[Show abstract][Hide abstract] ABSTRACT: Pneumonia is responsible for a large proportion of hospital admissions and antibiotic utilization. Physician adherence to evidence-based pneumonia management guidelines is poor. Antimicrobial stewardship programs (ASPs) are an effective intervention to mitigate against unwarranted variation from these guidelines. Despite this benefit, ASPs have not been shown to reduce the length of stay of hospitalized patients with pneumonia. In immune-competent adult patients admitted to a hospital ward with a diagnosis of community-acquired pneumonia, does a multi-faceted ASP utilizing prospective chart audit and feedback reduce the length of stay, compared with usual care, without increasing the risk of death or readmission 30 days after discharge from hospital?
Starting on 1 April 2013, all consecutive immune-competent adult patients (>18 years old) admitted to a hospital ward with a positive febrile respiratory illness screening questionnaire and a diagnosis of pneumonia by the attending physician will be eligible for inclusion in this non-randomized study. All eligible patients who fulfill the ASP review criteria will undergo a prospective chart audit, followed by an ASP recommendation provided to the attending physician. The attending physician is responsible for implementing or rejecting the ASP recommendation. This is a modified stepped-wedge design with a baseline data collection period of 3 months, followed by non-random sequential introduction of the ASP intervention on each of four hospital wards in a single community-based, academic-affiliated 339-bed acute-care hospital in Barrie, ON, Canada. The primary outcome measure is hospital length of stay; secondary outcome measures include days and duration of antibiotic therapy, and inadvertent adverse outcomes of 30 day post-discharge mortality and hospital readmission rates. Differences in outcome measures will be assessed using extended Cox regression analysis. Time to ASP intervention is included as a time-dependent covariate in the final model, to account for time-dependent bias.
By designing a pragmatic clinical trial with unique design and analytic features, we not only expect to demonstrate the effectiveness of a real-world ASP, but also provide a model for program evaluation that can be used more broadly to improve patient safety and quality of care.
ClinicalTrials.gov NCT02264756 .
[Show abstract][Hide abstract] ABSTRACT: Suicidal behavior is a growing public health concern resulting in morbidity and premature death. Although certain factors such as age, sex, and psychiatric disorders have been consistently reported to be associated with suicidal behavior, other factors including biological markers, diet, and physical activity may also influence suicidal behavior. The purpose of this pilot study was to evaluate the feasibility of conducting a full-scale study to identify the conventional and novel risk factors of suicidal behavior in individuals who made a recent suicide attempt.
This pilot study was a case-control study of participants with recent (within 1 month of admission) suicide attempts admitted to hospital and compared to two control groups: 1) psychiatric inpatient participants without a history of suicide attempts and 2) community-based controls. We collected information on demographic variables, circumstances of suicide attempts (for cases), medical and psychiatric diagnoses, behavioral patterns, physical measurements, and social factors. Blood and urine samples were also collected for biological markers. Feasibility outcomes are as follows: 1) 50 % of all eligible cases will consent to participate, 2) 50 cases and 100 controls per year can be recruited, and 3) at least 80 % of the participants will provide blood samples for DNA and biological markers.
We recruited 179 participants in total; 51 cases, 57 psychiatric controls without suicide attempt, and 71 non-psychiatric controls in Hamilton, Ontario. Recruitment rate was 70 % (213/304), and we obtained urine and blood specimens from 90 % (191/213) of participants. Questionnaire completion rates were high, and data quality was very good with few data-related queries to resolve. We learned that cases tended to be hospitalized for long periods of time and the suicide attempt occurred more than a month ago in many of the cases; therefore, we expanded our inclusion criterion related to timing of suicide attempt to 3 months instead of 1 month.
The study procedures needed certain modifications including extending the time between suicide attempt and date of recruitment, and more detailed questionnaires related to diet were necessary while other questionnaires such as social support needed to be shortened. Overall, this study showed that it is feasible to conduct a larger-scale study.
[Show abstract][Hide abstract] ABSTRACT: Background
Polycystic ovarian syndrome (PCOS) is a common reproductive endocrine disease that is seen among adolescent women. Currently, there is limited evidence to support treatment options leading to considerable variation in practice among healthcare specialists. The objective of this study is to review and synthesize all the available evidence on treatment options for PCOS among adolescent women.
We will conduct a systematic review of all randomized controlled trials evaluating the use of metformin, oral contraceptive pills as monotherapy, or as combination with pioglitazone, spironolactone, flutamide, and lifestyle interventions in the treatment of PCOS in adolescent women ages 11 to 19 years. The primary outcome measures are menstrual regulation and change hirsutism scores. The secondary outcome measures include acne scores, prevalence of dysglycaemia, BMI, lipid profile, total testosterone level, and adverse events. We will perform literature searches through Ovid Medline, Ovid Embase, and Cochrane Central Register of Controlled Trials (CENTRAL), and gray literature resources. Two reviewers will independently screen titles and abstracts of identified citations, review the full texts of potentially eligible trials, extract information from eligible trials, and assess the risk of bias and quality of the evidence independently. Results of this review will be summarized narratively and quantitatively as appropriate. We will perform a multiple treatment comparison using network meta-analysis to estimate the pooled direct and indirect effects for all PCOS interventions on outcomes if adequate data is available.
PCOS treatment poses a clinical challenge to the patients and physicians. This is the first systematic review and network meta-analysis for PCOS treatment in adolescents. We expect that our results will help improve patient care, unify the treatment approaches among specialists, and encourage research for other therapeutic options.
Systematic review registration
[Show abstract][Hide abstract] ABSTRACT: Background
The consequences of opioid relapse among patients being treated with opioid substitution treatment (OST) are serious and can result in abnormal cardiovascular function, overdose, and mortality. Chronic pain is a major risk factor for opioid relapse within the addiction treatment setting. There exist a number of opioid maintenance therapies including methadone, buprenorphine, naltrexone, and levomethadyl acetate (LAAM), of which the mediating effects of pain on treatment attrition, substance use behavior, and social functioning may differ across therapies. We aim to 1) evaluate the impact of pain on the treatment outcomes of addiction patients being managed with OST and 2) identify the most recently published opioid maintenance treatment guidelines from the United States, Canada, and the UK to determine how the evidence is being translated into clinical practice.
The authors will search Medline, EMBASE, PubMed, PsycINFO, Web of Science, Cochrane Database of Systematic Reviews, ProQuest Dissertations and theses Database, Cochrane Central Register of Controlled Trials (CENTRAL), World Health Organization International Clinical Trials Registry Platform Search Portal, and the National Institutes for Health Clinical Trials Registry. We will search www.guidelines.gov and the National Institute for Care and Excellence (NICE) databases to identify the most recently published OST guidelines. All screening and data extraction will be completed in duplicate. Provided the data are suitable, we will perform a multiple treatment comparison using Bayesian meta-analytic methods to produce summary statistics estimating the effect of chronic pain on all OSTs. Our primary outcome is substance use behavior, which includes opioid and non-opioid substance use. We will also evaluate secondary endpoints such as treatment retention, general physical health, intervention adherence, personal and social functioning, as well as psychiatric symptoms.
This review will capture the experience of treatment outcomes for a sub-population of opioid addiction patients and provide an opportunity to distinguish the best quality guidelines for OST. If chronic pain truly does result in negative consequences for opioid addiction patients, it is important we identify which OSTs are most appropriate for chronic pain patients as well as ensure the treatment guidelines incorporate this information.
Systematic review registration
PROSPERO CRD42014014015 http://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42014014015#.VS1Qw1wkKGM
[Show abstract][Hide abstract] ABSTRACT: The lumbar transversus abdominis plane (TAP) block has become an optional part of multimodal analgesia following several abdominal surgeries. There remains a lack of consensus regarding the extent of dermatomal blockade following lumber TAP block, as well as the optimal local anesthetic volumes and concentrations. The objectives of this pilot trial were to assess the feasibility of conducting a similar full-scale trial and gather information on relevant clinical outcomes, namely whether greater local anesthetic volumes would lead to more cephalad dermatomal blockade.
The study was a prospective, double-blinded pilot randomized controlled trial (RCT) with three arms, each representing different local anesthetic volumes: 20 ml 0.5% ropivacaine, 30 ml 0.33% ropivacaine, and 40 ml 0.25% ropivacaine. We planned to recruit 30 females undergoing total abdominal hysterectomy for non-malignant pathology, who would then receive bilateral ultrasound-guided midaxillary TAP blocks at the completion of surgery. Randomized patients would be followed for 48 h post-block and would receive multimodal analgesia. The primary outcomes were measurements of patient recruitment and safety, to inform the feasibility of a larger trial. The main secondary outcome was the clinically pertinent endpoint of dermatomal blockade, which was assessed by loss of sensation to ice and pinprick.
Our target sample size was reached in 8 months, and the recruitment rate was 52% (31/60). A total of 58 TAP blocks were performed among 29 patients. All but one of the patients who received interventions were successfully followed and assessed up to 48 h. No patient safety-related adverse events were reported during the study period. The mean highest dermatome blocked in each group at any time point was T8. The 20 ml 0.5% ropivacaine group achieved a T9–L1 block that lasted for 48 h. The 30 ml 0.33% ropivacaine group had a sensory block from T9–L1 that regressed to T10–T12 between 24 and 48 h. The 40 ml 0.25% ropivacaine group reported an initial sensory block from T9–T12 that regressed by 24 h to include only the T12 dermatome.
This pilot study demonstrated that the study design is feasible and safe to be carried to a full-scale RCT. The preliminary clinical findings showed that increasing the volume, while maintaining a constant dose, of local anesthetic does not appear to extend the height of dermatomal blockade following midaxillary TAP block. This finding needs to be confirmed in future studies.
ClinicalTrials.gov registration is: NCT01307215.
[Show abstract][Hide abstract] ABSTRACT: Objective:
Many strong recommendations issued by the World Health Organization (WHO) are based on low or very low quality (low certainty) evidence (discordant recommendations). Many such discordant recommendations are inconsistent with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidance. We sought to understand why WHO makes discordant recommendations inconsistent with GRADE guidance.
Study design and setting:
We interviewed panel members involved in guidelines approved by WHO (2007-2012) that included discordant recommendations. Interviews, recorded and transcribed, focused on use of GRADE including the reasoning underlying, and factors contributing to, discordant recommendations.
Four themes emerged: strengths of GRADE, challenges and barriers to GRADE, strategies to improve GRADE application, and explanations for discordant recommendations. Reasons for discordant recommendations included skepticism about the value of making conditional recommendations; political considerations; high certainty in benefits (sometimes warranted, sometimes not) despite assessing evidence as low certainty; and concerns that conditional recommendations will be ignored.
WHO panelists make discordant recommendations inconsistent with GRADE guidance for reasons that include limitations in their understanding of GRADE. Ensuring optimal application of GRADE at WHO and elsewhere likely requires selecting panelists who have a commitment to GRADE principles, additional training of panellists, and formal processes to maximize adherence to GRADE principles.
Journal of clinical epidemiology 09/2015; DOI:10.1016/j.jclinepi.2015.09.006 · 3.42 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Failure to recognize the presence of competing risk or to account for it may result in misleading conclusions. We aimed to perform a competing risk analysis to assess the efficacy of the low molecular weight heparin dalteparin versus unfractionated heparin (UFH) in venous thromboembolism (VTE) in medical-surgical critically ill patients, taking death as a competing risk.This was a secondary analysis of a prospective randomized study of the Prophylaxis for Thromboembolism in Critical Care Trial (PROTECT) database. A total of 3746 medical-surgical critically ill patients from 67 intensive care units (ICUs) in 6 countries receiving either subcutaneous UFH 5000 IU twice daily (n = 1873) or dalteparin 5000 IU once daily plus once-daily placebo (n = 1873) were included for analysis.A total of 205 incident proximal leg deep vein thromboses (PLDVT) were reported during follow-up, among which 96 were in the dalteparin group and 109 were in the UFH group. No significant treatment effect of dalteparin on PLDVT compared with UFH was observed in either the competing risk analysis or standard survival analysis (also known as cause-specific analysis) using multivariable models adjusted for APACHE II score, history of VTE, need for vasopressors, and end-stage renal disease: sub-hazard ratio (SHR) = 0.92, 95% confidence interval (CI): 0.70-1.21, P-value = 0.56 for the competing risk analysis; hazard ratio (HR) = 0.92, 95% CI: 0.68-1.23, P-value = 0.57 for cause-specific analysis. Dalteparin was associated with a significant reduction in risk of pulmonary embolism (PE): SHR = 0.54, 95% CI: 0.31-0.94, P-value = 0.02 for the competing risk analysis; HR = 0.51, 95% CI: 0.30-0.88, P-value = 0.01 for the cause-specific analysis. Two additional sensitivity analyses using the treatment variable as a time-dependent covariate and using as-treated and per-protocol approaches demonstrated similar findings.This competing risk analysis yields no significant treatment effect on PLDVT but a superior effect of dalteparin on PE compared with UFH in medical-surgical critically ill patients. The findings from the competing risk method are in accordance with results from the cause-specific analysis.clinicaltrials.gov Identifier: NCT00182143.
Medicine 09/2015; 94(36):e1479. DOI:10.1097/MD.0000000000001479 · 5.72 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: background: While a number of pharmacological interventions exist for the treatment of opioid use disorder, evidence evaluating the effect of pain on substance use behavior, attrition rate, and physical or mental health among these therapies has not been well established. We aim to evaluate these effects using evidence gathered from a systematic review of studies evaluating chronic non-cancer pain (CNCP) in patients with opioid use disorder. Methods: We searched the Medline, EMBASE, PubMed, PsycINFO, Web of Science, Cochrane Database of Systematic Reviews, ProQuest Disser- tations and theses Database, Cochrane Central Register of Controlled Trials, World Health Organization International Clinical Trials Registry Platform Search Portal, and National Institutes for Health Clinical Trials Registry databases to identify articles evaluating the impact of pain on addiction treatment outcomes for patients maintained on opioid agonist therapy.
results: Upon screening 3,540 articles, 14 studies with a combined sample of 3,128 patients fulfilled the review inclusion criteria. Results from the meta-analysis suggest that pain has no effect on illicit opioid consumption [pooled odds ratio (pOR): 0.70, 95%CI 0.41–1.17; I2 = 0.0] but a protective effect for reducing illicit non-opioid substance use (pOR: 0.57, 95%CI 0.41–0.79; I2 = 0.0). Studies evaluating illicit opioid consumption using other measures demonstrate pain to increase the risk for opioid abuse. Pain is significantly associated with the presence of psychiatric disorders (pOR: 2.18; 95%CI 1.6, 2.9; I2 = 0.0%).
conclusIon: CNCP may increase risk for continued opioid abuse and poor psychiatric functioning. Qualitative synthesis of the findings suggests that major methodological differences in the design and measurement of pain and treatment response outcomes are likely impacting the effect estimates.
Substance Abuse: Research and Treatment 09/2015; 9:59-80. DOI:10.4137/SaRt.S30120.
[Show abstract][Hide abstract] ABSTRACT: Background and Purpose—Central poststroke pain is a chronic neuropathic disorder that follows a stroke. Current research on its management is limited, and no review has evaluated all therapies for central poststroke pain.
Methods—We conducted a systematic review of randomized controlled trials to evaluate therapies for central poststroke
pain. We identified eligible trials, in any language, by systematic searches of AMED, CENTRAL, CINAHL, DARE,
EMBASE, HealthSTAR, MEDLINE, and PsychINFO. Eligible trials (1) enrolled ≥10 patients with central poststroke pain; (2) randomly assigned them to an active therapy or a control arm; and (3) collected outcome data ≥14 days after treatment. Pairs of reviewers, independently and in duplicate, screened titles and abstracts of identified citations, reviewed full texts of potentially eligible trials, and extracted information from eligible studies. We used a modified Cochrane tool to evaluate risk of bias of eligible studies, and collected patient-important outcomes according to recommendations by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials. We conducted, when possible, random effects meta-analyses, and evaluated our certainty in treatment effects using the Grading of Recommendations Assessment, Development, and Evaluation System.
Results—Eight eligible English language randomized controlled trials (459 patients) tested anticonvulsants, an antidepressant, an opioid antagonist, repetitive transcranial magnetic stimulation, and acupuncture. Results suggested that all therapies had little to no effect on pain and other patient-important outcomes. Our certainty in the treatment estimates ranged from very low to low.
Conclusions—Our findings are inconsistent with major clinical practice guidelines; the available evidence suggests no beneficial effects of any therapies that researchers have evaluated in randomized controlled trials.
[Show abstract][Hide abstract] ABSTRACT: Introduction:
Multiple early warning scores (EWS) have been developed and implemented to reduce cardiac arrests on hospital wards. Case-control observational studies that generate an area under the receiver operator curve (AUROC) are the usual validation method, but investigators have also generated EWS with algorithms with no prior clinical knowledge. We present a protocol for the validation and comparison of our local Hamilton Early Warning Score (HEWS) with that generated using decision tree (DT) methods.
Methods and analysis:
A database of electronically recorded vital signs from 4 medical and 4 surgical wards will be used to generate DT EWS (DT-HEWS). A third EWS will be generated using ensemble-based methods. Missing data will be multiple imputed. For a relative risk reduction of 50% in our composite outcome (cardiac or respiratory arrest, unanticipated intensive care unit (ICU) admission or hospital death) with a power of 80%, we calculated a sample size of 17 151 patient days based on our cardiac arrest rates in 2012. The performance of the National EWS, DT-HEWS and the ensemble EWS will be compared using AUROC.
Ethics and dissemination:
Ethics approval was received from the Hamilton Integrated Research Ethics Board (#13-724-C). The vital signs and associated outcomes are stored in a database on our secure hospital server. Preliminary dissemination of this protocol was presented in abstract form at an international critical care meeting. Final results of this analysis will be used to improve on the existing HEWS and will be shared through publication and presentation at critical care meetings.
BMJ Open 09/2015; 5(9):e008699. DOI:10.1136/bmjopen-2015-008699 · 2.27 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Knowledge translation (KT) involves implementation of evidence-based strategies and guidelines into practice to improve the process of care and health outcomes for patients. Findings from pragmatic trials may be used in KT to provide patients, healthcare providers and policymakers with information to optimize healthcare decisions based on how a given strategy or intervention performs under the real world conditions. However, pragmatic trials have been criticized for having the following problems: i) high rates of loss to follow-up; ii) nonadherence to study intervention; iii) unblinded treatment and patient self-assessment, which can potentially create bias; iv) being less perfect experiments than efficacy trials; v) sacrificing internal validity to achieve generalizability; and vi) often requiring large sample sizes to detect small treatment effects in heterogeneous populations. In this paper, we discuss whether these criticisms hold merit, or if they are simply driven by confusion about the purpose of pragmatic trials. We use the Cardiovascular Health Awareness Program (CHAP) trial - a community randomized pragmatic trial designed to assess whether offering a highly organized, community-based CHAP intervention compared to usual care can reduce cardiovascular disease-related outcomes - to address these specific criticisms and illustrate how to reduce this confusion.
Current controlled trials ISRCTN50550004 (9 May 2007).
[Show abstract][Hide abstract] ABSTRACT: Background and Purpose: While advances in technology and health have increased the life expectancy of young adults (YA) with life limiting conditions (LLC), health and social services to support their complex needs and realization of their goals lag behind. This paper is one of the first descriptions of the barriers in health, education and social service systems (HESS) from the perspective of YA’s. Further, this presentation will exemplify the family and community resources that influence their transition experience.
Methods: A descriptive case study was used to examine the factors that affect the transition process. A purposeful sample of 10 young adults and 4 expert consultants was selected. Face to face interviews and innovative online bulletin board focus groups provided accessibility to this geographically dispersed and medically fragile population with divergent communication abilities. Conventional and directed content analyses were used.
Results: Decreasing supports from HESS, changing and declining health, uncertainty about the future, and isolation are among the factors that increase the YA’s vulnerability at transition. While some participants demonstrated a striking capacity to navigate system barriers, others “got stuck”. Some participants transformed their vulnerability into opportunity through family and community support, and their perception of the imposed transitional changes as a challenge rather than a threat. Further, the creative and time consuming work the young adults, their families and communities have undertaken to overcome system barriers and initiate changes demonstrate opportunities for improvements in HESS practice and policy. Descriptions and illustrations of the varied transition experiences and outcomes will be presented.
Conclusions: Opportunities for connectivity with their peers, and integrated services infused with palliative philosophies will improve quality of life for YA’s and support for their families. Contributions to research and practice include the exploration of the experience of young adults with LLC, and an original contribution to community and family impact on appraisal of stress.
International Family Nursing Association, Odense, Denmark; 08/2015
[Show abstract][Hide abstract] ABSTRACT: Background: Hemodialysis patients are often advised not to shower if they have a central ve-nous catheter (catheter). We developed a shower technique catheter protocol for hemodialysis patients with healed catheter exit sites, designed to permit showering but not increase catheter-related infection risk. Research question: Is it feasible to conduct a randomized control trial comparing the rate of catheter related bacteremia in adult satellite hemodialysis patients using the shower technique protocol versus standard catheter care alone with 6 month follow up? Study Design: This pilot study is a multi-centre randomized control trial. Eligible participants will be randomized to shower technique protocol versus standard care after meeting predefined criteria to confirm healed tunneled catheter exit site. Primary Outcome: Feasibility will be determined by 5 outcome measures: 1) accuracy of the catheter related bacteremia rate documentation in the satellite hemodialysis centre setting, percentage of patients 2) screened, 3) recruited, 4) educated successfully in the shower technique protocol (intervention arm), and 5) treatment contamination of study groups. Study Setting: In 2 academic and 3 community based satellite hemodialysis centres in south central Ontario, Canada. Patient Population: Adult satellite hemodialysis patients dialyzing via tunneled central venous catheters with healed catheter exit sites. Intervention: Shower technique protocol and standard catheter care or control (standard cath-eter care only). Analysis: Each measure of feasibility has its own statistical threshold for success. If the threshold is reached in 4 of the 5 measures, the full study will be deemed feasible. Discussion: A pilot feasibility study of the larger study is critical due to the potential challenges associated with recruitment, compliance and participant ascertainment bias.
[Show abstract][Hide abstract] ABSTRACT: Pilot trials are smaller randomized controlled trials conducted to inform the design and assess the feasibility of a large-scale trials. The objectives of this systematic review were to describe pilot trials in pediatric critical care, their conclusions about the clinical implications of the results, and the need for future research and to determine the frequency of large follow-up trials.
The Evidence in Pediatric Intensive Care database (http://epicc.mcmaster.ca), a comprehensive repository of published pediatric critical care randomized controlled trials and the World Health Organization's Clinical Trials Registry Platform.
Randomized controlled trials described in the publication as "pilot," "feasibility," "proof-of-concept," "exploratory," "phase 2," "vanguard," or "preliminary."
Pairs of reviewers screened studies for eligibility and abstracted data independently.
We found 32 pilot trials (12.2% of all pediatric critical care randomized controlled trials) published before July 2014, varying in size from 6 to 165 children. Pilot trials were significantly smaller than those not described as pilots, but other key characteristics were not significantly different. The authors of 16 publications (48.4%) included explicit and specific conclusions about the design or feasibility of larger trials based on the results of the pilot trial. In 20 publications (64.5%), the authors made conclusions about clinical efficacy based on results of the pilot trial. Four of the 32 pilot trials (12.9%) led to larger trials, two of which have been published.
Published pilot trials in pediatric critical care often focus on clinical outcomes. They uncommonly report explicit feasibility outcomes, criteria for success, or rationale for the pilot sample size. These pilot trials infrequently lead to larger trials. Understanding and addressing the reasons for this are key to the success of pediatric critical care research.
Pediatric Critical Care Medicine 06/2015; DOI:10.1097/PCC.0000000000000475 · 2.34 Impact Factor