Diagnosing Pulmonary Embolism in the Context of Common Alternative Diagnoses in primary care

Clinical decision rules (CDRs) and D-dimer testing are available for general
practitioners (GPs) to distinguish pulmonary embolism (PE) from common
alternative cardiopulmonary diagnoses in patients with shortness of breath.
However, D-dimer testing is often falsely elevated, leading to unneeded, costly
and potential harmful referrals for CT pulmonary angiography (CTPA). To
alleviate this problem, a risk-tailored diagnostic approach was recently tested
and validated with good results in secondary care: the YEARS-strategy. In this
strategy, the physician scores three clinical items: (i) haemoptysis, (ii)
clinical signs suggestive of deep venous thrombosis, and (iii) PE considered
most likely diagnosis by the physician. If none of these items is present, a
D-dimer threshold of 1000 mcg/L is applied, while if one or more items are
present, the *classical* threshold of 500 mcg/L is used. If a suspected patient
is below either D-dimer threshold, PE is safely ruled out (i.e. a negative
YEARS-strategy and thus no recommendation for referral for CTPA). In secondary
care, this algorithm leads to an absolute reduction of 14% of CTPA*s with a
completely similar safety (only 0.4% missed PE cases), as compared to a fixed
D-dimer threshold of 500 mcg/L. Currently, this approach is therefore
considered standard-of-care in order to rule-out PE on emergency wards in the
Netherlands. This strategy however is not yet implemented in primary care, and
awaits validation in this healthcare setting.

Our primary objective is to prospectively implement and validate the YEARS
strategy in primary care. Secondary objectives are, (i) to quantify the added
diagnostic value of C-reactive protein (CRP) to a clinical assessment and
D-dimer testing in order to enhance distinguishing PE from a pneumonia, (ii) to
develop a polytomous logistic model for estimating the diagnostic probability
of both PE and, and (iii) to statistically quantify predictors for assessing PE
as most likely diagnosis by GPs.

Prospective diagnostic cohort study.

Using a clinical decision rule, D-dimer testing and subsequently decide on the
appropriate referral decisions depending on those outcomes, is worldwide
routine clinical practice and based upon current (inter)national guidelines.
The YEARS-strategy is a variation (or updating) of such a decision model guided
diagnostic strategy. Accordingly, there is not a true related harm to
participating in this study for validation of this YEARS strategy. In addition,
a novel aspect of this study is the additional point of care (POC) CRP testing
simultaneously with D-dimer testing. An important advantage of this POC test,
is the ability of the GP to better and earlier discriminate between the
presence of PE or the most common alternative diagnosis (namely pneumonia) and
thus manage PE suspected patients more accurately. Previous research showed
that the YEARS strategy is safe in a secondary care setting with 14% fewer
referrals for CTPA and consequently applying the YEARS-strategy is now
standard-of-care in (many) emergency wards in the Netherlands (including the
UMC Utrecht). Alongside patient accrual into the study, we will evaluate study
findings (notably the implementation safety), on a regular basis using
pre-specified stopping rules (see chapter 9). Furthermore, a decrease of CTPA*s
will lead to less exposure to radiation, potential allergic reactions to
contrast material, contrast-induced nephropathy and healthcare costs. Finally,
a decrease of referrals to secondary care results in less burden and insecurity
in those patients. Both can be considered as benefits for participating into
this study.