Evaluating the variation in the strength of the effect across studies is a key feature of meta-analyses. This variability is reflected by measures like τ(2) or I(2), but their clinical interpretation ...is not straightforward. A prediction interval is less complicated: it presents the expected range of true effects in similar studies. We aimed to show the advantages of having the prediction interval routinely reported in meta-analyses.
We show how the prediction interval can help understand the uncertainty about whether an intervention works or not. To evaluate the implications of using this interval to interpret the results, we selected the first meta-analysis per intervention review of the Cochrane Database of Systematic Reviews Issues 2009-2013 with a dichotomous (n=2009) or continuous (n=1254) outcome, and generated 95% prediction intervals for them.
In 72.4% of 479 statistically significant (random-effects p<0.05) meta-analyses in the Cochrane Database 2009-2013 with heterogeneity (I(2)>0), the 95% prediction interval suggested that the intervention effect could be null or even be in the opposite direction. In 20.3% of those 479 meta-analyses, the prediction interval showed that the effect could be completely opposite to the point estimate of the meta-analysis. We demonstrate also how the prediction interval can be used to calculate the probability that a new trial will show a negative effect and to improve the calculations of the power of a new trial.
The prediction interval reflects the variation in treatment effects over different settings, including what effect is to be expected in future patients, such as the patients that a clinician is interested to treat. Prediction intervals should be routinely reported to allow more informative inferences in meta-analyses.
Abstract Context Correct assessment of tumour stage is crucial for prostate cancer (PCa) management. Objective To assess the diagnostic accuracy of magnetic resonance imaging (MRI) for local PCa ...staging and explore the influence of different imaging protocols. Evidence acquisition We searched the PubMed, Embase, and Cochrane databases from 2000 up to August 2014. We included studies that used MRI for detection of extracapsular extension (ECE; T3a), seminal vesicle invasion (SVI; T3b), or overall stage T3 PCa, with prostatectomy as the reference standard. Methodologic quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies tool by two independent reviewers. Data necessary to complete 2 × 2 tables were obtained, and patient, study, and imaging characteristics were extracted. Accuracy was reported for the most experienced or first reader. Results were pooled and plotted in summary receiver operating characteristics plots. Evidence synthesis A total of 75 studies (9796 patients) could be analysed. Pooled data for ECE (45 studies, 5681 patients), SVI (34 studies, 5677 patients), and overall stage T3 detection (38 studies, 4001 patients) showed sensitivity and specificity of 0.57 (95% confidence interval CI 0.49–0.64) and 0.91 (95% CI 0.88–0.93), 0.58 (95% CI 0.47–0.68) and 0.96 (95% CI 0.95–0.97), and 0.61 (95% CI 0.54–0.67) and 0.88 (95% CI 0.85–0.91), respectively. Functional imaging in addition to T2-weighted imaging and use of higher field strengths (3 T) improved sensitivity for ECE and SVI. ECE sensitivity was not improved by endorectal coil use. Conclusions MRI has high specificity but poor and heterogeneous sensitivity for local PCa staging. An endorectal coil showed no additional benefit for ECE detection, but slightly improved sensitivity for SVI detection. Higher field strengths and the use of functional imaging techniques can slightly improve sensitivity. Patient summary We pooled the results from all previous studies that evaluated magnetic resonance imaging (MRI) for detection of tumour growth outside the prostate. MRI is not sensitive enough to find all tumours with extraprostatic growth.
The discussion on the use of bevacizumab is still ongoing and often doctors are deterred from using bevacizumab due to legal or political issues. Bevacizumab is an effective, safe and inexpensive ...treatment option for neovascular age-related macular degeneration (AMD), albeit unregistered for the disease. Therefore, in some countries ophthalmologists use the equally effective but expensive drugs ranibizumab and aflibercept. We describe the economic consequences of this dilemma surrounding AMD treatment from a societal perspective.
We modelled cost-effectiveness of treatment with ranibizumab (as-needed), aflibercept (bimonthly) and bevacizumab (as-needed). Effectiveness was estimated by systematic review and meta-analysis. The drug with the most favourable cost-effectiveness profile compared to bevacizumab was used for threshold analyses. First, we determined how much we overspend per injection. Second, we calculated the required effectiveness to justify the current price and the reasonable price for a drug leading to optimal vision. Finally, we estimated how much Europe overspends if bevacizumab is not first choice.
Bevacizumab treatment costs €27,087 per year, about €4,000 less than aflibercept and €6,000 less than ranibizumab. With similar effectiveness for all drugs as shown by meta-analysis, bevacizumab was the most cost-effective. Aflibercept was chosen for threshold analyses. Aflibercept costs €943 per injection, but we determined that the maximum price to be cost-effective is €533. Alternatively, at its current price, aflibercept should yield about twice the visual gain. Even when optimal vision can be achieved, the maximum price for any treatment is €37,453 per year. Most importantly, Europe overspends €335 million yearly on AMD treatment when choosing aflibercept over bevacizumab.
Bevacizumab is the most cost-effective treatment for AMD, yet is not the standard of care across Europe. The registered drugs ranibizumab and aflibercept lead to large overspending without additional health benefits. Health authorities should consider taking steps to implement bevacizumab into clinical practice as first choice.
Respiratory syncytial virus (RSV) infection is associated with subsequent recurrent wheeze. Observational studies cannot determine whether RSV infection is the cause of recurrent wheeze or the first ...indication of preexistent pulmonary vulnerability in preterm infants. The monoclonal antibody palivizumab has shown efficacy in preventing severe RSV infection in high-risk infants.
In the double-blind, placebo-controlled MAKI trial, we randomly assigned 429 otherwise healthy preterm infants born at a gestational age of 33 to 35 weeks to receive either monthly palivizumab injections (214 infants) or placebo (215 infants) during the RSV season. The prespecified primary outcome was the total number of parent-reported wheezing days in the first year of life. Nasopharyngeal swabs were taken during respiratory episodes for viral analysis.
Palivizumab treatment resulted in a relative reduction of 61% (95% confidence interval, 56 to 65) in the total number of wheezing days during the first year of life (930 of 53,075 days in the RSV-prevention group 1.8% vs. 2309 of 51,726 days 4.5% in the placebo group). During this time, the proportion of infants with recurrent wheeze was 10 percentage points lower in patients treated with palivizumab (11% vs. 21%, P=0.01).
In otherwise healthy preterm infants, palivizumab treatment resulted in a significant reduction in wheezing days during the first year of life, even after the end of treatment. These findings implicate RSV infection as an important mechanism of recurrent wheeze during the first year of life in such infants. (Funded by Abbott Laboratories and by the Netherlands Organization for Health Research and Development; MAKI Controlled Clinical Trials number, ISRCTN73641710.).
The purpose of this diagnostic meta-analysis was to determine the diagnostic accuracy of multiparametric MRI for prostate cancer detection using anatomic T2-weighted imaging combined with two ...functional techniques: diffusion-weighted imaging (DWI) and dynamic contrast-enhanced MRI (DCE-MRI).
We searched electronic databases, including MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) up to February 3, 2012. We included diagnostic accuracy studies using a combination of T2-weighted imaging, DWI, and DCE-MRI to detect prostate cancer with histopathologic data from prostatectomy or biopsy as the reference standard. The methodologic quality was assessed with version 2 of the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool by two independent reviewers. Sensitivity and specificity of all studies were calculated from 2 × 2 tables, and the results were plotted in a hierarchic summary receiver operating characteristic plot.
Seven studies that met the inclusion criteria (526 patients) could be analyzed. The pooled data showed a specificity of 0.88 (95% CI, 0.82-0.92) and sensitivity of 0.74 (95% CI, 0.66-0.81) for prostate cancer detection, with negative predictive values (NPVs) ranging from 0.65 to 0.94. Subgroup analyses showed no significant difference between the subgroups.
The high specificity with variable but high NPVs and sensitivities implies a potential role for multiparametric MRI in detecting prostate cancer.
SYRCLE's risk of bias tool for animal studies Hooijmans, Carlijn R; Rovers, Maroeska M; de Vries, Rob B M ...
BMC medical research methodology,
03/2014, Volume:
14, Issue:
1
Journal Article
Peer reviewed
Open access
Systematic Reviews (SRs) of experimental animal studies are not yet common practice, but awareness of the merits of conducting such SRs is steadily increasing. As animal intervention studies differ ...from randomized clinical trials (RCT) in many aspects, the methodology for SRs of clinical trials needs to be adapted and optimized for animal intervention studies. The Cochrane Collaboration developed a Risk of Bias (RoB) tool to establish consistency and avoid discrepancies in assessing the methodological quality of RCTs. A similar initiative is warranted in the field of animal experimentation.
We provide an RoB tool for animal intervention studies (SYRCLE's RoB tool). This tool is based on the Cochrane RoB tool and has been adjusted for aspects of bias that play a specific role in animal intervention studies. To enhance transparency and applicability, we formulated signalling questions to facilitate judgment.
The resulting RoB tool for animal studies contains 10 entries. These entries are related to selection bias, performance bias, detection bias, attrition bias, reporting bias and other biases. Half these items are in agreement with the items in the Cochrane RoB tool. Most of the variations between the two tools are due to differences in design between RCTs and animal studies. Shortcomings in, or unfamiliarity with, specific aspects of experimental design of animal studies compared to clinical studies also play a role.
SYRCLE's RoB tool is an adapted version of the Cochrane RoB tool. Widespread adoption and implementation of this tool will facilitate and improve critical appraisal of evidence from animal studies. This may subsequently enhance the efficiency of translating animal research into clinical practice and increase awareness of the necessity of improving the methodological quality of animal studies.
Inadequate margins continue to occur frequently in patients who undergo surgical resection of a tumor, suggesting that current intraoperative methods are not sufficiently reliable in determining the ...margin status. This clinical demand has inspired the development of many novel imaging techniques that could help surgeons with intraoperative margin assessment. This systematic review provides an overview of novel imaging techniques for intraoperative margin assessment in surgical oncology, and reports on their technical properties, feasibility in clinical practice and diagnostic accuracy. PubMed, Embase, Web of Science and the Cochrane library were systematically searched (2013‐2018) for studies reporting on imaging techniques for intraoperative margin assessment. Patient and study characteristics, technical properties, feasibility characteristics and diagnostic accuracy were extracted. This systematic review identified 134 studies that investigated and developed 16 groups of techniques for intraoperative margin assessment: fluorescence, advanced microscopy, ultrasound, specimen radiography, optical coherence tomography, magnetic resonance imaging, elastic scattering spectroscopy, bio‐impedance, X‐ray computed tomography, mass spectrometry, Raman spectroscopy, nuclear medicine imaging, terahertz imaging, photoacoustic imaging, hyperspectral imaging and pH measurement. Most studies were in early developmental stages (IDEAL 1 or 2a, n = 98); high‐quality stage 2b and 3 studies were rare. None of the techniques was found to be clearly superior in demonstrating high feasibility as well as high diagnostic accuracy. In conclusion, the field of imaging techniques for intraoperative margin assessment is highly evolving. This review provides a unique overview of the opportunities and limitations of the currently available imaging techniques.
What's new?
While surgical resection is critical in the treatment of primary solid tumors, resection at tumor margins remains problematic, with inadequately resected margins facilitating tumor recurrence. In this systematic review, the authors collected information on novel imaging techniques applied to the intraoperative assessment of tumor margins across cancer types. A total of 16 groups of techniques were identified, with many in early stages of clinical application. Following comparison, no single technique was clearly superior in clinical feasibility or diagnostic accuracy. The review highlights the evolving nature of imaging techniques for intraoperative margin assessment and identifies opportunities and limitations in the field.
The shift from open to minimally invasive procedures with growing complexity has increased the demand for advanced intraoperative medical technologies. The hybrid operating room (OR) combines the ...functionality of a standard OR with fixed advanced imaging systems to facilitate minimally invasive image-guided procedures.
This systematic scoping review provides an overview of the use of the hybrid OR over the years, and reports on the encountered advantages and challenges.
We conducted a systematic search in PubMed, Embase, Web of Science, and Cochrane library databases for studies that described procedures being performed with the aid of 3D imaging in the hybrid OR.
The search identified 123 studies that described 44 distinct procedures, divided over nine clinical disciplines. The number of studies increased from two in 2010 to 15 in the first five months of 2020. Ninety-nine (80%) of the studies described how 3D imaging was performed in the hybrid OR; 95 (96%) used cone-beam CT; four (4%) used multi-detector CT. Advantages and challenges of the hybrid OR were described in 94 (76%) and 34 (35%) studies, respectively. The most frequently reported advantage of using a hybrid OR is the achievement of more accurate treatment results, whereas elongation of the procedure time is the most important challenge, followed by an increase in radiation dose.
In conclusion, the growing number of clinical disciplines that uses the hybrid OR shows its wide functionality. To optimize its use, future comparative studies should be conducted to investigate which procedures really benefit from being performed in the hybrid OR.
Abstract Otitis media (OM) is one of the most frequent diseases in young children, one of the most common reasons for a child to visit a physician, and also the most common indication for antibiotic ...prescribing. OM-related hearing loss due to middle ear effusion can delay language acquisition, alter behaviour, and influence quality of life. Conclusive evidence is, however, lacking. More insight into the individual risk factors is required in order to answer the question of why some children recover from OM spontaneously while others need specific intervention.
Summary Background Estimating attributable mortality of ventilator-associated pneumonia has been hampered by confounding factors, small sample sizes, and the difficulty of doing relevant subgroup ...analyses. We estimated the attributable mortality using the individual original patient data of published randomised trials of ventilator-associated pneumonia prevention. Methods We identified relevant studies through systematic review. We analysed individual patient data in a one-stage meta-analytical approach (in which we defined attributable mortality as the ratio between the relative risk reductions RRR of mortality and ventilator-associated pneumonia) and in competing risk analyses. Predefined subgroups included surgical, trauma, and medical patients, and patients with different categories of severity of illness scores. Findings Individual patient data were available for 6284 patients from 24 trials. The overall attributable mortality was 13%, with higher mortality rates in surgical patients and patients with mid-range severity scores at admission (ie, acute physiology and chronic health evaluation score APACHE 20–29 and simplified acute physiology score SAPS 2 35–58). Attributable mortality was close to zero in trauma, medical patients, and patients with low or high severity of illness scores. Competing risk analyses could be done for 5162 patients from 19 studies, and the overall daily hazard for intensive care unit (ICU) mortality after ventilator-associated pneumonia was 1·13 (95% CI 0·98–1·31). The overall daily risk of discharge after ventilator-associated pneumonia was 0·74 (0·68–0·80), leading to an overall cumulative risk for dying in the ICU of 2·20 (1·91–2·54). Highest cumulative risks for dying from ventilator-associated pneumonia were noted for surgical patients (2·97, 95% CI 2·24–3·94) and patients with mid-range severity scores at admission (ie, cumulative risks of 2·49 1·81–3·44 for patients with APACHE scores of 20–29 and 2·72 1·95–3·78 for those with SAPS 2 scores of 35–58). Interpretation The overall attributable mortality of ventilator-associated pneumonia is 13%, with higher rates for surgical patients and patients with a mid-range severity score at admission. Attributable mortality is mainly caused by prolonged exposure to the risk of dying due to increased length of ICU stay. Funding None.
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