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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.

Association of Pharmacological Treatments With Long-term Pain Control in Patients With Knee Osteoarthritis: A Systematic Review and Meta-analysis

Author/s: 
Gregori, D., Giacovelli, G., Minto, C., Barbetta, B., Gualtieri, F., Azzolina, D., Vaghi, P.

IMPORTANCE:

Even though osteoarthritis is a chronic and progressive disease, pharmacological agents are mainly studied over short-term periods, resulting in unclear recommendations for long-term disease management.

OBJECTIVE:

To search, review, and analyze long-term (≥12 months) outcomes (symptoms, joint structure) from randomized clinical trials (RCTs) of medications for knee osteoarthritis.

DATA SOURCES AND STUDY SELECTION:

The databases of MEDLINE, Scopus, EMBASE, Web of Science, and the Cochrane Central Register of Controlled Trials were searched until June 30, 2018 (MEDLINE alerts through August 31, 2018) for RCTs of patients with knee osteoarthritis that had treatment and follow-up lasting 1 year or longer.

DATA EXTRACTION AND SYNTHESIS:

Data at baseline and at the longest available treatment and follow-up of 12 months' duration or longer (or the change from baseline) were extracted. A Bayesian random-effects network meta-analysis was performed.

MAIN OUTCOMES AND MEASURES:

The primary outcome was the mean change from baseline in knee pain. Secondary outcomes were physical function and joint structure (the latter was measured radiologically as joint space narrowing). Standardized mean differences (SMDs) and mean differences with 95% credibility intervals (95% CrIs) were calculated. Findings were interpreted as associations when the 95% CrIs excluded the null value.

RESULTS:

Forty-seven RCTs (22 037 patients; mean age range, mostly 55-70 years; and a higher mean proportion of women than men, around 70%) included the following medication categories: analgesics; antioxidants; bone-acting agents such as bisphosphonates and strontium ranelate; nonsteroidal anti-inflammatory drugs; intra-articular injection medications such as hyaluronic acid and corticosteroids; symptomatic slow-acting drugs in osteoarthritis such as glucosamine and chondroitin sulfate; and putative disease-modifying agents such as cindunistat and sprifermin. Thirty-one interventions were studied for pain, 13 for physical function, and 16 for joint structure. Trial duration ranged from 1 to 4 years. Associations with decreases in pain were found for the nonsteroidal anti-inflammatory drug celecoxib (SMD, -0.18 [95% CrI, -0.35 to -0.01]) and the symptomatic slow-acting drug in osteoarthritis glucosamine sulfate (SMD, -0.29 [95% CrI, -0.49 to -0.09]), but there was large uncertainty for all estimates vs placebo. The association with pain improvement remained significant only for glucosamine sulfate when data were analyzed using the mean difference on a scale from 0 to 100 and when trials at high risk of bias were excluded. Associations with improvement in joint space narrowing were found for glucosamine sulfate (SMD, -0.42 [95% CrI, -0.65 to -0.19]), chondroitin sulfate (SMD, -0.20 [95% CrI, -0.31 to -0.07]), and strontium ranelate (SMD, -0.20 [95% CrI, -0.36 to -0.05]).

CONCLUSIONS AND RELEVANCE:

In this systematic review and network meta-analysis of studies of patients with knee osteoarthritis and at least 12 months of follow-up, there was uncertainty around the estimates of effect size for change in pain for all comparisons with placebo. Larger RCTs are needed to resolve the uncertainty around efficacy of medications for knee osteoarthritis.

Long-Term Drug Therapy and Drug Holidays for Osteoporosis Fracture Prevention: A Systematic Review

Author/s: 
Fink, Howard A., MacDonald, Roderick, Forte, Mary L., Rosebush, Christina E., Ensrud, Kristine E., Schousboe, John T., Nelson, Victoria A., Ullman, Kristen, Butler, M., Olson, Carin M., Taylor, Brent C., Brasure, Michelle, Wilt, Timothy J.

BACKGROUND:

Optimal long-term osteoporosis drug treatment (ODT) is uncertain.

PURPOSE:

To summarize the effects of long-term ODT and ODT discontinuation and holidays.

DATA SOURCES:

Electronic bibliographic databases (January 1995 to October 2018) and systematic review bibliographies.

STUDY SELECTION:

48 studies that enrolled men or postmenopausal women aged 50 years or older who were being investigated or treated for fracture prevention, compared long-term ODT (>3 years) versus control or ODT continuation versus discontinuation, reported incident fractures (for trials) or harms (for trials and observational studies), and had low or medium risk of bias (ROB).

DATA EXTRACTION:

Two reviewers independently rated ROB and strength of evidence (SOE). One extracted data; another verified accuracy.

DATA SYNTHESIS:

Thirty-five trials (9 unique studies) and 13 observational studies (11 unique studies) had low or medium ROB. In women with osteoporosis, 4 years of alendronate reduced clinical fractures (hazard ratio [HR], 0.64 [95% CI, 0.50 to 0.82]) and radiographic vertebral fractures (both moderate SOE), whereas 4 years of raloxifene reduced vertebral but not nonvertebral fractures. In women with osteopenia or osteoporosis, 6 years of zoledronic acid reduced clinical fractures (HR, 0.73 [CI, 0.60 to 0.90]), including nonvertebral fractures (high SOE) and clinical vertebral fractures (moderate SOE). Long-term bisphosphonates increased risk for 2 rare harms: atypical femoral fractures (low SOE) and osteonecrosis of the jaw (mostly low SOE). In women with unspecified osteoporosis status, 5 to 7 years of hormone therapyreduced clinical fractures (high SOE), including hip fractures (moderate SOE), but increased serious harms. After 3 to 5 years of treatment, bisphosphonate continuation versus discontinuation reduced radiographic vertebral fractures (zoledronic acid; low SOE) and clinical vertebral fractures (alendronate; moderate SOE) but not nonvertebral fractures (low SOE).

LIMITATION:

No trials studied men, clinical fracture data were sparse, methods for estimating harms were heterogeneous, and no trials compared sequential treatments or different durations of drug holidays.

CONCLUSION:

Long-term alendronate and zoledronic acid therapies reduce fracture risk in women with osteoporosis. Long-termbisphosphonate treatment may increase risk for rare adverse events, and continuing treatment beyond 3 to 5 years may reduce risk for vertebral fractures. Long-term hormone therapy reduces hip fracture risks but has serious harms.

PRIMARY FUNDING SOURCE:

National Institutes of Health and Agency for Healthcare Research and Quality. (PROSPERO: CRD42018087006).

Keywords 
bias hip fracture postmenopause alendronate fracture osteoporosis Research
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