1. Home
  2. Diagnostic Tests

Diagnostic Tests

Diagnostic Accuracy of Symptoms, Physical Signs, and Laboratory Tests for Giant Cell Arteritis: A Systematic Review and Meta-analysis

Author/s: 
van der Geest, Kornelis S. M., Sandovici , S., Brouwer, Elisabeth, Mackie, S.L.

Abstract

Importance: Current clinical guidelines recommend selecting diagnostic tests for giant cell arteritis (GCA) based on pretest probability that the disease is present, but how pretest probability should be estimated remains unclear.

Objective: To evaluate the diagnostic accuracy of symptoms, physical signs, and laboratory tests for suspected GCA.

Data sources: PubMed, EMBASE, and the Cochrane Database of Systematic Reviews were searched from November 1940 through April 5, 2020.

Study selection: Trials and observational studies describing patients with suspected GCA, using an appropriate reference standard for GCA (temporal artery biopsy, imaging test, or clinical diagnosis), and with available data for at least 1 symptom, physical sign, or laboratory test.

Data extraction and synthesis: Screening, full text review, quality assessment, and data extraction by 2 investigators. Diagnostic test meta-analysis used a bivariate model.

Main outcome(s) and measures: Diagnostic accuracy parameters, including positive and negative likelihood ratios (LRs).

Results: In 68 unique studies (14 037 unique patients with suspected GCA; of 7798 patients with sex reported, 5193 were women [66.6%]), findings associated with a diagnosis of GCA included limb claudication (positive LR, 6.01; 95% CI, 1.38-26.16), jaw claudication (positive LR, 4.90; 95% CI, 3.74-6.41), temporal artery thickening (positive LR, 4.70; 95% CI, 2.65-8.33), temporal artery loss of pulse (positive LR, 3.25; 95% CI, 2.49-4.23), platelet count of greater than 400 × 103/μL (positive LR, 3.75; 95% CI, 2.12-6.64), temporal tenderness (positive LR, 3.14; 95% CI, 1.14-8.65), and erythrocyte sedimentation rate greater than 100 mm/h (positive LR, 3.11; 95% CI, 1.43-6.78). Findings that were associated with absence of GCA included the absence of erythrocyte sedimentation rate of greater than 40 mm/h (negative LR, 0.18; 95% CI, 0.08-0.44), absence of C-reactive protein level of 2.5 mg/dL or more (negative LR, 0.38; 95% CI, 0.25-0.59), and absence of age over 70 years (negative LR, 0.48; 95% CI, 0.27-0.86).

Conclusions and relevance: This study identifies the clinical and laboratory features that are most informative for a diagnosis of GCA, although no single feature was strong enough to confirm or refute the diagnosis if taken alone. Combinations of these symptoms might help direct further investigation, such as vascular imaging, temporal artery biopsy, or seeking evaluation for alternative diagnoses.

The Potential Emergence of Disease-Modifying Treatments for Alzheimer Disease: The Role of Primary Care in Managing the Patient Journey

Author/s: 
Lam, J., Hlávka, J., Mattke, S.

Despite recent setbacks, disease-modifying treatments (DMTs) for Alzheimer disease (AD) might become available within a few years. These DMTs are likely to be used in the early stages of AD to avoid the progression to manifest dementia, which implies that a large reservoir of prevalent cases would need to be evaluated when DMTs first become available. Primary care providers (PCPs) would play a vital role in managing the patient flow to specialty care. We review the literature on diagnostic tests that could be used by PCPs and estimate the impact of different testing approaches on demand for specialty care.While many tests have been evaluated, only the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA) perform acceptably for detection of early-stage cognitive decline with sensitivities and specificities of 55% to 82% and 72% to 84%, respectively, for the MMSE; and 77% to 96% and 73% to 95%, respectively, for the MoCA. However, neither test is sufficiently specific for the AD pathology and would result in 4 to 5 false positives for each true positive. Blood-based tests for AD biomarkers may soon become available for clinical use. A plasma amyloid-β (Aβ) test has been shown to have a sensitivity of up to 97% and specificity of up to 81%. Adding this test to the MMSE or MoCA could reduce false positives by approximately 80%.These findings suggest a combination of brief cognitive tests and blood-based biomarker tests will allow PCPs to identify patients with potential early stage AD efficiently and triage them for further evaluation.

Keywords 
Alzheimer Disease

Coronary Microvascular Dysfunction Causing Cardiac Ischemia in Women

Author/s: 
Wei, J, Cheng, S, Merz, CNB

Two-thirds of women who present with persistent symptoms and clinical signs of ischemia have no evidence of obstructive coronary artery disease (INOCA) on angiography. Cardiac ischemia can be manifested by chest discomfort, shortness of breath, decreased exercise tolerance, and ST-segment or imaging abnormalities at rest or with stress. Although women with a clinical presentation suggesting ischemic heart disease are often reassured after having a “normal” angiogram that their symptoms are not likely cardiac in etiology, 1 in 13 of these women die from a cardiac cause within 10 years of the angiographic evaluation, and the most frequent adverse cardiac event is hospitalization for heart failure with preserved ejection fraction with an observed 10-fold higher rate compared with asymptomatic women (3.3% vs 0.3%). For these women with INOCA, clinicians should consider the important, yet often overlooked, diagnosis of coronary microvascular dysfunction (CMD)—a small vessel disorder that confers an adverse prognosis in women for which there are available and continuously evolving diagnostic and treatment strategies.

Keywords 
coronary microvascular dysfunction CMD obstructive coronary artery disease cardiac ischemia females angina

The Many Faces of Cobalamin (Vitamin B12) Deficiency

Author/s: 
Wolffenbuttel, Bruce, Wouters, Hanneke J.C.M., Heiner-Fokkema, Rebecca, van der Klauw, Melanie M.

Although cobalamin (vitamin B12) deficiency was described over a century ago, it is still difficult toestablish the correct diagnosis and prescribe the right treatment. Symptoms related to vitamin B12 deficiency may be diverse and vary from neurologic to psychiatric. A number of individuals with vitamin B12 deficiency may present with the classic megaloblastic anemia.
In clinical practice, many cases of vitamin B12 deficiency are overlooked or sometimes even misdiagnosed. In this review, we describe the heterogeneous disease spectrum of patients with vitamin B12 deficiency in whom the diagnosis was either based on low serum B12 levels, elevated biomarkers like methylmalonic acid and/or homocysteine, or the improvement of clinical symptoms after the institution of parenteral vitamin B12 therapy. We discuss the possible clinical signs and symptoms of patients with B12 deficiency and the various pitfalls of diagnosis and treatment.

Keywords 
Vitamin B 12 Biomarkers diagnosis

The Many Faces of Cobalamin (Vitamin B12) Deficiency

Author/s: 
Wolffenbuttel, Bruce, Wouters, Hanneke J.C.M., Heiner-Fokkema, Rebecca, van der Klauw, Melanie M.

Although cobalamin (vitamin B12) deficiency was described over a century ago, it is still difficult toestablish the correct diagnosis and prescribe the right treatment. Symptoms related to vitamin B12 deficiency may be diverse and vary from neurologic to psychiatric. A number of individuals with vitamin B12 deficiency may present with the classic megaloblastic anemia.
In clinical practice, many cases of vitamin B12 deficiency are overlooked or sometimes even misdiagnosed. In this review, we describe the heterogeneous disease spectrum of patients with vitamin B12 deficiency in whom the diagnosis was either based on low serum B12 levels, elevated biomarkers like methylmalonic acid and/or homocysteine, or the improvement of clinical symptoms after the institution of parenteral vitamin B12 therapy. We discuss the possible clinical signs and symptoms of patients with B12 deficiency and the various pitfalls of diagnosis and treatment.

Keywords 
Vitamin B 12 Biomarkers diagnosis

Clinically Diagnosing Pertussis-associated Cough in Adults and Children: CHEST Guideline and Expert Panel Report

Author/s: 
Moore, Abigail, Harnden, Anthony, Grant, Cameron C., Patel, Sheena, Irwin, Richard S.

BACKGROUND:

The decision to treat a suspected case of pertussis with antibiotics is usually based on a clinical diagnosis rather than waiting for laboratory confirmation. The current guideline focuses on making the clinical diagnosis of pertussis-associated cough in adults and children.

METHODS:

The American College of Chest Physicians (CHEST) methodologic guidelines and the Grading of Recommendations, Assessment, Development, and Evaluation framework were used. The Expert Cough Panel based their recommendations on findings from a systematicreview that was recently published on the topic; final grading was reached by consensus according to Delphi methodology. The systematic review was carried out to answer the Key Clinical Question: In patients presenting with cough, how can we most accurately diagnose from clinical features alone those who have pertussis-associated cough as opposed to other causes of cough?

RESULTS:

In adults, after pre-specified meta-analysis exclusions, pooled estimates of sensitivity and specificity were generated for only 4 clinical features: paroxysmal cough, post-tussive vomiting, inspiratory whooping, and absence of fever. Both paroxysmal cough and absence of fever had high sensitivity (93.2% [95% CI, 83.2-97.4] and 81.8% [95% CI, 72.2-88.7], respectively) and low specificity (20.6% [95% CI, 14.7-28.1] and 18.8% [95% CI, 8.1-37.9]). Inspiratory whooping and posttussive vomiting had a low sensitivity (32.5% [95% CI, 24.5-41.6] and 29.8% [95% CI, 18.0-45.2]) but high specificity (77.7% [95% CI, 73.1-81.7] and 79.5% [95% CI, 69.4-86.9]). In children, after pre-specified meta-analysis exclusions, pooled estimates of sensitivity and specificity were generated for only 1 clinical feature in children (0-18 years): posttussive vomiting. Posttussive vomiting in children was only moderately sensitive (60.0% [95% CI, 40.3-77.0]) and specific (66.0% [95% CI, 52.5-77.3]).

CONCLUSIONS:

In adults with acute (< 3 weeks) or subacute (3-8 weeks) cough, the presence of whooping or posttussive vomiting should rule in a possible diagnosis of pertussis, whereas the lack of a paroxysmal cough or the presence of fever should rule it out. In children with acute (< 4 weeks) cough, posttussive vomiting is suggestive of pertussis but is much less helpful as a clinical diagnostic test. Guideline suggestions are made based upon these findings and conclusions.

Keywords 
cough evidence-based medicine guidelines infectious disease diagnosis
Subscribe to Diagnostic Tests