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Reduce unnecessary routine vitamin D testing

Author/s: 
Singer, Alexander G., McChesney, Christopher

Laura is a 40-year-old engineer of eastern European ancestry who presents to your office to request testing of her vitamin D levels. She generally wears sunscreen in the summer and wears sun-protective clothing year round. She is fairly healthy, eating a balanced diet high in fresh fruits and vegetables, but experiences migraines for which she takes triptans for rescue about 4 times per year. She and her partner own a house in a middle-class neighbourhood where they live with their son. Laura informs you that her mother has been taking vitamin D supplements for many years based on her doctor’s recommendations to improve her bone health. Additionally, Laura tells you that her neighbour, a nurse about her age, recently had her vitamin D levels checked and they were “very low,” so she has considered starting vitamin D supplementation.

Laura is hoping that by testing her vitamin D levels she will know how much supplementation she needs to take to protect her from COVID-19, cancer, and fractures as she gets older. Laura is worried that her levels might be low because she avoids direct sunlight and is concerned that she may be missing an easy opportunity to improve her health with supplementation she can afford.

Keywords 
vitamin D vitamins

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

Diagnosis, Prevention, and Treatment of C. difficile: Current State of the Evidence

Author/s: 
Butler, M., Olson A., Drekonja, D., Shaukat, A., Schwehr, N., Shippee, N., Wilt, TJ

Focus

This is a summary of a systematic review that evaluated the recent evidence regarding the accuracy of diagnostic tests and the effectiveness of interventions for preventing and treating Clostridium difficile (C. difficile) infection. The systematic review included 93 articles published between 2010 and April 2015. This summary is provided to assist in informed clinical decisionmaking. However, reviews of evidence should not be construed to represent clinical recommendations or guidelines.

Background

C. difficile is a Gram-positive, anaerobic, spore-forming bacterium generally acquired through ingestion. Symptoms of C. difficile infection (CDI) can range from mild diarrhea to severe conditions such as pseudomembranous colitis and toxic megacolon that can result in death. The estimated mortality rate for health care-associated CDI ranged from 2.4 to 8.9 deaths per 100,000 in 2011. For people ≥65 years of age, the mortality rate was 55.1 deaths per 100,000.

Effective containment and treatment of CDI depends on accurate and swift diagnosis. CDI is diagnosed using clinical findings and tests such as: (1) nucleic acid amplification using loop-mediated isothermal amplification (LAMP) and the polymerase chain reaction (PCR), (2) tests for disease- generating C. difficile toxins (including immunoassays), and (3) test algorithms (these are two-step procedures: the first step is a fast screen for the presence of the organism using a test such as the glutamate dehydrogenase [GDH] assay; if the first test is positive, a second test for toxins is performed).

Efforts to prevent CDI include antimicrobial stewardship, the use of infection-control strategies such as handwashing, and immune-boosting strategies. Antimicrobial stewardship is a coordinated program that promotes the appropriate use of antimicrobials to reduce microbial resistance and decrease the spread of infections. Handwashing with soap and water is helpful for removing C. difficile spores, which are resistant to alcohol rubs or hand sanitizer. Measures that improve a patient's immune defenses include the use of probiotics to promote healthy gut flora and the maintenance of balanced nutrition.

Initial treatment of CDI commonly involves the use of oral antimicrobials such as metronidazole and vancomycin. Mild to moderate initial CDI is often treated with metronidazole, while severe initial CDI is often treated with vancomycin. Treatment with metronidazole and vancomycin can be problematic, however, as they have been implicated in the development of vancomycin-resistant enterococci in immunocompromised patients.

CDI recurs in 15 to 35 percent of patients who have had one previous episode and in 33 to 65 percent of patients who have had more than two previous episodes. Diagnosis and treatment of relapsed or recurrent CDI are challenging. Diagnosis of recurrent CDI is based on the recurrence of clinical symptoms, and repeat testing may not be required. Currently, clinicians choose from a variety of antimicrobials, dosing protocols, and adjunctive treatments (such as probiotics and fecal microbiota transplantation [FMT]) to manage relapsed or recurrent CDI.

The current review aimed to update a 2011 review regarding the accuracy of CDI diagnostic tests and the effects of interventions to prevent and treat CDI in adults.

Conclusions

Diagnosis of CDI: Nucleic acid amplification tests have high sensitivity and specificity for diagnosing CDI (high strength of evidence [SOE]). (See Table 1.)

Prevention of CDI: Strategies such as antibiotic stewardship and handwashing campaigns may help prevent CDI (low SOE). Further evidence is needed to confirm that prevention strategies impact patient outcomes such as CDI incidence. (See Table 2.)

Treatment of CDI: Vancomycin is more effective than metronidazole for the initial treatment of CDI (high SOE), while fidaxomicin is more effective than vancomycin for the prevention of recurrent CDI (high SOE). Physicians may take into consideration disease and patient characteristics, effectiveness, potential adverse effects, patient preferences, and costs when choosing an antibiotic to treat CDI. Lactobacillus probiotics, when used as an adjunct to antibiotic therapy, may prevent the recurrence of CDI (low SOE); additionally, probiotics are generally safe in otherwise healthy patients. There is low SOE that FMT may be effective for treating recurrent and relapsed CDI; however, there is consistent positive evidence for its effectiveness in patients with recurrent and relapsed CDI. (See Tables 3, 4, and 5.)

Keywords 
clostridium difficile diagnostic tests
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