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1.
Support Care Cancer ; 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32002617

RESUMO

PURPOSE: Trastuzumab-based chemotherapy is usually administered through either a peripherally inserted central catheter (PICC) or a totally implanted vascular access device (PORT). As the most effective type of access is unknown, a feasibility trial, prior to conducting a large pragmatic trial, was undertaken. METHODS: The trial methodology utilized the integrated consent model incorporating oral consent. Patients receiving trastuzumab-based neo/adjuvant chemotherapy for early-stage breast cancer were randomized to a PICC or PORT insertion. Feasibility was reflected through a combination of endpoints; however, the a priori definition of feasibility was > 25% of patients approached agreed to randomization and > 25% of physicians approached patients. Secondary outcomes included rates of line-associated complications such as thrombotic events requiring anticoagulation, line infections or phlebitis. RESULTS: During the study period, 4/15 (26.7%) medical oncologists approached patients about study participation. Of 59 patients approached, 56 (94.9%) agreed to randomization, 29 (51.8%) were randomized to PICC and 27 (48.2%) to PORT access. Overall, 17.2% (5/29) and 14.8% (4/27) of patients had at least one line-associated complication in the PICC and PORT arms respectively. The study was terminated early due to slow accrual. CONCLUSION: The study met its feasibility endpoints with respect to patient and physician engagement. However, the slow rate of accrual (56 patients in 2 years) means that conducting a large pragmatic trial would require additional strategies to make such a study possible. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02632435.

2.
BMJ Open ; 10(2): e033913, 2020 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-32034026

RESUMO

INTRODUCTION: Acute brain injury is a challenging public health problem worldwide. Elevated intracranial pressure is a common complication after acute brain injury. Hyperosmolar therapy is one of the main therapeutic strategies for the management of intracranial hypertension. This study protocol outlines an umbrella review of meta-analyses which will investigate the benefits and harms of hyperosmolar therapy routinely used for the management of acute brain injury in the intensive care. METHODS AND ANALYSIS: We will search PubMed/MEDLINE, EMBASE and the Cochrane Database of Systematic Reviews. We will include meta-analyses of primary research studies (eg, randomised controlled trials, observational studies or both) that evaluate one or more hyperosmolar solutions (including hypertonic saline and/or mannitol) for the treatment of adult patients with acute brain injury of any severity. Two researchers will independently screen all citations, full-text articles and abstract data. Potential conflicts will be resolved through discussion with a third researcher. Primary outcomes will be mortality and neurological outcomes at discharge. Secondary outcomes will include control of intracranial pressure, cerebral perfusion pressure, length of stay (in hospital an intensive care unit) and any adverse event. Quality of the included meta-analyses will be assessed using the AMSTAR-2 tool. An overall summary of methods and results will be performed using tabular and graphical approaches and will be supplemented by narrative description. We will analyse whether published meta-analyses present an outline of available evidence (eg, cited, described and discussed any previous meta-analysis). Where objectives from two or more meta-analyses overlap, we will assess the causes of any noted discrepancies between meta-analyses. ETHICS AND DISSEMINATION: No ethical approval will be required. Findings from this study will be published in a peer-reviewed journal. All data will be deposited in a cross-disciplinary public repository. PROSPERO REGISTRATION NUMBER: CRD42019148152.

3.
BMJ Open ; 10(2): e034463, 2020 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-32060160

RESUMO

INTRODUCTION: There has been a growing awareness of the need for rigorously and transparent reported health research, to ensure the reproducibility of studies by future researchers. Health economic evaluations, the comparative analysis of alternative interventions in terms of their costs and consequences, have been promoted as an important tool to inform decision-making. The objective of this study will be to investigate the extent to which articles of economic evaluations of healthcare interventions indexed in MEDLINE incorporate research practices that promote transparency, openness and reproducibility. METHODS AND ANALYSIS: This is the study protocol for a cross-sectional comparative analysis. We registered the study protocol within the Open Science Framework (osf.io/gzaxr). We will evaluate a random sample of 600 cost-effectiveness analysis publications, a specific form of health economic evaluations, indexed in MEDLINE during 2012 (n=200), 2019 (n=200) and 2022 (n=200). We will include published papers written in English reporting an incremental cost-effectiveness ratio in terms of costs per life years gained, quality-adjusted life years and/or disability-adjusted life years. Screening and selection of articles will be conducted by at least two researchers. Reproducible research practices, openness and transparency in each article will be extracted using a standardised data extraction form by multiple researchers, with a 33% random sample (n=200) extracted in duplicate. Information on general, methodological and reproducibility items will be reported, stratified by year, citation of the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement and journal. Risk ratios with 95% CIs will be calculated to represent changes in reporting between 2012-2019 and 2019-2022. ETHICS AND DISSEMINATION: Due to the nature of the proposed study, no ethical approval will be required. All data will be deposited in a cross-disciplinary public repository. It is anticipated the study findings could be relevant to a variety of audiences. Study findings will be disseminated at scientific conferences and published in peer-reviewed journals.

4.
Trials ; 21(1): 30, 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31907000

RESUMO

BACKGROUND: Given the complex nature of opioid addiction treatment and the rising number of available opioid substitution and antagonist therapies (OSAT), there is no 'gold standard' measure of treatment effectiveness, and each successive trial measures a different set of outcomes which reflect success in arbitrary or opportune terms. We sought to describe the variation in current outcomes employed across clinical trials for opioid addiction, as well as determine whether a discrepancy exists between the treatment targets that patients consider important and how treatment effectiveness is measured in the literature. METHODS: We searched nine commonly used databases (e.g., EMBASE, MEDLINE) from inception to August 1, 2015. Outcomes used across trials were extracted and categorized according to previously established domains. To evaluate patient-reported goals of treatment, semi-structured interviews were conducted with 18 adults undergoing methadone treatment. RESULTS: We identified 60 trials eligible for inclusion. Once outcomes were categorized into eight broad domains (e.g., abstinence/substance abuse), we identified 21 specific outcomes with furthermore 53 subdomains and 118 measurements. Continued opioid use and treatment retention were the most commonly reported measures (46%, n = 28). The majority of patients agreed that abstinence from opioids was a primary goal in their treatment, although they also stressed goals under-reported in clinical trials. CONCLUSIONS: There is inconsistency in the measures used to evaluate the effectiveness of OSATs. Individual and population level decision making is being guided by a standard of effect considered useful to researchers yet in direct conflict with what patients deem important. TRIAL REGISTRATION: PROSPERO, CRD42013006507.

5.
Trials ; 21(1): 34, 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31910857

RESUMO

BACKGROUND: Randomised controlled trials (RCTs) provide the most reliable information to inform clinical practice and patient care. We aimed to map global clinical research publication activity through RCT-related articles in high-impact-factor medical journals over the past five decades. METHODS: We conducted a cross-sectional analysis of articles published in the highest ranked medical journals with an impact factor > 10 (according to Journal Citation Reports published in 2017). We searched PubMed/MEDLINE (from inception to December 31, 2017) for all RCT-related articles (e.g. primary RCTs, secondary analyses and methodology papers) published in high-impact-factor medical journals. For each included article, raw metadata were abstracted from the Web of Science. A process of standardization was conducted to unify the different terms and grammatical variants and to remove typographical, transcription and/or indexing errors. Descriptive analyses were conducted (including the number of articles, citations, most prolific authors, countries, journals, funding sources and keywords). Network analyses of collaborations between countries and co-words are presented. RESULTS: We included 39,305 articles (for the period 1965-2017) published in forty journals. The Lancet (n = 3593; 9.1%), the Journal of Clinical Oncology (n = 3343; 8.5%) and The New England Journal of Medicine (n = 3275 articles; 8.3%) published the largest number of RCTs. A total of 154 countries were involved in the production of articles. The global productivity ranking was led by the United States (n = 18,393 articles), followed by the United Kingdom (n = 8028 articles), Canada (n = 4548 articles) and Germany (n = 4415 articles). Seventeen authors who had published 100 or more articles were identified; the most prolific authors were affiliated with Duke University (United States), Harvard University (United States) and McMaster University (Canada). The main funding institutions were the National Institutes of Health (United States), Hoffmann-La Roche (Switzerland), Pfizer (United States), Merck Sharp & Dohme (United States) and Novartis (Switzerland). The 100 most cited RCTs were published in nine journals, led by The New England Journal of Medicine (n = 78 articles), The Lancet (n = 9 articles) and JAMA (n = 7 articles). These landmark contributions focused on novel methodological approaches (e.g. the "Bland-Altman method") and trials on the management of chronic conditions (e.g. diabetes control, hormone replacement therapy in postmenopausal women, multiple therapies for diverse cancers, cardiovascular therapies such as lipid-lowering statins, antihypertensive medications, and antiplatelet and antithrombotic therapy). CONCLUSIONS: Our analysis identified authors, countries, funding institutions, landmark contributions and high-impact-factor medical journals publishing RCTs. Over the last 50 years, publication production in leading medical journals has increased, with Western countries leading in research but with low- and middle-income countries showing very limited representation.

6.
Syst Rev ; 9(1): 20, 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-31996261

RESUMO

BACKGROUND: Two reviews and an overview were produced for the Canadian Task Force on Preventive Health Care guideline on screening for esophageal adenocarcinoma in patients with chronic gastroesophageal reflux disease (GERD) without alarm symptoms. The goal was to systematically review three key questions (KQs): (1) The effectiveness of screening for these conditions; (2) How adults with chronic GERD weigh the benefits and harms of screening, and what factors contribute to their preferences and decision to undergo screening; and (3) Treatment options for Barrett's esophagus (BE), dysplasia or stage 1 EAC (overview of reviews). METHODS: Bibliographic databases (e.g. Ovid MEDLINE®) were searched for each review in October 2018. We also searched for unpublished literature (e.g. relevant websites). The liberal accelerated approach was used for title and abstract screening. Two reviewers independently screened full-text articles. Data extraction and risk of bias assessments were completed by one reviewer and verified by another reviewer (KQ1 and 2). Quality assessments were completed by two reviewers independently in duplicate (KQ3). Disagreements were resolved through discussion. We used various risk of bias tools suitable for study design. The GRADE framework was used for rating the certainty of the evidence. RESULTS: Ten studies evaluated the effectiveness of screening. One retrospective study reported no difference in long-term survival (approximately 6 to 12 years) between those who had a prior esophagogastroduodenoscopy and those who had not (adjusted HR 0.93, 95% confidence interval (CI) 0.58-1.50). Though there may be higher odds of a stage 1 diagnosis than a more advanced diagnosis (stage 2-4) if an EGD had been performed in the previous 5 years (OR 2.27, 95% CI 1.00-7.67). Seven studies compared different screening modalities, and showed little difference between modalities. Three studies reported on patients' unwillingness to be screened (e.g. due to anxiety, fear of gagging). Eleven systematic reviews evaluated treatment modalities, providing some evidence of early treatment effect for some outcomes. CONCLUSIONS: Little evidence exists on the effectiveness of screening and values and preferences to screening. Many treatment modalities have been evaluated, but studies are small. Overall, there is uncertainty in understanding the effectiveness of screening and early treatments. SYSTEMATIC REVIEW REGISTRATIONS: PROSPERO (CRD42017049993 [KQ1], CRD42017050014 [KQ2], CRD42018084825 [KQ3]).

7.
Orphanet J Rare Dis ; 15(1): 12, 2020 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-31937333

RESUMO

BACKGROUND: Inherited metabolic diseases (IMDs) are a group of individually rare single-gene diseases. For many IMDs, there is a paucity of high-quality evidence that evaluates the effectiveness of clinical interventions. Clinical effectiveness trials of IMD interventions could be supported through the development of core outcome sets (COSs), a recommended minimum set of standardized, high-quality outcomes and associated outcome measurement instruments to be incorporated by all trials in an area of study. We began the process of establishing pediatric COSs for two IMDs, medium-chain acyl-CoA dehydrogenase (MCAD) deficiency and phenylketonuria (PKU), by reviewing published literature to describe outcomes reported by authors, identify heterogeneity in outcomes across studies, and assemble a candidate list of outcomes. METHODS: We used a comprehensive search strategy to identify primary studies and guidelines relevant to children with MCAD deficiency and PKU, extracting study characteristics and outcome information from eligible studies including outcome measurement instruments for select outcomes. Informed by an established framework and a previously published pediatric COS, outcomes were grouped into five, mutually-exclusive, a priori core areas: growth and development, life impact, pathophysiological manifestations, resource use, and death. RESULTS: For MCAD deficiency, we identified 83 outcomes from 52 articles. The most frequently represented core area was pathophysiological manifestations, with 33 outcomes reported in 29/52 articles (56%). Death was the most frequently reported outcome. One-third of outcomes were reported by a single study. The most diversely measured outcome was cognition and intelligence/IQ for which eight unique measurement instruments were reported among 14 articles. For PKU, we identified 97 outcomes from 343 articles. The most frequently represented core area was pathophysiological manifestations with 31 outcomes reported in 281/343 articles (82%). Phenylalanine concentration was the most frequently reported outcome. Sixteen percent of outcomes were reported by a single study. Similar to MCAD deficiency, the most diversely measured PKU outcome was cognition and intelligence/IQ with 39 different instruments reported among 82 articles. CONCLUSIONS: Heterogeneity of reported outcomes and outcome measurement instruments across published studies for both MCAD deficiency and PKU highlights the need for COSs for these diseases, to promote the use of meaningful outcomes and facilitate comparisons across studies.

8.
Obes Rev ; 21(3): e12972, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31943650

RESUMO

Multiple clinical practice guidelines (CPGs) have been established for pregnant women with obesity. The quality and consistency of recommendations remain unknown. The objective of this study is to conduct a systematic review to synthesize and appraise evidence from CPGs, available worldwide, for pregnant women affected by obesity. An experienced information specialist performed a rigorous search of the literature, searching MEDLINE, Embase, grey literature, and guideline registries to locate CPGs that reported on pregnancy care relating to obesity. CPGs related to antenatal care of pregnant women with obesity (pre-pregnancy body mass index [BMI] ≥ 30 kg/m2 ) in low-risk (eg, care provider = family physician or midwife) or high-risk settings (eg, obstetrician or maternal fetal medicine) were included. CPGs were appraised for quality with independent data collection by two raters. Information was categorized into five domains: preconception care. care during pregnancy, diet and exercise during pregnancy, care immediately before, during, and after delivery, and postpartum care. The literature search yielded 2614 unique citations. Following screening of abstracts and full texts, 32 CPGs were included, with quality ranging between 0 and 100 on the AGREE II tool. The strongest evidence related to nutritional advice, exercise, and pregnancy risk counselling. Guidance was limited for timing of screening tests, antenatal visits and delivery, ideal postpartum care, and management of adverse pregnancy outcomes. Most guidelines in this population are not evidence based. Research is needed to bridge knowledge gaps pertaining to fetal antenatal surveillance, management of adverse outcomes and postpartum care, and enhance consistency across CPGs.

9.
Stem Cells Transl Med ; 9(2): 158-168, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31746123

RESUMO

Regenerative stem cell-based therapies for bronchopulmonary dysplasia (BPD), the most common preterm birth complication, demonstrate promise in animals. Failure to objectively appraise available preclinical data and identify knowledge gaps could jeopardize clinical translation. We performed a systematic review and network meta-analysis (NMA) of preclinical studies testing cell-based therapies in experimental neonatal lung injury. Fifty-three studies assessing 15 different cell-based therapies were identified: 35 studied the effects of mesenchymal stromal cells (MSCs) almost exclusively in hyperoxic rodent models of BPD. Exploratory NMAs, for select outcomes, suggest that MSCs are the most effective therapy. Although a broad range of promising cell-based therapies has been assessed, few head-to-head comparisons and unclear risk of bias exists. Successful clinical translation of cell-based therapies demands robust preclinical experimental design with appropriately blinded, randomized, and statistically powered studies, based on biological plausibility for a given cell product, in standardized models and endpoints with transparent reporting.

10.
IEEE Trans Med Imaging ; 39(1): 75-86, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31170066

RESUMO

Standard positron emission tomography (PET) reconstruction techniques are based on maximum-likelihood (ML) optimization methods, such as the maximum-likelihood expectation-maximization (MLEM) algorithm and its variations. Most methodologies rely on a positivity constraint on the activity distribution image. Although this constraint is meaningful from a physical point of view, it can be a source of bias for low-count/high-background PET, which can compromise accurate quantification. Existing methods that allow for negative values in the estimated image usually utilize a modified log-likelihood, and therefore break the data statistics. In this paper, we propose to incorporate the positivity constraint on the projections only, by approximating the (penalized) log-likelihood function by an adequate sequence of objective functions that are easily maximized without constraint. This sequence is constructed such that there is hypo-convergence (a type of convergence that allows the convergence of the maximizers under some conditions) to the original log-likelihood, hence allowing us to achieve maximization with positivity constraint on the projections using simple settings. A complete proof of convergence under weak assumptions is given. We provide results of experiments on simulated data where we compare our methodology with the alternative direction method of multipliers (ADMM) method, showing that our algorithm converges to a maximizer, which stays in the desired feasibility set, with faster convergence than ADMM. We also show that this approach reduces the bias, as compared with MLEM images, in necrotic tumors-which are characterized by cold regions surrounded by hot structures-while reconstructing similar activity values in hot regions.

11.
IEEE Trans Med Imaging ; 39(1): 11-22, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31144629

RESUMO

In this study, we explore the use of a spatially-variant penalty strength in penalized image reconstruction using anatomical priors to reduce the dependence of lesion contrast on surrounding activity and lesion location. This work builds on a previous method to make the local perturbation response (LPR) approximately spatially invariant. While the dependence of lesion contrast on the local properties introduced by the anatomical penalty is intentional, the method aims to reduce the influence from surroundings lying along the lines of response (LORs) but not in the penalty neighborhood structure. The method is evaluated using simulated data, assuming that the anatomical information is absent or well-aligned with the corresponding activity images. Since the parallel level sets (PLS) penalty is convex and has shown promising results in the literature, it is chosen as the representative anatomical penalty and incorporated into the previously proposed preconditioned algorithm (L-BFGS-B-PC) for achieving good image quality and fast convergence rate. A 2D disc phantom with a feature at the center and a 3D XCAT thorax phantom with lesions inserted in different slices are used to study how surrounding activity and lesion location affect the visual appearance and quantitative consistency. A bias and noise analysis is also performed with the 2D disc phantom. The consistency of the algorithm convergence rate with respect to different data noise and background levels is also investigated using the XCAT phantom. Finally, an example of reconstruction for a patient dataset with inserted pseudo lesions is used as a demonstration in a clinical context. We show that applying the spatially-variant penalization with PLS can reduce the dependence of the lesion contrast on the surrounding activity and lesion location. It does not affect the bias and noise trade-off curves for matched local resolution. Moreover, when using the proposed penalization, significant improvement in algorithm convergence rate and convergence consistency is observed.

12.
Syst Rev ; 8(1): 320, 2019 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-31823819

RESUMO

BACKGROUND: There has been increased interest in the role of cannabis for treating medical conditions. The availability of different cannabis-based products can make the side effects of exposure unpredictable. We sought to conduct a scoping review of systematic reviews assessing benefits and harms of cannabis-based medicines for any condition. METHODS: A protocol was followed throughout the conduct of this scoping review. A protocol-guided scoping review conduct. Searches of bibliographic databases (e.g., MEDLINE®, Embase, PsycINFO, the Cochrane Library) and gray literature were performed. Two people selected and charted data from systematic reviews. Categorizations emerged during data synthesis. The reporting of results from systematic reviews was performed at a high level appropriate for a scoping review. RESULTS: After screening 1975 citations, 72 systematic reviews were included. The reviews covered many conditions, the most common being pain management. Several reviews focused on management of pain as a symptom of conditions such as multiple sclerosis (MS), injury, and cancer. After pain, the most common symptoms treated were spasticity in MS, movement disturbances, nausea/vomiting, and mental health symptoms. An assessment of review findings lends to the understanding that, although in a small number of reviews results showed a benefit for reducing pain, the analysis approach and reporting in other reviews was sub-optimal, making it difficult to know how consistent findings are when considering pain in general. Adverse effects were reported in most reviews comparing cannabis with placebo (49/59, 83%) and in 20/24 (83%) of the reviews comparing cannabis to active drugs. Minor adverse effects (e.g., drowsiness, dizziness) were common and reported in over half of the reviews. Serious harms were not as common, but were reported in 21/59 (36%) reviews that reported on adverse effects. Overall, safety data was generally reported study-by-study, with few reviews synthesizing data. Only one review was rated as high quality, while the remaining were rated of moderate (n = 36) or low/critically low (n = 35) quality. CONCLUSIONS: Results from the included reviews were mixed, with most reporting an inability to draw conclusions due to inconsistent findings and a lack of rigorous evidence. Mild harms were frequently reported, and it is possible the harms of cannabis-based medicines may outweigh benefits. SYSTEMATIC REVIEW REGISTRATION: The protocol for this scoping review was posted in the Open Access (https://ruor.uottawa.ca/handle/10393/37247).

13.
Med Phys ; 2019 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-31794071

RESUMO

Positron emission tomography/magnetic resonance imaging (PET/MRI) potentially offers several advantages over positron emission tomography/computed tomography (PET/CT), for example, no CT radiation dose and soft tissue images from MR acquired at the same time as the PET. However, obtaining accurate linear attenuation correction (LAC) factors for the lung remains difficult in PET/MRI. LACs depend on electron density and in the lung, these vary significantly both within an individual and from person to person. Current commercial practice is to use a single-valued population-based lung LAC, and better estimation is needed to improve quantification. Given the under-appreciation of lung attenuation estimation as an issue, the inaccuracy of PET quantification due to the use of single-valued lung LACs, the unique challenges of lung estimation, and the emerging status of PET/MRI scanners in lung disease, a review is timely. This paper highlights past and present methods, categorizing them into segmentation, atlas/mapping, and emission-based schemes. Potential strategies for future developments are also presented.

14.
Sci Rep ; 9(1): 19582, 2019 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-31862905

RESUMO

We performed a network meta-analysis of randomised controlled trials (RCTs) and non-randomised studies in adult peritoneal dialysis patients to evaluate the effects of specific renin-angiotensin aldosterone systems (RAAS) blockade classes on residual kidney function and peritoneal membrane function. Key outcome parameters included the following: residual glomerular filtration rate (rGFR), urine volume, anuria, dialysate-to-plasma creatinine ratio (D/P Cr), and acceptability of treatment. Indirect treatment effects were compared using random-effects model. Pooled standardised mean differences (SMDs) and odd ratios (ORs) were estimated with 95% confidence intervals (CIs). We identified 10 RCTs (n = 484) and 10 non-randomised studies (n = 3,305). Regarding changes in rGFR, RAAS blockade with angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) were more efficacious than active control (SMD 0.55 [0.06-1.04] and 0.62 [0.19-1.04], respectively) with the protective effect on rGFR observed only after usage ≥12 months, and no differences among ACEIs and ARBs. Compared with active control, only ACEIs showed a significantly decreased risk of anuria (OR 0.62 [0.41-0.95]). No difference among treatments for urine volume and acceptability of treatment were observed, whereas evidence for D/P Cr is inconclusive. The small number of randomised studies and differences in outcome definitions used may limit the quality of the evidence.

15.
BMJ Open ; 9(11): e027451, 2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31694842

RESUMO

OBJECTIVES: We systematically reviewed the literature to identify evidence-informed recommendations regarding the detection of drug-induced pancreatitis (DIP) and, secondarily, to describe clinical processes for the diagnosis of DIP. DESIGN: Systematic review. DATA SOURCES: Ovid MEDLINE, including Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Embase Classic+Embase, the Cochrane Library. ELIGIBILITY CRITERIA: We included clinical practice guidelines, systematic reviews, narrative reviews and observational studies with a focus of establishing incidence, prevalence or diagnostic approaches for DIP. Clinical trials that diagnosed DIP as an outcome were also included. DATA EXTRACTION AND SYNTHESIS: Two reviewers screened citations and performed data extraction. A narrative synthesis of the evidence was prepared. RESULTS: Fifty-nine studies were included. Early published evidence suggested serial pancreatic ultrasound could detect subclinical pancreatitis; however, subsequent studies demonstrated no utility of serial ultrasound or serial monitoring of pancreatic enzymes in the early detection of DIP. Two small studies conducted in patients with a high baseline risk of acute pancreatitis concluded serial monitoring of pancreatic enzymes may be useful to guide early discontinuation of medications with known associations with pancreatitis. Early discontinuation of medication was not advised for lower-risk patients because some medications cause transient elevations of pancreatic enzymes that do not progress to acute pancreatitis. Eight of 52 studies (15%) reporting a clinical diagnostic process for DIP reported using currently accepted criteria for the diagnosis of acute pancreatitis. A variety of methods were used to assess drug-related causality. CONCLUSIONS: There is minimal evidence to support the use of serial monitoring by ultrasound or pancreatic enzymes to detect cases of DIP. Serial monitoring may be useful to guide early discontinuation of DIP-associated drugs in high-risk patients, but not in lower-risk patients. Greater uptake of standardised diagnostic and causality criteria for DIP is needed. TRIAL REGISTRATION NUMBER: CRD42017060473.

16.
Transl Stroke Res ; 2019 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-31654281

RESUMO

There may be the potential to improve stroke recovery with mesenchymal stem cells (MSCs); however, questions about the efficacy and safety of this treatment remain. To address these issues and inform future studies, we performed a preclinical and clinical systematic review of MSC therapy for subacute and chronic ischemic stroke. MEDLINE, Embase, the Cochrane Register of Controlled Trials, and PubMed were searched. For the clinical review, interventional and observational studies of MSC therapy in ischemic stroke patients were included. For the preclinical review, interventional studies of MSC therapy using in vivo animal models of subacute or chronic stroke were included. Measures of safety and efficacy were assessed. Eleven clinical and 76 preclinical studies were included. Preclinically, MSC therapy was associated with significant benefits for multiple measures of motor and neurological function. Clinically, MSC therapy appeared to be safe, with no increase in adverse events reported (with the exception of self-limited fever immediately following injection). However, the efficacy of treatment was less apparent, with significant heterogeneity in both study design and effect size being observed. Additionally, in the only randomized phase II study to date, efficacy of MSC therapy was not observed. Preclinically, MSC therapy demonstrated considerable efficacy. Although MSC therapy demonstrated safety in the clinical setting, efficacy has yet to be determined. Future studies will need to address the discordance in the continuity of evidence as MSC therapy has been translated from "bench-to-bedside".

17.
Syst Rev ; 8(1): 245, 2019 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-31661033

RESUMO

BACKGROUND: The optimal duration of anticoagulation after a first unprovoked venous thromboembolism (VTE) remains controversial. Deciding to stop or continue anticoagulant therapy indefinitely after completing 3 to 6 months of initial treatment requires balancing the long-term risk of recurrent VTE if anticoagulation is stopped against the long-term risk of major bleeding if anticoagulation is continued. However, knowledge of the long-term risk for major bleeding events during extended anticoagulation in this patient population is limited. We plan to conduct a systematic review and meta-analysis to quantify the risk for major bleeding events during extended oral anticoagulation in patients with first unprovoked VTE. METHODS: Electronic databases including MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials will be systematically searched with the assistance of an information specialist (from inception to March 1, 2019) to identify randomized controlled trials and prospective cohort studies reporting major bleeding during extended oral anticoagulation in patients with first unprovoked VTE, who have completed at least 3 months of initial anticoagulant therapy. Study selection, risk of bias assessment, and data extraction will be performed independently by at least two investigators. The number of major bleeding events and person-years of follow-up will be used to calculate the rate (events per 100 person-years) with its 95% confidence interval for each study cohort, during clinically relevant time periods of extended anticoagulant therapy. Results will be pooled using random effect meta-analysis. DISCUSSION: The planned systematic review and meta-analysis will provide reliable estimates of the risk for major bleeding events during extended anticoagulation. This information will help inform patient prognosis and assist clinicians with balancing the risks and benefits of treatment to guide management of unprovoked VTE. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019128597 .

18.
Phys Med Biol ; 64(20): 205010, 2019 10 16.
Artigo em Inglês | MEDLINE | ID: mdl-31539891

RESUMO

The impact of positron range on PET image reconstruction has often been investigated as a blurring effect that can be partly corrected by adding an element to the PET system matrix in the reconstruction, usually based on a Gaussian kernel constructed from the attenuation values. However, the physics involved in PET is more complex. In regions where density does not vary, positron range indeed involves mainly blurring. However, in more heterogeneous media it can cause other effects. This work focuses on positron range in the lungs and its impact on quantification, especially in the case of pathologies such as cancer or pulmonary fibrosis, for which the lungs have localised varying density. Using Monte Carlo simulations, we evaluate the effects of positron range for multiple radionuclides (18F, 15O, 68Ga, 89Zr, 82Rb, 64Cu and 124I) as, for novel radiotracers, the choice of the labelling radionuclide is important. The results demonstrate quantification biases in highly heterogeneous media, where the measured uptake of high-density regions can be increased by the neighbouring radioactivity from regions of lower density, with the effect more noticeable for radionuclides with high-energy positron emission. When the low-density regions are considered to have less radioactive uptake (e.g. due to the presence of air), the effect is less severe.

19.
PLoS One ; 14(9): e0221713, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31498809

RESUMO

BACKGROUND: Hearing loss is one of the leading causes of disability worldwide. Patients with hearing loss experience impaired quality of life, as well as emotional and financial consequences that affect both themselves and their families. Idiopathic sudden sensorineural hearing loss (ISSNHL) is a common but difficult to treat condition that has a sudden onset of ≤ 72 hour associated with various etiologies, with the majority of cases being idiopathic. There exists a wide range of therapeutic options, however, the uncertainty surrounding their comparative efficacy and safety makes selection of treatment difficult. This systematic review and network meta-analysis (NMA) assessed the relative effects of competing treatments for management of ISSNHL. METHODS: A protocol for this review was registered with PROSPERO (CRD42017073756). A detailed search of MEDLINE, Embase and the Cochrane Library from inception to February 8th, 2018 was carried out by an experienced information specialist. Grey literature was also searched. Screening full-text records, and risk of bias assessment were carried out independently by two reviewers, and disagreements were resolved through consensus or third party adjudication, while data was collected by one reviewer and verified by a second reviewer. Bayesian network meta-analyses (NMA) were performed to inform comparisons between interventions for a priori specified outcomes that included pure tone average (PTA) improvement and hearing recovery. RESULTS: The search identified a total of 1,138 citations, of which 613 remained for review after removal of duplicates. Of these, 23 publications describing 19 unique studies (total sample size of 1,527) met our a priori eligibility criteria, that were assessed to be at unclear or high risk of bias on several domains. We identified data on several interventions for ISSNHL therapy and were able to construct treatment networks consisting of six intervention groups that included placebo; intratympanic (IT) steroid; IT plus systemic steroid; per oral (PO) steroid; intravenous (IV) steroid; and IV plus PO steroid for our NMAs. IT plus systemic steroids demonstrated the largest difference in PTA improvement compared to placebo (25.85 dB, 95% CrI 7.18-40.58), followed by IV plus PO steroids (22.06 dB, 95% CrI 1.24-39.17), IT steroids (18.24 dB, 95% CrI 3.00-29.81). We observed that the difference of PTA improvement between each intervention and placebo diminished over time, attributed to spontaneous recovery. The binary outcomes of hearing recovery demonstrated similar relative ordering of interventions but were less sensitive than PTA improvement to capture the significant differences between interventions and placebo. CONCLUSION: Unclear to high risk of bias trials rated IT plus systemic steroid treatment as the best among the six interventions compared, and all active treatments were better than placebo in improving PTA. However, it should be noted that certain comparisons were based on indirect evidence only or few studies of small sample size, and analyses were unable to control for steroid type and dosage. Given these limitations, further data originating from methodologically sound and rigorous trials with adequate reporting are needed to confirm our findings.

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