Bringing Data to Life: Interactive Visualizations of Complex Data

More Beds or More Chairs? Using a Science-Based Approach to Address the Opioid Epidemic

When Tissue Is No Longer the Issue: Tissue-Agnostic Cancer Therapy Comes of Age

Matching unique features of cancer types with effective therapies is a cornerstone of precision medicine. Clinical success has been seen in inhibiting specific molecular alterations that drive the growth of cancer cells and targeting molecules whose elevated expression is confined to cancer cells. In addition, cancer cells can have vulnerabilities induced by somatic mutations they carry; attacks on these vulnerabilities range from specific molecular alterations pointing to direct drug strategies to harnessing immune recognition of genetically altered epitopes produced by the cancer cells. Recent advances have found that the success of biomarker-driven cancer therapy may be relevant across sites of origin. For example, cancer types that show DNA mismatch repair deficiency, such as colon, biliary, and endometrial cancer, are more sensitive to immune checkpoint inhibition. Several large, ongoing clinical trials with a “basket” design are combining tumor tissue genomics with potential off-the-shelf therapies in drug development, and more tissue-agnostic biomarker therapies are reaching the bedside.

Tumor Necrosis Factor Inhibitors and Cancer Recurrence in Swedish Patients With Rheumatoid Arthritis: A Nationwide Population-Based Cohort Study: Annals of Internal Medicine: Vol 169, No 5

Background: Use of tumor necrosis factor inhibitors (TNFi) in patients with a history of cancer remains a clinical dilemma. Objective: To investigate whether TNFi treatment in rheumatoid arthritis (RA) is associated with increased risk for cancer recurrence. Design: Population-based cohort study based on linkage of nationwide registers. Setting: Sweden. Participants: Patients with RA who started TNFi treatment between 2001 and 2015, after being diagnosed with cancer, and matched patients with RA and a history of the same cancer who had never received biologics. Measurements: The primary outcome was the first recurrence of cancer. Adjusted Cox proportional hazards models were used to estimate hazard ratios (HRs), taking into account time, cancer type, and whether the cancer was invasive or in situ (or tumor, node, metastasis [TNM] classification system stage in a subset of patients). Results: Among 467 patients who started TNFi treatment (mean time after cancer diagnosis, 7.9 years), 42 had cancer recurrences (9.0%; mean follow-up, 5.3 years); among 2164 matched patients with the same cancer history, 155 had recurrences (7.2%; mean follow-up, 4.3 years) (HR, 1.06 [95% CI, 0.73 to 1.54). Hazard ratios were close to 1 in analyses of patient subsets matched on cancer stage or with similar time from index cancer diagnosis to the start of TNFi treatment, as well as in unmatched analyses. Several CIs had upper limits close to 2. Limitation: The outcome algorithm was partly nonvalidated, and channeling bias was possible if patients with a better index cancer prognosis were more likely to receive TNFi. Conclusion: The findings suggest that TNFi treatment is not associated with increased risk for cancer recurrence in patients with RA, although meaningful risk increases could not be ruled out completely. Primary Funding Source: ALF (an agreement in Stockholm County Council concerning medical education and research in health and medical care), the Swedish Cancer Society, the Swedish Foundation for Strategic Research, and the Swedish Research Council.

Effect of Variation in Published Stroke Rates on the Net Clinical Benefit of Anticoagulation for Atrial Fibrillation

Background: Stroke rates in patients with nonvalvular atrial fibrillation (AF) who are not receiving anticoagulant therapy vary widely across published studies; the resulting effect on the net clinical benefit of anticoagulation in AF is unknown. Objective: To determine the effect of variation in published AF stroke rates on the net clinical benefit of anticoagulation. Design: Markov model decision analysis. Warfarin was the base case, and non–vitamin K antagonist oral anticoagulants (NOACs) were modeled in a secondary analysis. Setting: Community-dwelling adults. Patients: 33 434 adults with incident AF. Measurements: Quality-adjusted life-years (QALYs). Results: Of the 33 434 patients, 27 179 had a CHA2DS2-VASc (congestive heart failure, hypertension, age, diabetes, stroke, and vascular disease) score of 2 or more. The population benefit of warfarin anticoagulation for these patients was least using stroke rates from the ATRIA (AnTicoagulation and Risk Factors In Atrial Fibrillation) study and greatest using those from the Danish National Patient Registry (6290 QALYs [95% CI, ±2.3%] vs. 24 110 QALYs [CI, ±1.9%]; P < 0.001). The optimal CHA2DS2-VASc score threshold for anticoagulation was 3 or more using stroke rates from ATRIA, 2 or more using those from the Swedish AF cohort study, 1 or more using those from the SPORTIF (Stroke Prevention using ORal Thrombin Inhibitor in atrial Fibrillation) study, and 0 or more using those from the Danish National Patient Registry. Accounting for lower rates of NOAC-associated intracranial hemorrhage decreased optimal CHA2DS2-VASc score thresholds, but these thresholds still varied widely. Limitation: Measured benefit may not generalize to other populations. Conclusion: Variation in published AF stroke rates for patients not receiving anticoagulant therapy results in multifold variation in the net clinical benefit of anticoagulation. Guidelines should better reflect the uncertainty in current thresholds of stroke risk score for recommending anticoagulation. Primary Funding Source: None.

U.S. Food and Drug Administration Precertification Pilot Program for Digital Health Software: Weighing the Benefits and Risks

In 2017, the U.S. Food and Drug Administration (FDA) announced a new program for software classified as a medical device. The Digital Health Software Precertification (Pre-Cert) Program is designed to expedite regulatory review for companies that demonstrate quality and organizational excellence in software development. Although Pre-Cert is intended to promote the worthy goals of access and innovation in digital health, many questions have been raised. In particular, Pre-Cert may reduce incentives for developers to study the safety and effectiveness of their software products before patients start to rely on them. Although postmarket surveillance can mitigate risks of these products, the FDA does not have as much authority after a product's widespread use to enforce data collection deadlines. Pre-Cert may also create confusion for patients and physicians, who may believe that marketed products were subject to rigorous study.

Device Closure Versus Medical Therapy Alone for Patent Foramen Ovale in Patients With Cryptogenic Stroke: A Systematic Review and Meta-analysis: Annals of Internal Medicine: Vol 168, No 5

This article has been corrected. The original version (PDF) is appended to this article as a Supplement. Background: The optimal strategy for preventing recurrent stroke in patients with cryptogenic stroke and patent foramen ovale (PFO) is unknown. Purpose: To compare transcatheter PFO closure with medical therapy alone for prevention of recurrent stroke in patients with PFO and cryptogenic stroke. Data Sources: PubMed and the Cochrane Library (without language restrictions) from inception to October 2017, reference lists, and abstracts from cardiology meetings. Study Selection: Randomized trials enrolling adults with PFO and cryptogenic stroke that compared stroke outcomes (main outcome) and potential harms in those receiving transcatheter device closure versus medical therapy alone. Data Extraction: Two investigators independently extracted study data and rated risk of bias. Data Synthesis: Of 5 trials, 1 was excluded because it used a device that is no longer available due to high rates of complications and failure. Four high-quality trials enrolling 2531 patients showed that PFO closure decreased the absolute risk for recurrent stroke by 3.3% (risk difference, −0.033 [95% CI, −0.062 to −0.004]) compared with medical therapy. The treatment strategies did not differ in rates of transient ischemic attack or major bleeding. Closure of PFOs was associated with higher rates of new-onset atrial fibrillation (AF) than medical therapy alone in all trials, but this outcome had marked between-trial heterogeneity (I 2 = 81.9%), and high event rates in some groups resulted in extreme values for CIs. Limitation: Heterogeneity of device type and antithrombotic therapy across trials, small numbers for some outcomes, and heterogeneous and inconclusive AF results. Conclusion: In patients with PFO and cryptogenic stroke, transcatheter device closure decreases risk for recurrent stroke compared with medical therapy alone. Because recurrent stroke rates are low even with medical therapy alone and PFO closure might affect AF risk, shared decision making is crucial for this treatment. Primary Funding Source: None.

When Clinical Practice Guidelines Collide: Finding a Way Forward

A Cautionary Tale of Warning Messages on Food Products: The Case of Sugar-Sweetened Beverages

Firearm-Related Injury and Death: A U.S. Health Care Crisis in Need of Health Care Professionals