%) who identified as a visual minority. We report a nonsignificant trend in statin adherence 1 year after MI favouring foreign-born participants compared with Canadian-born participants (odds ratio [OR], 1.26; 95% confidence interval [CI], 0.91-1.68). Visual minorities were found to have no significant difference in statin adherence 1 year after MI compared with participants of European ethnicity (OR, 1.04; 95% CI, 0.72-1.51). Neither immigration status (OR, 0.91; 95% CI, 0.72-1.15) nor visual minority status (OR, 0.97; 95% CI, 0.73-1.28) were associated with cardiac rehabilitation completion. Conclusions: Our findings offer limited support that immigrants with > 10 years of Canadian residency exposure experience greater adherence to statins 1 year after MI. Further research is required to better inform our understanding of secondary prevention strategy among immigrant populations.

14.
BMC Med Res Methodol ; 21(1): 181, 2021 08 28.
Artigo em Inglês | MEDLINE | ID: mdl-34454418

RESUMO

BACKGROUND: Interrupted time series (ITS) studies are frequently used to evaluate the effects of population-level interventions or exposures. However, examination of the performance of statistical methods for this design has received relatively little attention. METHODS: We simulated continuous data to compare the performance of a set of statistical methods under a range of scenarios which included different level and slope changes, varying lengths of series and magnitudes of lag-1 autocorrelation. We also examined the performance of the Durbin-Watson (DW) test for detecting autocorrelation. RESULTS: All methods yielded unbiased estimates of the level and slope changes over all scenarios. The magnitude of autocorrelation was underestimated by all methods, however, restricted maximum likelihood (REML) yielded the least biased estimates. Underestimation of autocorrelation led to standard errors that were too small and coverage less than the nominal 95%. All methods performed better with longer time series, except for ordinary least squares (OLS) in the presence of autocorrelation and Newey-West for high values of autocorrelation. The DW test for the presence of autocorrelation performed poorly except for long series and large autocorrelation. CONCLUSIONS: From the methods evaluated, OLS was the preferred method in series with fewer than 12 points, while in longer series, REML was preferred. The DW test should not be relied upon to detect autocorrelation, except when the series is long. Care is needed when interpreting results from all methods, given confidence intervals will generally be too narrow. Further research is required to develop better performing methods for ITS, especially for short series.


Assuntos
Projetos de Pesquisa , Humanos , Análise de Séries Temporais Interrompida , Análise dos Mínimos Quadrados
15.
CMAJ ; 193(26): E997-E1005, 2021 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-34226263

RESUMO

BACKGROUND: Prognostication tools that report personalized mortality risk and survival could improve discussions about end-of-life and advance care planning. We sought to develop and validate a mortality risk model for older adults with diverse care needs in home care using self-reportable information - the Risk Evaluation for Support: Predictions for Elder-Life in the Community Tool (RESPECT). METHODS: Using a derivation cohort that comprised adults living in Ontario, Canada, aged 50 years and older with at least 1 Resident Assessment Instrument for Home Care (RAI-HC) record between Jan. 1, 2007, and Dec. 31, 2012, we developed a mortality risk model. The primary outcome was mortality 6 months after a RAI-HC assessment. We used proportional hazards regression with robust standard errors to account for clustering by the individual. We validated this algorithm for a second cohort of users of home care who were assessed between Jan. 1 and Dec. 31, 2013. We used Kaplan-Meier survival curves to estimate the observed risk of death at 6 months for assessment of calibration and median survival. We constructed 61 risk groups based on incremental increases in the estimated median survival of about 3 weeks among adults at high risk and 3 months among adults at lower risk. RESULTS: The derivation and validation cohorts included 435 009 and 139 388 adults, respectively. We identified a total of 122 823 deaths within 6 months of a RAI-HC assessment in the derivation cohort. The mean predicted 6-month mortality risk was 10.8% (95% confidence interval [CI] 10.7%-10.8%) and ranged from 1.54% (95% CI 1.53%-1.54%) in the lowest to 98.1% (95% CI 98.1%-98.2%) in the highest risk group. Estimated median survival spanned from 28 days (11 to 84 d at the 25th and 75th percentiles) in the highest risk group to over 8 years (1925 to 3420 d) in the lowest risk group. The algorithm had a c-statistic of 0.753 (95% CI 0.750-0.756) in our validation cohort. INTERPRETATION: The RESPECT mortality risk prediction tool that makes use of readily available information can improve the identification of palliative and end-of-life care needs in a diverse older adult population receiving home care.

16.
Drug Alcohol Rev ; 2021 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-34250645

RESUMO

INTRODUCTION: This study describes the legal recreational cannabis market across Canada over the 2 years following legalisation. We compared changes in access to the legal cannabis retail market for all provinces and territories (jurisdictions) in Canada and explored differences between jurisdictions. METHODS: We collected data for all legal cannabis stores in Canada over five time periods following legalisation in October 2018. We examined the following measures by jurisdiction and retail model (public vs. private operation): absolute and per capita store numbers, hours of operation and store access across neighbourhoods. RESULTS: Two years following legalisation, there were a total of 1183 legal cannabis stores open across Canada (3.7 stores per 100 000 individuals aged 15+). There was wide variation between jurisdictions in access to retail stores, with the lowest stores per capita in Quebec and Ontario (0.6 and 1.6 per 100 000), and the highest in Alberta and Yukon (14.3 per 100 000 in both). Jurisdictions with private retail models had more stores (4.8 vs. 1.0 per 100 000), held greater median weekly hours (80 vs. 69) and experienced greater store growth over time compared to public models. After adjusting for confounders, there were 1.96 times (95% confidence intervals: 1.84, 2.09) more cannabis stores within 1000 m of the lowest- compared to the highest-income quintile neighbourhoods. DISCUSSION AND CONCLUSIONS: While access to the recreational cannabis retail market has increased following legalisation, there is substantial variation in access between jurisdictions and evidence of concentration in lower-income neighbourhoods. These differences may contribute to disparities in cannabis use and harms.

17.
J Clin Epidemiol ; 138: 102-114, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34229091

RESUMO

BACKGROUND AND OBJECTIVE: Feasibility studies are increasingly being used to support the development of, and investigate uncertainties around, future large-scale trials. The future trial can be designed with either a pragmatic or explanatory mindset. Whereas pragmatic trials aim to inform the choice between different care options and thus, are designed to resemble conditions outside of a clinical trial environment, explanatory trials examine the benefit of a treatment under more controlled conditions. There is existing guidance for designing feasibility studies, but none that explicitly considers the goals of pragmatic designs. We aimed to identify unique areas of uncertainty that are relevant to planning a pragmatic trial. RESULTS: We identified ten relevant domains, partly based on the pragmatic-explanatory continuum indicator summary-2 (PRECIS-2) framework, and describe potential questions of uncertainty within each: intervention development, research ethics, participant identification and eligibility, recruitment of individuals, setting, organization, flexibility of delivery, flexibility of adherence, follow-up, and importance of primary outcome to patients and decision-makers. We present examples to illustrate how uncertainty in these domains might be addressed within a feasibility study. CONCLUSION: Researchers planning a feasibility study in advance of a pragmatic trial should consider feasibility objectives specifically relevant to areas of uncertainty for pragmatic trials.


Assuntos
Pesquisa Biomédica/estatística & dados numéricos , Pesquisa Biomédica/normas , Ensaios Clínicos Pragmáticos como Assunto/estatística & dados numéricos , Ensaios Clínicos Pragmáticos como Assunto/normas , Projetos de Pesquisa/estatística & dados numéricos , Projetos de Pesquisa/normas , Incerteza , Estudos de Viabilidade , Guias como Assunto , Humanos , Projetos Piloto
19.
J Clin Epidemiol ; 138: 49-59, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34197941

RESUMO

OBJECTIVES: To describe the prevalence of risks of bias in cluster-randomized trials of individual-level interventions, according to the Cochrane Risk of Bias tool. STUDY DESIGN AND SETTING: Review undertaken in duplicate of a random sample of 40 primary reports of cluster-randomized trials of individual-level interventions. RESULTS: The most common reported reasons for adopting cluster randomization were the need to avoid contamination (17, 42.5%) and practical considerations (14, 35%). Of the 40 trials all but one was assessed as being at risk of bias. A majority (27, 67.5%) were assessed as at risk due to the timing of identification and recruitment of participants; many (21, 52.5%) due to an apparent lack of adequate allocation concealment; and many due to selectively reported results (22, 55%), arising from a mixture of reasons including lack of documentation of primary outcome. Other risks mostly occurred infrequently. CONCLUSION: Many cluster-randomized trials evaluating individual-level interventions appear to be at risk of bias, mostly due to identification and recruitment biases. We recommend that investigators carefully consider the need for cluster randomization; follow recommended procedures to mitigate risks of identification and recruitment bias; and adhere to good reporting practices including clear documentation of primary outcome and allocation concealment methods.


Assuntos
Pesquisa Biomédica/normas , Viés de Publicação/estatística & dados numéricos , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Ensaios Clínicos Controlados Aleatórios como Assunto/normas , Projetos de Pesquisa/estatística & dados numéricos , Projetos de Pesquisa/normas , Relatório de Pesquisa/normas , Guias como Assunto , Humanos
20.
Pediatrics ; 148(2)2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34266901

RESUMO

BACKGROUND: Evidence to guide treatment of pediatric medium-chain acyl-coenzyme A dehydrogenase (MCAD) deficiency and phenylketonuria (PKU) is fragmented because of large variability in outcome selection and measurement. Our goal was to develop core outcome sets (COSs) for these diseases to facilitate meaningful future evidence generation and enhance the capacity to compare and synthesize findings across studies. METHODS: Parents and/or caregivers, health professionals, and health policy advisors completed a Delphi survey and participated in a consensus workshop to select core outcomes from candidate lists of outcomes for MCAD deficiency and PKU. Delphi participants rated the importance of outcomes on a nine-point scale (1-3: not important, 4-6: important but not critical, 7-9: critical). Candidate outcomes were progressively narrowed down over 3 survey rounds. At the workshop, participants evaluated the remaining candidate outcomes using an adapted nominal technique, open discussion, and voting. After the workshop, we finalized the COSs and recommended measurement instruments for each outcome. RESULTS: There were 85, 61, and 53 participants across 3 Delphi rounds, respectively. The candidate core outcome lists were narrowed down to 20 outcomes per disease to be discussed at the consensus workshop. Voting by 18 workshop participants led to COSs composed of 8 and 9 outcomes for MCAD deficiency and PKU, respectively, with measurement recommendations. CONCLUSIONS: These are the first known pediatric COSs for MCAD deficiency and PKU. Adoption in future studies will help to ensure best use of limited research resources to ultimately improve care for children with these rare diseases.

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