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BMJ (Clinical Research Ed.) Aug 2010To study how composite outcomes, which have combined several components into a single measure, are defined, reported, and interpreted. (Review)
Review
OBJECTIVE
To study how composite outcomes, which have combined several components into a single measure, are defined, reported, and interpreted.
DESIGN
Systematic review of parallel group randomised clinical trials published in 2008 reporting a binary composite outcome. Two independent observers extracted the data using a standardised data sheet, and two other observers, blinded to the results, selected the most important component.
RESULTS
Of 40 included trials, 29 (73%) were about cardiovascular topics and 24 (60%) were entirely or partly industry funded. Composite outcomes had a median of three components (range 2-9). Death or cardiovascular death was the most important component in 33 trials (83%). Only one trial provided a good rationale for the choice of components. We judged that the components were not of similar importance in 28 trials (70%); in 20 of these, death was combined with hospital admission. Other major problems were change in the definition of the composite outcome between the abstract, methods, and results sections (13 trials); missing, ambiguous, or uninterpretable data (9 trials); and post hoc construction of composite outcomes (4 trials). Only 24 trials (60%) provided reliable estimates for both the composite and its components, and only six trials (15%) had components of similar, or possibly similar, clinical importance and provided reliable estimates. In 11 of 16 trials with a statistically significant composite, the abstract conclusion falsely implied that the effect applied also to the most important component.
CONCLUSIONS
The use of composite outcomes in trials is problematic. Components are often unreasonably combined, inconsistently defined, and inadequately reported. These problems will leave many readers confused, often with an exaggerated perception of how well interventions work.
Topics: Data Interpretation, Statistical; Randomized Controlled Trials as Topic; Research Design; Treatment Outcome
PubMed: 20719825
DOI: 10.1136/bmj.c3920 -
Frontiers in Pharmacology 2014The use of opioids has been increasing in operating room and intensive care unit to provide perioperative analgesia as well as stable hemodynamics. However, many authors... (Review)
Review
INTRODUCTION
The use of opioids has been increasing in operating room and intensive care unit to provide perioperative analgesia as well as stable hemodynamics. However, many authors have suggested that the use of opioids is associated with the expression of acute opioid tolerance (AOT) and opioid-induced hyperalgesia (OIH) in experimental studies and clinical observations in dose and/or time dependent exposure even when used within the clinically accepted doses. Recently, remifentanil has been used for pain management during anesthesia as well as in the intensive care units because of its rapid onset and offset.
OBJECTIVES
Search of the available literature to assess remifentanil AOT and OIH based on available published data.
METHODS
We reviewed articles analyzing remifentanil AOT and OIH, and focused our literature search on evidence based information. Experimental and clinical studies were identified using electronic searches of Medline (PubMed, Ovid, Springer, and Elsevier, ClinicalKey).
RESULTS
Our results showed that the development of remifentanil AOT and OIH is a clinically significant phenomenon requiring further research.
DISCUSSIONS AND CONCLUSIONS
AOT - defined as an increase in the required opioid dose to maintain adequate analgesia, and OIH - defined as decreased pain threshold after chronic opioid treatment, should be suspected with any unexplained pain report unassociated with the disease progression. The clinical significance of these findings was evaluated taking into account multiple methodological issues including the dose and duration of opioids administration, the different infusion mode, the co-administrated anesthetic drug's effect, method assessing pain sensitivity, and the repetitive and potentially tissue damaging nature of the stimuli used to determine the threshold during opioid infusion. Future studies need to investigate the contribution of remifentanil induced hyperalgesia to chronic pain and the role of pharmacological modulation to reverse this process.
PubMed: 24847273
DOI: 10.3389/fphar.2014.00108 -
Environment International Dec 2018We performed a systematic review of the epidemiology literature to identify the male reproductive effects associated with phthalate exposure. (Review)
Review
OBJECTIVE
We performed a systematic review of the epidemiology literature to identify the male reproductive effects associated with phthalate exposure.
DATA SOURCES AND STUDY ELIGIBILITY CRITERIA
Six phthalates were included in the review: di(2-ethylhexyl) phthalate (DEHP), diisononyl phthalate (DINP), dibutyl phthalate (DBP), diisobutyl phthalate (DIBP), butyl benzyl phthalate (BBP), and diethyl phthalate (DEP). The initial literature search (of PubMed, Web of Science, and Toxline) included all studies of male reproductive effects in humans, and outcomes were selected for full systematic review based on data availability.
STUDY EVALUATION AND SYNTHESIS METHODS
For each outcome, studies were evaluated using criteria defined a priori for risk of bias and sensitivity by two reviewers using a domain-based approach. Evidence was synthesized by outcome and phthalate and strength of evidence was summarized using a structured framework.
RESULTS
The primary outcomes reviewed here are (number of included/excluded studies in parentheses): anogenital distance (6/1), semen parameters (15/9), time to pregnancy (3/5), testosterone (13/8), timing of pubertal development (5/15), and hypospadias/cryptorchidism (4/10). Looking at the overall hazard, there was robust evidence of an association between DEHP and DBP exposure and male reproductive outcomes; this was based primarily on studies of anogenital distance, semen parameters, and testosterone for DEHP and semen parameters and time to pregnancy for DBP. There was moderate evidence of an association between DINP and BBP exposure and male reproductive outcomes based on testosterone and semen parameters for DINP and semen parameters and time to pregnancy for BBP. DIBP and DEP were considered to have slight evidence of an association. For DIBP, the less conclusive evidence was attributed to a more limited literature base (i.e., fewer studies) and lower exposure levels in the population, decreasing the ability to observe an effect. For DEP, the findings were consistent with experimental animal data that suggest DEP does not haves as strong an anti-androgenic effect as other phthalates.
CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS
Overall, despite some inconsistencies across phthalates in the specific outcomes associated with exposure, these results support that phthalate exposure at levels seen in human populations may have male reproductive effects, particularly DEHP and DBP. The relative strength of the evidence reflects differing levels of toxicity as well as differences in the range of exposures studied and the number of available studies. The views expressed are those of the authors and do not necessarily represent the views or policies of the U.S. EPA.
Topics: Environmental Exposure; Humans; Male; Phthalic Acids; Reproduction; Semen; Testosterone
PubMed: 30336412
DOI: 10.1016/j.envint.2018.07.029 -
Experimental Dermatology Apr 2022Pyoderma gangrenosum is a painful recurrent ulcerative neutrophilic dermatosis in which the pathogenesis is incompletely defined. Current evidence suggests that PG is... (Review)
Review
Pyoderma gangrenosum is a painful recurrent ulcerative neutrophilic dermatosis in which the pathogenesis is incompletely defined. Current evidence suggests that PG is associated with dysregulation of components of both the innate and adaptive immune system with dysregulation of neutrophil function and contribution of the Th17 immune axis. PG can be present in numerous heterogeneous clinical presentations and be associated with multiple inflammatory conditions including rheumatoid arthritis, inflammatory bowel disease and hidradenitis suppurativa. However, no critical evaluation of the observed molecular characteristics in PG studies in association with their clinical findings has been assessed. Additionally, emerging evidence suggests a potential role for other cell types and immune pathways including B cells, macrophages, autoantibodies and the complement system in PG, although these have not yet been integrated into the pathogenesis of disease. This systematic review aims to critically evaluate the current molecular observations regarding the pathogenesis of PG and discuss associations with clinical characteristics as well as the evidence supporting novel cell types and immune pathways in PG.
Topics: Dermatitis; Hidradenitis Suppurativa; Humans; Inflammatory Bowel Diseases; Neutrophils; Pyoderma Gangrenosum
PubMed: 35114021
DOI: 10.1111/exd.14534 -
Acta Anaesthesiologica Scandinavica Sep 2014Clinicians and researchers frequently use the phrase 'feeding intolerance' (FI) as a descriptive term in enterally fed critically ill patients. We aimed to: (1)... (Meta-Analysis)
Meta-Analysis Review
Clinicians and researchers frequently use the phrase 'feeding intolerance' (FI) as a descriptive term in enterally fed critically ill patients. We aimed to: (1) determine what is the most accepted definition of FI; (2) estimate the prevalence of FI; and (3) evaluate whether FI is associated with important outcomes. Systematic searches of peer-reviewed publications using PubMed, MEDLINE, and Web of Science were performed with studies reporting FI extracted. We identified 72 studies defining FI. In 33 studies, the definition was based on large gastric residual volumes (GRVs) together with other gastrointestinal symptoms, while 30 studies relied solely on large GRVs, six studies used inadequate delivery of enteral nutrition (EN) as a threshold, and three studies gastrointestinal symptoms without reference to GRV. The median volume used to define a 'large' GRV was 250 ml (ranges from 75 to 500 ml). The pooled proportion (n = 31 studies) of FI was 38.3% (95% CI 30.7-46.2). Five studies reported outcomes, all of them observed adverse outcome in FI patients. In three studies, respectively, FI was associated with increased mortality and ICU length-of-stay. In summary, FI is inconsistently defined but appears to occur frequently. There are preliminary data indicating that FI is associated with adverse outcomes. A standard definition of FI is required to determine the accuracy of these preliminary data.
Topics: Abdominal Pain; Critical Care; Diarrhea; Energy Intake; Enteral Nutrition; Gastric Emptying; Gastrointestinal Contents; Humans; Ileus; Intubation, Gastrointestinal; Length of Stay; Nutritional Support; Observational Studies as Topic; Prevalence; Prospective Studies; Research Design; Retrospective Studies; Symptom Assessment; Treatment Outcome; Vomiting
PubMed: 24611520
DOI: 10.1111/aas.12302 -
Critical Care (London, England) Dec 2015Intracranial pressure (ICP) measurement is used to tailor interventions and to assist in formulating the prognosis for traumatic brain injury patients. Accurate data are... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Intracranial pressure (ICP) measurement is used to tailor interventions and to assist in formulating the prognosis for traumatic brain injury patients. Accurate data are therefore essential. The aim of this study was to verify the accuracy of ICP monitoring systems on the basis of a literature review.
METHODS
A PubMed search was conducted from 1982 to 2014, plus additional references from the selected papers. Accuracy was defined as the degree of correspondence between the pressure read by the catheter and a reference "real" ICP measurement. Studies comparing simultaneous readings from at least two catheters were included. Drift was defined as the loss of accuracy over the monitoring period. Meta-analyses of data from the studies were used to estimate the overall mean difference between simultaneous ICP measurements and their variability. Individual studies were weighted using both a fixed and a random effects model.
RESULTS
Of 163 articles screened, 83 compared two intracranial catheters: 64 reported accuracy and 37 drift (some reported both). Of these, 10 and 17, respectively, fulfilled the inclusion criteria for accuracy and zero drift analysis. The combined mean differences between probes were 1.5 mmHg (95 % confidence interval (CI) 0.7-2.3) with the random effects model and 1.6 mmHg (95 % CI 1.3-1.9) with the fixed effects model. The reported mean drift over a long observation period was 0.75 mmHg. No relation was found with the duration of monitoring or differences between various probes.
CONCLUSIONS
This study confirms that the average error between ICP measures is clinically negligible. The random effects model, however, indicates that a high percentage of readings may vary over a wide range, with clinical implications both for future comparison studies and for daily care.
Topics: Brain Injuries; Humans; Intracranial Pressure; Monitoring, Physiologic; Reproducibility of Results
PubMed: 26627204
DOI: 10.1186/s13054-015-1137-9 -
Pediatric Pulmonology Aug 2021To provide a systematic review of the existing pediatric decannulation protocols, including the role of polysomnography, and their clinical outcomes. (Review)
Review
OBJECTIVE
To provide a systematic review of the existing pediatric decannulation protocols, including the role of polysomnography, and their clinical outcomes.
METHODS
Five online databases were searched from database inception to May 29, 2020. Study inclusion was limited to publications that evaluated tracheostomy decannulation in children 18 years of age and younger. Data extracted included patient demographics and primary indication for tracheostomy. Methods used to assess readiness for decannulation were noted including the use of bronchoscopy, tracheostomy tube modifications, and gas exchange measurements. After decannulation, details regarding mode of ventilation, location, and length of observation period, and clinical outcomes were also collected. Descriptive statistical analyses were performed.
RESULTS
A total of 24 studies including 1395 children were reviewed. Tracheostomy indications included upper airway obstruction at a well-defined anatomic site (35%), upper airway obstruction not at a well-defined site (12%) and need for long-term ventilation and pulmonary care (53%). Bronchoscopy was routinely used in 23 of 24 (96%) protocols. Tracheostomy tube modifications in the protocols included capping (n = 20, 83%), downsizing (n = 14, 58%), and fenestrations (n = 2, 8%). Measurements of gas exchange included polysomnography (n = 13/18, 72%), oximetry (n = 10/18, 56%), blood gases (n = 3,17%), and capnography (n = 3, 17%). After decannulation, children in 92% of protocols were transitioned to room air. Observation period of 48 h or less was used in 76% of children.
CONCLUSIONS
There exists large variability in pediatric decannulation protocols. Polysomnography plays an integral role in assessing most children for tracheostomy removal. Evidence-based guidelines to standardize pediatric tracheostomy care remain an urgent priority.
Topics: Bronchoscopy; Child; Clinical Protocols; Device Removal; Humans; Polysomnography; Retrospective Studies; Tracheostomy
PubMed: 34231976
DOI: 10.1002/ppul.25503 -
Annals of Vascular Surgery Feb 2018Endovascular chimney technique has been increasingly reported in treating aortic arch pathologies. However, there are still concerns about this technique. The aim of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Endovascular chimney technique has been increasingly reported in treating aortic arch pathologies. However, there are still concerns about this technique. The aim of this study is to evaluate the safety and outcome of this technique by performing a systematic review and meta-analysis.
METHODS
Medline, EMBASE, and Cochrane databases were systematically searched to identify studies on the management of aortic arch pathologies using chimney technique. Studies were reviewed and selected using a priori defined criteria by 2 independent observers who abstracted data on study characteristics, study quality, and outcomes. The extracted data were presented as rate and were converted through arcsine transformations. Individual studies were evaluated and analyzed for 5 ending factors such as technical success, 30-day mortality, patency, perioperative endoleak, and stroke. Heterogeneity of the studies was determined using the chi-square distribution-based Q test and quantified by I statistics. The meta-analyses were performed using both random effects model and fixed-effect model.
RESULTS
Twelve studies with a total of 379 patients met the inclusion criteria. The pooled technical success rate of chimney technique was 91% (95% confidence interval [CI]: 87-94%). After patients were treated with chimney technique, the rate of 30-day mortality was 4% (95% CI: 2-7%), the rate of patency was 93% (95% CI: 89-96%), the rate of perioperative endoleak was 21% (95% CI: 17-26%), and the rate of stroke was 5% (95% CI: 3-8%).
CONCLUSIONS
This study indicates that using chimney technique for treating aortic arch pathologies produced satisfied midterm outcomes in both elective and emergent situations.
Topics: Adult; Aged; Aged, 80 and over; Aorta, Thoracic; Aortic Diseases; Blood Vessel Prosthesis; Blood Vessel Prosthesis Implantation; Chi-Square Distribution; Elective Surgical Procedures; Emergencies; Endovascular Procedures; Female; Humans; Male; Middle Aged; Postoperative Complications; Risk Factors; Stents; Treatment Outcome; Young Adult
PubMed: 28943484
DOI: 10.1016/j.avsg.2017.09.006 -
Clinical Pharmacokinetics Apr 2016Metformin has been available since 1957. Over 50 years later, one can legitimately question whether a clear definition of its "therapeutic concentrations" is available. (Review)
Review
BACKGROUND
Metformin has been available since 1957. Over 50 years later, one can legitimately question whether a clear definition of its "therapeutic concentrations" is available.
OBJECTIVE
The objective of this systematic review was to establish whether or not there is a literature consensus on the "therapeutic concentrations" of metformin.
METHODS
We systematically searched the scientific literature with the keywords "metformin", "therapeutic concentration", "therapeutic level", and "therapeutic range". When the suggested values were defined by citing a literature reference, the types of studies in cited references and the concordance of data between the citations and theirs sources were studied.
RESULTS
We identified 120 documents that reported or cited 65 different "therapeutic" plasma metformin concentrations or ranges. The values ranged from 0.129 to 90 mg/L, and the lowest and highest boundaries were 0 and 1800 mg/L. Only four original research studies determined a "therapeutic concentration". Fifty-four publications cited previous studies as defining the therapeutic concentrations, whereas 62 publications mentioned "therapeutic concentrations" but did not even cite a supporting reference. The supporting references were mostly reviews, pharmacokinetic studies and in vitro studies. In the 54 publications that cited references, concordance between the wording of the citation and the true nature of the source data was observed in only 23 cases (42.6%).
LIMITATIONS
Given the nature of a systematic literature search, the only possible limitation would be incomplete identification and retrieval of publications on therapeutic concentrations. An extensive study of the literature has, however, been performed by examining nearly 1000 potentially relevant publications.
GUIDANCE FOR CLINICAL PRACTICE
The only valid way of defining the therapeutic concentration window for metformin would be to relate dose efficacy (in terms of blood glucose control) to the corresponding plasma concentration in long-term treated patients.
CONCLUSIONS
Although metformin has been available for over 50 years and it is the key medication in first-line treatment of type 2 diabetes mellitus, major methodological and/or conceptual errors have confounded the literature on its therapeutic concentrations.
Topics: Animals; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Dosage Calculations; Humans; Hypoglycemic Agents; Metformin
PubMed: 26330026
DOI: 10.1007/s40262-015-0323-x -
Technology and Health Care : Official... 2012Research and development in the art of cycling using functional electrical stimulation (FES) of the paralysed leg muscles has been going on for around thirty years. A... (Review)
Review
Research and development in the art of cycling using functional electrical stimulation (FES) of the paralysed leg muscles has been going on for around thirty years. A range of physiological benefits has been observed in clinical studies but an outstanding problem with FES-cycling is that efficiency and power output are very low. The present work had the following aims: (i) to provide a tutorial introduction to a novel framework and methods of estimation of metabolic efficiency using example data sets, and to propose benchmark measures for evaluating FES-cycling performance; (ii) to systematically review the literature pertaining specifically to the metabolic efficiency of FES-cycling, to analyse the observations and possible explanations for the low efficiency, and to pose hypotheses for future studies which aim to improve performance. We recommend the following as benchmark measures for assessment of the performance of FES-cycling: (i) total work efficiency, delta efficiency and stimulation cost; (ii) we recommend, further, that these benchmark measures be complemented by mechanical measures of maximum power output, sustainable steady-state power output and endurance. Performance assessments should be carried out at a well-defined operating point, i.e. under conditions of well controlled work rate and cadence, because these variables have a strong effect on energy expenditure. Future work should focus on the two main factors which affect FES-cycling performance, namely: (i) unfavourable biomechanics, i.e. crude recruitment of muscle groups, non-optimal timing of muscle activation, and lack of synergistic and antagonistic joint control; (ii) non-physiological recruitment of muscle fibres, i.e. mixed recruitment of fibres of different type and deterministic constant-frequency stimulation. We hypothesise that the following areas may bring better FES-cycling performance: (i) study of alternative stimulation strategies for muscle activation including irregular stimulation patterns (e.g. doublets, triplets, stochastic patterns) and variable frequency stimulation trains, where it appears that increasing frequency over time may be profitable; (ii) study of better timing parameters for the stimulated muscle groups, and addition of more muscle groups: this path may be approached using EMG studies and constrained numerical optimisation employing dynamic models; (iii) development of optimal stimulation protocols for muscle reconditioning and FES-cycle training.
Topics: Bicycling; Biomechanical Phenomena; Electric Stimulation Therapy; Energy Metabolism; Energy Transfer; Humans; Leg; Muscle, Skeletal; Nervous System Diseases; Paraplegia; Spinal Cord Injuries
PubMed: 23079945
DOI: 10.3233/THC-2012-0689