Diagnosis of epidural expansion
Uitgangsvraag
Research question
What is the added value of MRI in patients with spinal metastases already visible on recent CT for detecting (the extent of) epidural tumor extension?
Aanbeveling
Recommendations
- For a patient known to have vertebral metastases who presents with new neurological deficits (or back pain), first check whether a recent CT scan (<1 month old) of the entire spine already shows epidural extension of a metastasis.
- Consider omitting an additional MRI if:
- the symptoms can be adequately explained by a recent CT; and
- an MRI is not necessary to determine the treatment modality.
- Perform an additional MRI to:
- assess the extent of involvement and any compression of the spinal cord; or
- identify other levels with more subtle extensions.
Overwegingen
Considerations
Balance Between Desired and Undesired Effects
In the above-mentioned study by Hallinan et al. (2022) from Singapore, 101 patients with vertebral metastases and epidural extension visible on MRI were evaluated, all of whom had recently undergone a CT scan. The study demonstrated that, in the original CT scan reports, the sensitivity for detecting epidural extension was low (44–49%). When the scans were specifically reviewed for the study, sensitivity markedly increased (74–98%). The study reported a high specificity, particularly for detecting high-grade epidural extension (so-called Bilsky grade 3), ranging from 97% to 100%. Low-grade epidural extension showed a lower specificity (64–100%), with false positives mainly caused by venous structures or degenerative changes.
Possible explanations for the initially low sensitivity include the subtle appearance of epidural extension on axial images with thick slices, the lack of routine evaluation of the spinal canal in a soft-tissue window setting, insufficient image magnification, and comparison only with prior CT scans rather than MRI.
Other studies have shown similar findings:
- In 2011, Crocker et al. investigated 44 patients in the United Kingdom and also observed epidural extension on CT in 89% of patients who had this on an MRI (sensitivity 89%, specificity 92%) (Crocker, 2011).
- Catherine et al. (2015) published a smaller study of 27 emergency CT scans performed during weekends in patients with spinal metastases and neurological symptoms. Of the 13 patients with confirmed epidural extension in MRI, 12 already demonstrated this finding on recent CT (Catherine, 2015).
- Finally, Kim et al. (2023) evaluated 293 patients with MESCC on MRI. In their dedicated CT review, epidural extension was visible in 81% of cases, while the original CT reports had a markedly lower sensitivity of 65%.
In summary, it is evident that epidural extension is frequently missed in the initial CT interpretation, whereas a dedicated review achieves high sensitivity and specificity for detecting severe epidural extension/stenosis (Bilsky 3). None of the above studies, however, propose omitting MRI altogether; MRI remains the gold standard for determining the exact extent of disease, differentiating from other pathologies such as disc disease, and assessing spinal cord involvement or myelopathy. The authors do, however, advocate triage based on CT findings to help determine the urgency of MRI and/or referral to a neuro-oncological center for potential radiotherapy or surgery.
There may be a slight preference for contrast-enhanced CT compared with non-contrast CT when assessing epidural extension (Kim et al. 2023), although this difference was not statistically significant. Low-dose CT scans were not evaluated.
Other Guidelines
The NICE guideline (2023) mentions CT only for the assessment of epidural extension in the context of contraindications to MRI and clarifies that both MRI and CT are desirable for the precise evaluation of respectively soft tissue and bone involvement.
Translation to Dutch Clinical Practice
It appears realistic that epidural extension is often missed during the initial CT evaluation but can often be identified upon dedicated re-assessment. Such findings are often subtle. Although MRI remains the gold standard, in patients with known spinal metastases and new symptoms, reviewing a recent CT scan for possible (high-grade) epidural extension may be worthwhile.
This approach could spare many patients an MRI scan, saving them time and energy, and potentially avoiding an anxiety-provoking experience, as claustrophobia is relatively common during MRI procedures. Moreover, identifying epidural extension earlier on routine oncologic staging CT may enable faster treatment initiation, as management can be planned sooner than if triggered only after MRI confirmation.
Quality of Evidence
For the distinction between high-grade and non–high-grade (low/normal) MESCC, the quality of evidence for sensitivity is rated as low. This rating is based on concerns about applicability (risk of bias) due to the large discrepancies between initial reports and study re-assessments, as well as unexplained interobserver variability between two equally experienced radiologists (inconsistency).
For the distinction between normal and non-normal MESCC, the quality of evidence for sensitivity is moderate. Here too, applicability concerns exist because of the same discrepancies between routine reporting and dedicated study review, and the unexplained differences in specificity between the two radiologists (inconsistency).
Patient Values and Preferences
It is expected that patients will appreciate not having to undergo an additional MRI scan if epidural extension is already clearly visible on CT and a treatment plan can be made based on those findings.
Cost Considerations
This intervention may reduce costs compared with standard care, as no additional MRI scan would be required when epidural extension is clearly seen on CT. Early detection of epidural extension could also decrease the number of emergency MRI indications and urgent interventions, allowing imaging and treatment to occur during regular working hours, thus saving both staff time and financial resources.
Equity
The intervention does not appear to affect health equity, as all patients would still remain eligible for (MRI) imaging when clinically indicated.
Acceptability and Ethical Considerations
As noted above, no imaging is withheld from patients. The goal is earlier detection of spinal metastases and the avoidance of unnecessary imaging.
Sustainability
Sustainability considerations play a minor role in these recommendations. In some cases, an additional MRI scan can be avoided, thereby reducing resource use.
Feasibility
Following the current recommendations may reduce logistical demands on nursing and radiology staff. Hospital stay duration may decrease, and MRI-related costs can be reduced. Less rescheduling would be required in already full MRI schedules. Earlier detection of epidural extension on CT may also reduce emergency consultations and discussions, allowing for more routine care delivery.
Onderbouwing
Background
Currently, virtually all patients with known vertebral metastases undergo an MRI scan when they exhibit neurologic symptoms of metastatic epidural spinal cord compression (MESCC). However, in case of clear epidural extension, this can often already be seen on a recent CT scan (albeit in retrospect) (Hallinan, 2021; Kim, 2023). If this CT scan suffices for subsequent radiotherapy and/or surgical planning, this could potentially eliminate the need for an MRI scan. This would reduce patient handling time and decrease the demand for MRI resources. thereby saving time and energy for both patients and increasingly scarce hospital personnel, while also lowering costs and environmental burden of the MRI. Subsequently, the necessary spinal surgery or radiotherapy can be planned and initiated without having to wait for an MRI scan.
The current question is thus: What is the added value of MRI in patients with vertebral metastases with already clear epidural extension on a recent CT scan?
Conclusions
|
Low GRADE |
The use of CT alone may yield comparable sensitivity to a diagnostic approach that includes both CT and a follow-up MRI for assessing MESCC (normal versus. low/high compression) in patients with symptomatic spinal metastases visible on an existing CT scan.
Source: (Hallinan, 2022) |
|
Moderate GRADE |
The use of CT alone yield comparable sensitivity to a diagnostic approach that includes both CT and a follow-up MRI for assessing MESCC (normal/low versus high compression) in patients with symptomatic spinal metastases visible on an existing CT scan.
Source: (Hallinan, 2022) |
Summary of literature
Description of studies
One study was included in the analysis of the literature. Important study characteristics and results are summarized in Table 1. The assessment of the risk of bias is summarized in the risk of bias table.
Table 1. Characteristics of included studies
|
Study reference |
Study characteristics |
Patient characteristics
|
Index test (test of interest) |
Reference test
|
Follow-up |
Outcome measures and effect size |
Risk of bias/ Comments |
||||||||||||||||||||||||||||
|
Hallinan, 2022 |
Type of study: Cross-sectional study? Setting and country: the National University Hospital, Singapore
Funding and conflicts of interest: None to declare. |
Patients with known spinal column metastatic disease and suspicion of MESCC was undertaken from 2007 till 2021 in a single hospital. Inclusion criteria: Aged ≥18 years; with imaging examinations obtained across different MRI scanners and CT platforms; Staging CT scans and corresponding MRI spine studies with a time gap of up to 1 month (30 days); CT scans with intravenous contrast were Used.
Exclusion criteria: 1) CT scans performed without contrast (24/549, 4.4%). 2) staging CT scans with No corresponding MRI study or CT scans performed post-MRI (313/549, 57.0%); 3) greater than a 30-day gap between the CT and MRI (131/549, 23.9%); 4) CT images unavailable for extraction (81/549, 14.8%).
N=101/369 (27.3%) CT studies N=123 /672 (18.3%)
Prevalence: Not reported.
Mean age ± SD: 60 ±11.6 Sex: 53.5% M / 46.5% F
Other important characteristics: MESCC location per CT scan
# Two or more sites of MESCC. |
Describe index test: CT: Philips, General Electric, and Siemens platforms. CT scans with intravenous contrast.
Prior to labeling, all body radiologists were provided with a visual MESCC grading scale and reviewed practice studies providing each axial CT image in consensus with the corresponding MRI (performed within one examples of low and high-grade MESCC on MRI, and CT scans side by side.
Comparator test: Not applicable.
|
Describe reference test: MRI scanners within 30 days. (General Electric and Siemens) using axial T2-weighted images for comparison with the staging CT.
Two expert radiologists provided the reference standard using MRI scans performed within 30 days. Reference standard MESCC gradings on CT were provided in consensus via two spine radiologists (11 and 7 years of experience) analyzing the MRI scans.
|
Time between the index test and reference test: Less than 30 days.
For how many participants were no complete outcome data available? N (%) unknown because only patients with both CT and MRI scans were included.
Reasons for incomplete outcome data described? Unknown, because only patients with both CT and MRI scans on which the outcome could be evaluated were included. |
MESCC (normal/low versus high) Sensitivity, specifity, area under the curve.
MESCC (normal versus low/high)
Sensitivity, specifity, area under the curve.
|
Risk of bias:
Details please see the risk of bias table. |
||||||||||||||||||||||||||||
Results
Table 2. Diagnostic accuracy per CT scan
|
MESCC (normal/low versus high per CT scan) N=101, CT studies=123 |
|||
|
|
Sens |
Spec |
AUROC |
|
R1 (14 years) |
74.44 (64.16–83.06) |
100.00 (89.42–100.00) |
0.872 (0.827–0.918) |
|
R2 (13 years) |
94.44 (87.51–98.17) |
93.94 (79.77–99.26) |
0.942 (0.894–0.990) |
|
R3 (3 years) |
77.78 (67.79–85.87) |
96.97 (84.24–99.92) |
0.874 (0.821–0.926) |
|
Original report |
48.89 (38.20–59.65) |
90.91 (75.67–98.08) |
0.699 (0.627–0.771) |
|
|
|||
|
MESCC (normal versus low/high per CT scan) N=101, CT studies=123 |
|||
|
R1 (14 years) |
98.11 (93.35–99.77) |
82.35 (56.57–96.20) |
0.902 (0.808–0.997) |
|
R2 (13 years) |
98.11 (93.35–99.77) |
64.71 (38.33–85.79) |
0.814 (0.696–0.932) |
|
R3 (3 years) |
91.51 (84.49–96.04) |
82.35 (56.57–96.20) |
0.869 (0.772–0.966) |
|
Original report |
44.34 (34.69–54.31) |
100.00 (80.49–100.00) |
0.722 (0.674–0.769) |
|
R, Radiologist |
|||
Level of evidence of the literature
MESCC (normal/low versus high)
Sensitivity
The level of evidence regarding sensitivity was downgraded by 2 levels because of the study limitations (1 level for risk of bias: some concerns with respect to applicability) and the difference between radiologists with similar years of experience (1 level for inconsistence); Publication bias was not assessed.
Specificity
The level of evidence regarding specificity was downgraded by 1 level because of the study limitations (1 level for risk of bias: some concerns with respect to applicability); Publication bias was not assessed.
Area under the curve
The level of evidence regarding area under the curve was downgraded by 1 level because of the study limitations (1 level for risk of bias: some concerns with respect to applicability); Publication bias was not assessed.
MESCC (normal versus low/high)
Sensitivity
The level of evidence regarding sensitivity was downgraded by 1 level because of the study limitations (1 level for risk of bias: some concerns with respect to applicability); Publication bias was not assessed.
Specificity
The level of evidence regarding specificity was downgraded by 2 levels because of the study limitations (1 level for risk of bias: some concerns with respect to applicability) and the difference between radiologists with similar years of experience (1 level for inconsistence); Publication bias was not assessed.
Area under the curve
The level of evidence regarding area under the curve was downgraded by 1 level because of the study limitations (1 level for risk of bias: some concerns with respect to applicability); Publication bias was not assessed.
Search and select
A systematic review of the literature was performed to answer the following question(s):
What is the diagnostic accuracy with and without MRI in patients with symptomatic spinal metastases visible on existing CT scans?
PICO
| Patients | Patients with symptomatic spinal metastases visible on existing CT scans/an indication for surgery |
| Intervention | CT |
| Control |
CT+MRI |
| Reference | Determination of epidural extension during surgery, clinical follow-up, or later imaging with MRI or CT |
| Outcomes | Diagnostic accuracy for detecting epidural extension and/or the extent of extension (agreement on Bilsky grades) in adjacent vertebrae |
| T/S (Timing/Setting) |
Hospital |
Relevant outcome measures
The guideline panel considered sensitivity, and negative predictive value (NPV) as a critical outcome measure for decision making; and specificity and positive predictive value (PPV), Area Under the Curve (AUC), and accuracy as an important outcome measure for decision making.
A priori, the guideline panel did not define the outcome measures listed above but used the definitions used in the studies.
Search and select (Methods)
The databases Medline (via OVID) and Embase (via Embase.com) were searched with relevant search terms until April 9th, 2025. The detailed search strategy is listed under the tab ‘Literature search strategy’. The systematic literature search resulted in 376 hits. Studies were selected based on the following criteria:
- Patients with symptomatic spinal metastases identified on CT or an indication for surgery, and subsequently underwent MRI.
- Describing at least one of the relevant outcomes specified in the PICO.
Ten studies were initially selected based on title and abstract screening. After reading the full text, nine studies were excluded (see the table with reasons for exclusion under the tab Methods), and one study was included.
- 1 - Catherine G, MacLeod N, Sheridan S. Is CT adequate to assess for malignant cord compression?. Clinical Radiology. 2015 Sep 1;70:S7.
- 2 - Crocker M, Anthantharanjit R, Jones TL, Shoeb M, Joshi Y, Papadopoulos MC, Bell BA, Rich P. An extended role for CT in the emergency diagnosis of malignant spinal cord compression. Clinical radiology. 2011 Oct 1;66(10):922-7.
- 3 - Hallinan JT, Ge S, Zhu L, Zhang W, Lim YT, Thian YL, Jagmohan P, Kuah T, Lim DS, Low XZ, Teo EC. Diagnostic accuracy of CT for metastatic epidural spinal cord compression. Cancers. 2022 Aug 31;14(17):4231.
- 4 - Kim L, Narayanan D, Liu J, Pattanayak P, Turkbey E, Shen TC, Linehan WM, Pinto PA, Summers RM. Radiologic reporting of MRI-proven thoracolumbar epidural metastases on body CT: 12-Year single-institution experience. Clinical imaging. 2023 Oct 1;102:19-25.
- 5 - Qu X, Huang X, Yan W, Wu L, Dai K. A meta-analysis of 18FDG-PET–CT, 18FDG-PET, MRI and bone scintigraphy for diagnosis of bone metastases in patients with lung cancer. European journal of radiology. 2012 May 1;81(5):1007-15.
Evidence tables
Risk of bias assessment diagnostic accuracy studies (QUADAS II, 2011)
Research question: What is the diagnostic accuracy with and without MRI in patients with symptomatic spinal metastases visible on existing CT scans?
|
Study |
Patient selection |
Index test |
Reference standard |
Flow and timing |
Comments with respect to applicability |
||||||||||||||||||
|
Hallinan, 2022 |
Was a consecutive or random sample of patients enrolled? Probably yes (patients with MRI and CT studies were enrolled, data retrospectively retrieved)
Was a case-control design avoided? Yes
Did the study avoid inappropriate exclusions? Yes |
Were the index test results interpreted without knowledge of the results of the reference standard? Yes
If a threshold was used, was it pre-specified? A visual MESCC grading scale was pre-specified and pre-described. |
Is the reference standard likely to correctly classify the target condition? Yes
Were the reference standard results interpreted without knowledge of the results of the index test? No (The two radiologists labeled each axial CT image in consensus with the corresponding MRI (performed within one month) using an established visual Bilsky SOSG scale) |
Was there an appropriate interval between index test(s) and reference standard? Yes (<1 month)
Did all patients receive a reference standard? Yes (one of the inclusion criteria)
Did patients receive the same reference standard? Yes
Were all patients included in the analysis? Probably yes |
Are there concerns that the included patients do not match the review question? No
Are there concerns that the index test, its conduct, or interpretation differ from the review question? Yes (There are some concerns about why the CT scan labeling specific to this study differs significantly from the original report based on the same CT scans. The authors described this process as 'a dedicated radiologist review,' in which all body radiologists were provided with a visual MESCC grading scale and reviewed practice cases showing examples of low- and high-grade MESCC on MRI and CT scans side by side prior to labeling.)
Are there concerns that the target condition as defined by the reference standard does not match the review question? No |
||||||||||||||||||
|
CONCLUSION: Could the selection of patients have introduced bias?
RISK: LOW |
CONCLUSION: Could the conduct or interpretation of the index test have introduced bias?
RISK: LOW |
CONCLUSION: Could the reference standard, its conduct, or its interpretation have introduced bias?
RISK: LOW (In the context of the research question, the reference standard is typically applied with the knowledge of the index test) |
CONCLUSION Could the patient flow have introduced bias?
RISK: LOW |
|
|||||||||||||||||||
Table of excluded studies
|
|
Reference |
Reason for exclusion |
|
1. |
3-D CT is the most reliable imaging modality when quantifying glenoid bone loss shoulder |
Wrong outcome |
|
2. |
Zero echo time imaging of the shoulder: Enhanced osseous detail by using MR imaging |
Wrong outcome |
|
3. |
Does Bone Loss Imaging Modality, Measurement Methodology, and Interobserver Reliability Alter Treatment in Glenohumeral Instability? |
Wrong outcome |
|
4. |
3D-MRI FRACTURE Sequence is equivalent to 3D-CT in quantifying bone loss and measuring shoulder morphology in patients with shoulder dislocation |
Wrong outcome |
|
5. |
Three-Dimensional Zero Echo Time Magnetic Resonance Imaging Versus 3-Dimensional Computed Tomography for Glenoid Bone Assessment |
Wrong outcome |
|
6. |
Shoulder joint instability evaluation by CT arthrography and MR arthro graphy |
Wrong outcome |
|
7. |
Assessment of glenoid bone loss and other osseous shoulder pathologies comparing MR-based CT-like images with conventional CT |
Wrong outcome |
|
8. |
Glenoid bone loss measurement in recurrent shoulder dislocation: Assessment of measurement agreement between CT and MRI |
Wrong outcome |
|
9. |
Diagnostic accuracy of MRI in the measurement of glenoid bone loss |
Wrong outcome |
Beoordelingsdatum en geldigheid
Publicatiedatum : 05-06-2026
Beoordeeld op geldigheid : 05-06-2026
Algemene gegevens
De ontwikkeling/herziening van deze richtlijnmodule werd ondersteund door het Kennisinstituut van de Federatie Medisch Specialisten (www.demedischspecialist.nl/kennisinstituut) en werd gefinancierd door de Stichting Kwaliteitsgelden Medisch Specialisten (SKMS). De financier heeft geen enkele invloed gehad op de inhoud van de richtlijnmodule.
Samenstelling werkgroep
Voor het ontwikkelen van de richtlijnmodule is in 2023 een multidisciplinaire werkgroep ingesteld, bestaande uit vertegenwoordigers van alle relevante specialismen (zie hiervoor de Samenstelling van de werkgroep) die betrokken zijn bij de zorg voor patiënten met wervelmetastasen.
Werkgroep
- dr. W. (Walter) Taal (voorzitter), neuroloog Erasmuc MC, Nederlandse Vereniging voor Neurologie
- drs. L. (Lena) van Iterson, AIOS-neuroloog Elisabeth-TweeSteden Ziekenhuis, Nederlandse Vereniging voor Neurologie
- drs. R.P.B. (Robin) Boltjes, neuroloog Antoni van Leeuwenhoek Ziekenhuis, Nederlandse Vereniging voor Neurologie
- Prof. dr. JJ. (Jorrit-Jan) Verlaan, Orthopedisch chirurg UMC Utrecht, Nederlandse Orthopaedische Vereniging
- dr. J. (Jasper) van Tiel, Orthopedisch chirurg UMC Utrecht, Nederlandse Orthopaedische Vereniging
- dr. V. (Vivian) Bongers, Nucleaire geneeskunde Diakonessenhuis Utretch, Nederlandse Vereniging voor Nucleaire Geneeskunde
- Prof. dr. R. (Ronald) Bartels, Neurochirurg Radboudumc, Nederlandse Vereniging voor Neurochirurgie
- dr. S.O. (Selma) Algra, Radioloog UMC Utrecht, Nederlandse Vereniging voor Radiologie
- drs. M.G.A. (Maaike) Schippers, radiotherapeut Instituut Verbeeten, Nederlandse Vereniging voor Radiotherapie en Oncologie
- dr. J.M. (Joanne) van der Velden, radiotherapeut UMC Utrecht, Nederlandse Vereniging voor Radiotherapie en Oncologie
- dr. M.S. (Marthe) Paats, longarts Erasmus MC, Nederlandse Vereniging voor Artsen voor Longziekten en TBC
- dr. P.F. (Paula) Ypma, Internist hematoloog Haga Ziekenhuis, Nederlandse Internisten Vereniging
- dr. F.Y.F.L. (Filip) de Vos, internist-oncoloog en kaderarts palliatieve zorg UMC Utrecht, Nederlandse Internisten Vereniging
- dr. M. (Marije) Vos- van der Hulst, revalidatiearts Sint Maartenskliniek, Nederlandse Vereniging van Revalidatieartsen (vanaf oktober 2025)
- Mevr. S (Silvie) Dronkers†, patiëntvertegenwoordiger, Stichting Darmkanker (tot oktober 2025)
- dr. T.A.R. (Tebbe) Sluis†, Revalidatiearts Rijndam, Nederlandse Vereniging van Revalidatieartsen (tot mei 2025)
Klankbordgroep
- Mevr. Manon Immerzeel, Verpleegkundig specialist Reinier de Graaf ziekenhuis, Verpleegkundigen en Verzorgenden Nederland
- drs. A. (Anita) Ophof, anesthesioloog Antoni van Leeuwenhoek Ziekenhuis, Nederlandse Vereniging voor Anesthesiologie
Met dank aan
- dr. J.H. (Jurgen) Runge, interventieradioloog, UMC Groningen, Nederlandse Vereniging voor Radiologie
Met ondersteuning van
- dr. J. (Josefien) Buddeke, senior adviseur, Kennisinstituut van de Federatie Medisch Specialisten (vanaf juli 2024)
- dr. L. (Linda) Oostendorp, senior adviseur, Kennisinstituut van de Federatie Medisch Specialisten (tot juli 2024)
- drs. B. (Beatrix) Vogelaar, adviseur, Kennisinstituut van de Federatie Medisch Specialisten
- dr. J. (Jing) de Haan-Du, adviseur, Kennisinstituut van de Federatie Medisch Specialisten
- drs. D. (Danique) Middelhuis, adviseur, Kennisinstituut van de Federatie Medisch Specialisten
- drs. A. (Alies) Oost, informatiespecialist, Kennisinstituut van de Federatie Medisch Specialisten
Belangenverklaringen
Een overzicht van de belangen van werkgroepleden en het oordeel over het omgaan met eventuele belangen vindt u in onderstaande tabel. De ondertekende belangenverklaringen zijn op te vragen bij het secretariaat van het Kennisinstituut van de Federatie Medisch Specialisten via secretariaat@kennisinstituut.nl.
Gemelde (neven)functies en belangen werkgroep
|
Naam WERKGROEP |
Hoofdfunctie |
Nevenwerkzaamheden |
Persoonlijke Financiele_Belangen |
Persoonlijke Relaties |
Extern Gefinancierd Onderzoek |
Intellectuele Belangen Reputatie |
Overige Belangen |
Datum |
Acties |
|
Jasper van Tiel |
Orthopedisch chirurg UMC Utrecht en Acibadem IMC |
geen |
geen |
geen |
geen |
geen |
geen |
22-11-2023 |
Geen restrictie |
|
Joanne van der Velden |
Radiotherapeut bij het UMC Utrecht, betaald |
Bestuurslid bij het Landelijk Platform Palliatieve Radiotherapie (NVRO), onbetaald |
Geen |
Geen |
Deelname aan 2 extern gefinancierde onderzoeken, zie onder |
Verwerven van erkenning speelt mee aan mijn deelname aan de werkgroep richtlijn Wervelmetastasen |
Geen overige belangen |
28-12-2023 |
Geen restrictie |
|
Jorrit-Jan Verlaan |
Orthopedisch chirurg, UMC Utrecht (0.4 Fte) |
Lid steering committee AO Spine Knowledge Forum Tumor (onbetaald maar met onkosten vergoeding). |
Hoe de richtlijn wordt vormgegeven staat los van mijn persoonlijke financiële belangen. Er zijn ook geen belangen voor SentryX hoe de richtlijn wordt vormgegeven. |
geen |
Ja. |
Ik heb nationale/internationale expertise/reputatie en een leerstoel op het gebied van de behandeling van wervelmetastasen. Een goed uitgevoerde richtlijn kan helpen deze expertise/reputatie meer exposure te geven maar de impact en eventuele belangenverstrengeling zijn mij onduidelijk. |
geen |
22-11-2023 |
Geen restrictie. Geen penvoerder bij module 'Inschatten overleving'. |
|
Filip de Vos |
Internist-oncoloog en kaderarts palliatieve zorg |
geen |
geen |
geen |
ja |
geen |
BMS Advisory Board; Faculty member ESMO CNS tumors; Quality of Care commission Dutch Society of Medical Oncology; |
20-12-2023 |
Geen restrictie. (In de richtlijn worden geen systemische therapien aanbevolen.) |
|
Maaike Schippers |
Radiotherapeut |
geen |
geen |
geen |
geen |
geen |
geen |
3-12-2023 |
Geen restrictie |
|
Marthe Paats |
Longarts Erasmus MC |
geen |
Geen relevant voor huidige richtlijn. |
geen |
industrie gesponsorde studies lopend in het Erasmus MC waarbij ik lokale PI ben. |
geen |
geen |
26-02-2024 |
Geen restrictie. In de richtlijn worden geen systemische therapien aanbevolen. |
|
Robin Boltjes |
Neuroloog in Antoni van Leeuwenhoek/NKI |
geen |
geen |
nee |
geen |
geen |
nee |
22-11-2023 |
Geen restrictie |
|
Ronald Bartels |
Neurochirurg |
Medisch Adviseur |
geen |
nee |
geen |
net |
geen |
03-04-2024 |
Restrictie ten aanzien van besluitvorming betreffende 'Inschatten overleving'. Vanuit expertise wel meegediscussierd over inhoud van de module, niet betrokken bij het formuleren van de aanbevelingen. |
|
Tebbe Sluis |
revalidatiearts |
geen |
geen |
geen |
geen |
geen |
geen |
11-12-2023 |
Geen restrictie |
|
Vivian Bongers |
MSB Domstad, medisch specialist |
Uitgeverij Prelum, Redacteur tijdschrift IMAGO |
Geen |
Geen |
Geen |
Geen |
Geen |
23-11-2023 |
Geen restrictie |
|
Ypma |
internist hematoloog Hagaziekenhuis den Haag |
geen |
geen |
geen |
Alphabet trial |
geen |
nvt |
04-05-2024 |
Geen restrictie |
|
Van Iterson |
AIOS neurologie |
geen |
geen |
geen |
geen |
geen |
geen |
25-04-2024 |
Geen restrictie |
|
Selma Algra |
Radioloog,St Jansdal Ziekenhuis |
geen |
geen |
geen |
geen |
geen |
geen |
03-09-2024 |
Geen resctrictie |
|
Silvie Dronkers |
Stichting Darmkanker |
geen |
geen |
geen |
geen |
geen |
geen |
06-02-2025 |
Geen restrictie |
|
Walter Taal (voorzitter) |
Neuroloog, Erasmus MC, Rotterdam |
Geen |
Geen |
Geen |
Ja. Alleen op het gebied van neurofibromatose type 1 |
Geen |
Geen |
07-06-2023 |
Geen restrictie |
|
Marije Vos-van der Hulst |
Revalidatie arts, Sint Maartenskliniek Nijmegen |
Voorzitter werkgroep revalidatie artsen dwarslaesie (Nederlands Vlaams dwarslaesie genootschap= werkgroep van de vereniging revalidatieartsen nederland (VRA)) |
geen |
geen |
geen |
geen |
geen |
13-10-2025 |
Geen restrictie |
|
Naam KLANKBORDGROEP |
Hoofdfunctie |
Nevenwerkzaamheden |
Persoonlijke Financiele_Belangen |
Persoonlijke Relaties |
Extern Gefinancierd Onderzoek |
Intellectuele Belangen Reputatie |
Overige Belangen |
Datum |
Acties |
|
Manon Immerzeel |
Deelnemer clusterstuurgroep |
Geen |
Geen |
Geen |
Geen |
Voorzitter in het bestuur van V&VN pijnverpleegkundigen |
Neen |
22-03-2022 |
Geen restrictie |
|
Anita Ophof |
Antoni van Leeuwenhoek Ziekenhuis |
Geen |
Geen |
Geen |
Geen |
Geen |
Geen |
01-05-2025 |
Geen restrictie |
Inbreng patiëntenperspectief
Kwalitatieve raming van mogelijke financiële gevolgen in het kader van de Wkkgz
Bij de richtlijnmodule voerde de werkgroep conform de Wet kwaliteit, klachten en geschillen zorg (Wkkgz) een kwalitatieve raming uit om te beoordelen of de aanbevelingen mogelijk leiden tot substantiële financiële gevolgen. Bij het uitvoeren van deze beoordeling is de richtlijnmodule op verschillende domeinen getoetst (zie het stroomschema bij Werkwijze).
De kwalitatieve raming is toegevoegd aan het einde van elke herziene module.
| Module | Uitkomst raming | Toelichting |
| Diagnosis of epidural expansion | Geen substantiële financiële gevolgen | Hoewel uit de toetsing volgt dat de aanbevelingen breed toepasbaar zijn (5.000-40.000 patiënten), volgt ook uit de toetsing dat het geen nieuwe manier van zorgverlening of andere organisatie van zorgverlening betreft. Er worden daarom geen substantiële financiële gevolgen verwacht. |
Werkwijze
Voor meer details over de gebruikte richtlijnmethodologie verwijzen wij u naar de Werkwijze. Relevante informatie voor de ontwikkeling/herziening van deze richtlijnmodule is hieronder weergegeven.
Zoekverantwoording
Algemene informatie
|
Cluster/richtlijn: NVN wervelmetastasen |
|
|
Uitgangsvraag/modules: UV1 Wat is de diagnostische accuratesse met en zonder MRI bij patiënten met symptomatische wervelmetastasen zichtbaar op bestaande CT? |
|
|
Database(s): Embase.com, Ovid/Medline all |
Datum: 9 april 2025 |
|
Periode: vanaf 2014 |
Talen: geen restrictie |
|
Literatuurspecialist: Alies Oost |
Rayyan: https://new.rayyan.ai/reviews/1403322/screening |
|
BMI-zoekblokken: voor verschillende opdrachten wordt (deels) gebruik gemaakt van de zoekblokken van BMI-Online https://blocks.bmi-online.nl/ |
|
|
Toelichting: Het sleutelartikel wordt gevonden met deze search. |
|
|
Te gebruiken voor richtlijntekst: A systematic literature search was performed by a medical information specialist using the following bibliographic databases: Embase.com and Ovid/Medline all. Both databases were searched from 2014 to April 9th, 2025 for systematic reviews, RCTs and observational studies. Systematic searches were completed using a combination of controlled vocabulary and natural language keywords. The overall search strategy was derived from three primary search concepts: (1) spine metastasis; (2) CT AND MRI; (3) diagnostic accuracy. Duplicates were removed using EndNote software. After deduplication a total of 376 records were imported for title/abstract screening. |
|
Zoekopbrengst
|
|
EMBASE |
OVID/MEDLINE |
Ontdubbeld |
|
SR |
44 |
6 |
45 |
|
RCT |
60 |
10 |
65 |
|
Observationele studies |
247 |
62 |
266 |
|
Totaal |
351 |
78 |
376* |
*in Rayyan
Zoekstrategie
Embase.com
|
No. |
Query |
Results |
|
#1 |
'spine metastasis'/exp OR 'spinal cord metastasis'/exp OR 'cervical lymph node metastasis'/exp OR (('spinal cord tumor'/exp OR 'spine tumor'/exp OR 'spinal cord compression'/exp OR (((spinal* OR medulla*) NEAR/3 (compress* OR impingement OR pinch*)):ti,ab,kw)) AND ('metastasis'/de OR 'bone metastasis'/de OR metasta*:ti,ab,kw OR oligometasta*:ti,ab,kw OR micrometasta*:ti,ab,kw OR (((neoplas* OR carcinoma OR cancer* OR malignan* OR tumor* OR tumour*) NEAR/4 (dissemination OR disseminated OR spread* OR secondary OR migrat* OR seed*)):ti,ab,kw))) OR (((spine* OR spinal* OR intraspinal OR vertebr* OR 'cauda equina' OR cervicothoracic OR cord* OR coccyx OR duralsac* OR 'dural sac*' OR epidural OR extradural OR 'extra dural' OR intervertebr* OR lumbar OR lumbosac* OR 'lumbo sac*' OR orthothoracic OR sacral OR sacrum OR 'thecal sac*' OR thoracolumbar OR odontoid OR 'anterior horn' OR 'posterior horn' OR 'extrapyramidal tract*' OR 'pyramidal tract*' OR 'substantia gelatinosa' OR 'spinothalamic tract*') NEAR/4 (metast* OR oligometast* OR micrometast*)):ti,ab,kw) OR ((cervical*:ti,ab,kw OR medulla*:ti,ab,kw OR intramedulla*:ti,ab,kw OR thoracic:ti,ab,kw) AND (spine*:ti,ab,kw OR spinal*:ti,ab,kw OR intraspinal:ti,ab,kw OR vertebr*:ti,ab,kw OR intervertebr*:ti,ab,kw OR lumbar:ti,ab,kw) AND (metast*:ti,ab,kw OR oligometast*:ti,ab,kw OR micrometast*:ti,ab,kw)) OR mescc:ti,ab,kw OR mscc:ti,ab,kw |
30633 |
|
#2 |
('computer assisted tomography'/exp OR 'ct scanner'/de OR 'cat scan*':ti,ab,kw OR ((compute* NEAR/3 tomograph*):ti,ab,kw) OR ct:ti,ab,kw OR cts:ti,ab,kw) AND ('nuclear magnetic resonance imaging'/exp OR 'mri scanner'/exp OR ('magnetic resonance':ab,ti AND (image:ab,ti OR images:ab,ti OR imaging:ab,ti)) OR mri:ab,ti OR mris:ab,ti OR nmr:ab,ti OR mra:ab,ti OR mras:ab,ti OR zeugmatograph*:ab,ti OR 'mr tomography':ab,ti OR 'mr tomographies':ab,ti OR 'mr tomographic':ab,ti OR 'mr imag*':ti,ab,kw OR 'proton spin':ab,ti OR ((magneti*:ab,ti OR 'chemical shift':ab,ti) AND imaging:ab,ti) OR fmri:ab,ti OR fmris:ab,ti OR rsfmri:ti,ab,kw) |
473119 |
|
#3 |
'sensitivity and specificity'/de OR sensitivity:ab,ti OR specificity:ab,ti OR predict*:ab,ti OR 'roc curve':ab,ti OR 'receiver operator':ab,ti OR 'receiver operators':ab,ti OR likelihood:ab,ti OR 'diagnostic error'/exp OR 'diagnostic accuracy'/exp OR 'diagnostic test accuracy study'/exp OR 'inter observer':ab,ti OR 'intra observer':ab,ti OR interobserver:ab,ti OR intraobserver:ab,ti OR validity:ab,ti OR kappa:ab,ti OR reliability:ab,ti OR reproducibility:ab,ti OR ((test NEAR/2 're-test'):ab,ti) OR ((test NEAR/2 'retest'):ab,ti) OR 'reproducibility'/exp OR accuracy:ab,ti OR 'differential diagnosis'/exp OR 'validation study'/de OR 'measurement precision'/exp OR 'diagnostic value'/exp OR 'reliability'/exp OR 'predictive value'/exp OR ppv:ti,ab,kw OR npv:ti,ab,kw OR (((false OR true) NEAR/3 (negative OR positive)):ti,ab) |
6816193 |
|
#4 |
#1 AND #2 AND #3 NOT ('conference abstract'/it OR 'editorial'/it OR 'letter'/it OR 'note'/it) NOT (('animal'/exp OR 'animal experiment'/exp OR 'animal model'/exp OR 'nonhuman'/exp) NOT 'human'/exp) |
1055 |
|
#5 |
#4 AND [2014-2025]/py |
652 |
|
#6 |
'meta analysis'/exp OR 'meta analysis (topic)'/exp OR 'systematic review'/exp OR 'systematic review (topic)'/exp OR 'scoping review'/exp OR 'rapid review'/exp OR 'umbrella review'/exp OR 'cochrane database of systematic reviews'/jt OR 'network meta-analysis'/exp OR 'networkmeta analy*':ti,ab,kw OR 'networkmetaanaly*':ti,ab,kw OR metaanaly*:ti,ab,kw OR 'meta analy*':ti,ab,kw OR metanaly*:ti,ab,kw OR prisma:ti,ab,kw OR prospero:ti,ab,kw OR metaanali*:ti,ab,kw OR 'meta anali*':ti,ab,kw OR metanali*:ti,ab,kw OR (((systemati* OR scoping OR umbrella OR 'structured literature') NEAR/3 (review* OR overview*)):ti,ab,kw) OR (((structured OR systemic*) NEAR/3 (review* OR overview* OR synth*) NEAR/3 literature):ti,ab,kw) OR ((systemic* NEAR/1 review*):ti,ab,kw) OR (((systemati* OR literature OR database* OR 'data base*') NEAR/10 search*):ti,ab,kw) OR (((structured OR comprehensive* OR systemic*) NEAR/3 search*):ti,ab,kw) OR (((literature NEAR/3 (review* OR overview*)):ti,ab,kw) AND (search*:ti,ab,kw OR database*:ti,ab,kw OR 'data base*':ti,ab,kw)) OR (('data extraction*':ti,ab,kw OR 'data source*':ti,ab,kw) AND ('study selection*':ti,ab,kw OR 'studies selection*':ti,ab,kw)) OR ('search strateg*':ti,ab,kw AND 'selection criteria*':ti,ab,kw) OR ('data source*':ti,ab,kw AND 'data synth*':ti,ab,kw) OR medline*:ti,ab,kw OR pubmed*:ti,ab,kw OR 'pub med*':ti,ab,kw OR embase:ti,ab,kw OR cochrane*:ti,ab,kw OR (((critical* OR rapid*) NEAR/2 (review* OR overview* OR synth*)):ti) OR ((((critical* OR rapid*) NEAR/3 (review* OR overview* OR synth*)):ab) AND (search*:ab OR database*:ab OR 'data base*':ab)) OR metasynth*:ti,ab,kw OR 'meta synth*':ti,ab,kw OR 'review* of review*':ti,ab,kw |
1140993 |
|
#7 |
'clinical trial'/exp OR 'randomization'/exp OR 'single blind procedure'/exp OR 'double blind procedure'/exp OR 'crossover procedure'/exp OR 'placebo'/exp OR 'prospective study'/exp OR rct:ab,ti OR random*:ab,ti OR 'single blind':ab,ti OR 'randomized controlled trial'/exp OR placebo*:ab,ti |
4248096 |
|
#8 |
'major clinical study'/de OR 'clinical study'/de OR 'family study'/de OR 'longitudinal study'/de OR 'retrospective study'/de OR 'prospective study'/de OR 'cohort analysis'/de OR 'case control study'/de OR 'comparative study'/exp OR 'control group'/de OR 'controlled study'/de OR 'controlled clinical trial'/de OR 'crossover procedure'/de OR 'double blind procedure'/de OR 'phase 2 clinical trial'/de OR 'phase 3 clinical trial'/de OR 'phase 4 clinical trial'/de OR 'pretest posttest design'/de OR 'pretest posttest control group design'/de OR 'quasi experimental study'/de OR 'single blind procedure'/de OR 'triple blind procedure'/de OR ((cohort NEAR/1 (study OR studies)):ab,ti) OR (('case control' NEAR/1 (study OR studies)):ab,ti) OR (('follow up' NEAR/1 (study OR studies)):ab,ti) OR (observational NEAR/1 (study OR studies)) OR ((epidemiologic NEAR/1 (study OR studies)):ab,ti) OR (('cross sectional' NEAR/1 (study OR studies)):ab,ti) OR (((control OR controlled) NEAR/6 trial):ti,ab,kw) OR (((control OR controlled) NEAR/6 (study OR studies)):ti,ab,kw) OR (((control OR controlled) NEAR/1 active):ti,ab,kw) OR 'open label*':ti,ab,kw OR (((double OR two OR three OR multi OR trial) NEAR/1 (arm OR arms)):ti,ab,kw) OR ((allocat* NEAR/10 (arm OR arms)):ti,ab,kw) OR placebo*:ti,ab,kw OR 'sham-control*':ti,ab,kw OR (((single OR double OR triple OR assessor) NEAR/1 (blind* OR masked)):ti,ab,kw) OR nonrandom*:ti,ab,kw OR 'non-random*':ti,ab,kw OR 'quasi-experiment*':ti,ab,kw OR crossover:ti,ab,kw OR 'cross over':ti,ab,kw OR 'parallel group*':ti,ab,kw OR 'factorial trial':ti,ab,kw OR ((phase NEAR/5 (study OR trial)):ti,ab,kw) OR ((case* NEAR/6 (matched OR control*)):ti,ab,kw) OR ((match* NEAR/6 (pair OR pairs OR cohort* OR control* OR group* OR healthy OR age OR sex OR gender OR patient* OR subject* OR participant*)):ti,ab,kw) OR ((propensity NEAR/6 (scor* OR match*)):ti,ab,kw) OR versus:ti OR vs:ti OR compar*:ti OR ((compar* NEAR/1 study):ti,ab,kw) OR (('observational study'/de OR 'cross-sectional study'/de OR 'multicenter study'/de OR 'correlational study'/de OR 'follow up'/de OR cohort*:ti,ab,kw OR 'follow up':ti,ab,kw OR followup:ti,ab,kw OR longitudinal*:ti,ab,kw OR prospective*:ti,ab,kw OR retrospective*:ti,ab,kw OR observational*:ti,ab,kw OR 'cross sectional*':ti,ab,kw OR cross?ectional*:ti,ab,kw OR multicent*:ti,ab,kw OR 'multi-cent*':ti,ab,kw OR consecutive*:ti,ab,kw) AND (group:ti,ab,kw OR groups:ti,ab,kw OR subgroup*:ti,ab,kw OR versus:ti,ab,kw OR vs:ti,ab,kw OR compar*:ti,ab,kw OR 'odds ratio*':ab OR 'relative odds':ab OR 'risk ratio*':ab OR 'relative risk*':ab OR 'rate ratio':ab OR aor:ab OR arr:ab OR rrr:ab OR ((('or' OR 'rr') NEAR/6 ci):ab))) |
17985308 |
|
#9 |
#5 AND #6 |
44 |
|
#10 |
#5 AND #7 NOT #9 |
60 |
|
#11 |
#5 AND #8 NOT (#9 OR #10) |
247 |
|
#12 |
#9 OR #10 OR #11 |
351 |
Ovid/Medline
|
# |
Searches |
Results |
|
1 |
((exp Spinal Neoplasms/ or exp Spinal Cord Neoplasms/ or exp Spinal Cord Compression/ or ((spinal* or medulla*) adj3 (compress* or impingement or pinch*)).ti,ab,kf.) and (exp Neoplasm Metastasis/ or metasta*.ti,ab,kf. or oligometasta*.ti,ab,kf. or micrometasta*.ti,ab,kf. or ((neoplas* or carcinoma or cancer* or malignan* or tumor* or tumour*) adj4 (dissemination or disseminated or spread* or secondary or migrat* or seed*)).ti,ab,kf.)) or ((spine* or spinal* or intraspinal or vertebr* or 'cauda equina' or cervicothoracic or cord* or coccyx or duralsac* or 'dural sac*' or epidural or extradural or 'extra dural' or intervertebr* or lumbar or lumbosac* or 'lumbo sac*' or orthothoracic or sacral or sacrum or 'thecal sac*' or thoracolumbar or odontoid or "Anterior Horn" or "Posterior Horn" or "Extrapyramidal Tract*" or "Pyramidal Tract*" or "Substantia Gelatinosa" or "Spinothalamic Tract*") adj4 (metast* or oligometast* or micrometast*)).ti,ab,kf. or ((cervical* or medulla* or intramedulla* or thoracic) and (spine* or spinal* or intraspinal or vertebr* or intervertebr* or lumbar) and (metast* or oligometast* or micrometast*)).ti,ab,kf. or mescc.ti,ab,kf. or mscc.ti,ab,kf. |
15675 |
|
2 |
(exp Tomography, X-Ray Computed/ or exp Tomography Scanners, X-Ray Computed/ or 'cat scan*'.ti,ab,kf. or (compute* adj3 tomograph*).ti,ab,kf. or ct.ti,ab,kf. or cts.ti,ab,kf.) and (exp magnetic resonance imaging/ or ("magnetic resonance" and (image or images or imaging)).ti,ab,kf. or mri.ti,ab,kf. or mris.ti,ab,kf. or nmr.ti,ab,kf. or mra.ti,ab,kf. or mras.ti,ab,kf. or zeugmatograph*.ti,ab,kf. or "mr tomography".ti,ab,kf. or "mr tomographies".ti,ab,kf. or "mr tomographic".ti,ab,kf. or 'mr imag*'.ti,ab,kf. or "proton spin".ti,ab,kf. or ((magneti* or "chemical shift") and imaging).ti,ab,kf. or fmri.ti,ab,kf. or fmris.ti,ab,kf. or rsfmri.ti,ab,kf.) |
170795 |
|
3 |
exp "Sensitivity and Specificity"/ or (sensitivity or specificity).ti,ab. or (predict* or ROC-curve or receiver-operator*).ti,ab. or (likelihood or LR*).ti,ab. or exp Diagnostic Errors/ or (inter-observer or intra-observer or interobserver or intraobserver or validity or kappa or reliability).ti,ab. or reproducibility.ti,ab. or (test adj2 (re-test or retest)).ti,ab. or "Reproducibility of Results"/ or accuracy.ti,ab. or Diagnosis, Differential/ or Validation Study/ or ((false or true) adj3 (negative or positive)).ti,ab. |
5378065 |
|
4 |
(1 and 2 and 3) not (comment/ or editorial/ or letter/) not ((exp animals/ or exp models, animal/) not humans/) |
370 |
|
5 |
limit 4 to yr="2014 -Current" |
152 |
|
6 |
exp Meta-Analysis/ or exp "Meta-Analysis as Topic"/ or exp Network Meta-Analysis/ or exp Systematic Review/ or exp "Systematic Reviews as Topic"/ or (networkmeta analy* or networkmetaanaly* or metaanaly* or meta analy* or metanaly* or prisma or prospero or metaanali* or meta anali* or metanali*).ti,ab,kf. or ((systemati* or scoping or umbrella or structured literature) adj3 (review* or overview*)).ti,ab,kf. or ((structured or systemic*) adj3 (review* or overview* or synth*) adj3 literature).ti,ab,kf. or (systemic* adj1 review*).ti,ab,kf. or ((systemati* or literature or database* or data base*) adj10 search*).ti,ab,kf. or ((structured or comprehensive* or systemic*) adj3 search*).ti,ab,kf. or ((literature adj3 (review* or overview*)) and (search* or database* or data base*)).ti,ab,kf. or ((data extraction* or data source*) and (study selection* or studies selection*)).ti,ab,kf. or (search strateg* and selection criteria*).ti,ab,kf. or (data source* and data synth*).ti,ab,kf. or (medline* or pubmed* or pub med* or embase or cochrane*).ti,ab,kf. or cochrane.jw. or ((critical* or rapid*) adj2 (review* or overview* or synth*)).ti. or (((critical* or rapid*) adj3 (review* or overview* or synth*)) and (search* or database* or data base*)).ab. or metasynth*.ti,ab,kf. or meta synth*.ti,ab,kf. |
824916 |
|
7 |
exp clinical trial/ or randomized controlled trial/ or exp clinical trials as topic/ or randomized controlled trials as topic/ or Random Allocation/ or Double-Blind Method/ or Single-Blind Method/ or (clinical trial, phase i or clinical trial, phase ii or clinical trial, phase iii or clinical trial, phase iv or controlled clinical trial or randomized controlled trial or multicenter study or clinical trial).pt. or random*.ti,ab. or (clinic* adj trial*).tw. or ((singl* or doubl* or treb* or tripl*) adj (blind$3 or mask$3)).tw. or Placebos/ or placebo*.tw. |
2867049 |
|
8 |
Case-control Studies/ or clinical trial, phase ii/ or clinical trial, phase iii/ or clinical trial, phase iv/ or comparative study/ or control groups/ or controlled before-after studies/ or controlled clinical trial/ or double-blind method/ or historically controlled study/ or matched-pair analysis/ or single-blind method/ or (((control or controlled) adj6 (study or studies or trial)) or (compar* adj (study or studies)) or ((control or controlled) adj1 active) or "open label*" or ((double or two or three or multi or trial) adj (arm or arms)) or (allocat* adj10 (arm or arms)) or placebo* or "sham-control*" or ((single or double or triple or assessor) adj1 (blind* or masked)) or nonrandom* or "non-random*" or "quasi-experiment*" or "parallel group*" or "factorial trial" or "pretest posttest" or (phase adj5 (study or trial)) or (case* adj6 (matched or control*)) or (match* adj6 (pair or pairs or cohort* or control* or group* or healthy or age or sex or gender or patient* or subject* or participant*)) or (propensity adj6 (scor* or match*))).ti,ab,kf. or (confounding adj6 adjust*).ti,ab. or (versus or vs or compar*).ti. or exp cohort studies/ or epidemiologic studies/ or ((multicenter study/ or observational study/ or seroepidemiologic studies/ or (cohort* or 'follow up' or followup or longitudinal* or prospective* or retrospective* or observational* or multicent* or 'multi-cent*' or consecutive*).ti,ab,kf.) and ((group or groups or subgroup* or versus or vs or compar*).ti,ab,kf. or ('odds ratio*' or 'relative odds' or 'risk ratio*' or 'relative risk*' or aor or arr or rrr).ab. or (("OR" or "RR") adj6 CI).ab.)) or Case control.tw. or cohort.tw. or Cohort analy$.tw. or (Follow up adj (study or studies)).tw. or (observational adj (study or studies)).tw. or Longitudinal.tw. or Retrospective*.tw. or prospective*.tw. or consecutive*.tw. or Cross sectional.tw. or Cross-sectional studies/ or historically controlled study/ or interrupted time series analysis/ |
7975729 |
|
9 |
5 and 6 |
6 |
|
10 |
(5 and 7) not 9 |
10 |
|
11 |
(5 and 8) not (9 or 10) |
62 |
|
12 |
9 or 10 or 11 |
78 |