Primecuts – This Week in the Journals

July 26, 2019

By Oliver Stewart, MD

Peer Reviewed

With medicine advancing at such a rapid pace, it is crucial for physicians to keep up with the medical literature.  This can quickly become an overwhelming endeavor given the sheer quantity and breadth of literature released on a daily basis. Primecuts helps you stay current by taking a shallow dive into recently released articles that should be on your radar. Our goal is for you to slow down and take a few small sips from the medical literature firehose.

Effect of Systolic and Diastolic Blood Pressure on Cardiovascular Outcomes [1]

The 2017 guidelines released by the American College of Cardiology both redefined the stages of hypertension and outlined more stringent targets [2]. According to the guidelines, high-risk patients have a blood pressure goal of <130/80, while a subset of patients have a BP target of <140/90. Although it is known that elevated systolic BP is associated with adverse cardiovascular outcomes, previous studies have suggested that diastolic BP may follow a J curve, in which both highs and lows are associated with increased cardiovascular morbidity [3].

In this retrospective cohort study, researchers investigated the records of 1.3 million adults in Kaiser Permanente’s Northern California healthcare system. They examined outpatient BP measurements over a two-year baseline period and during an eight-year observational period. Researchers controlled for age, sex, race, BMI and coexisting conditions, including coronary artery disease, diabetes mellitus, hypercholesterolemia, and smoking status. The primary endpoint was a composite outcome of myocardial infarction, ischemic stroke, or hemorrhagic stroke.

Both systolic hypertension (>140 mmHg; hazard ratio per unit increase in z score, 1.18; 95% CI 1.17-1.18) and diastolic hypertension (>90 mmHg; hazard ratio per unit increase in z score, 1.06; 95% CI 1.06-1.07) were independently associated with an increased risk of adverse cardiovascular events. Diastolic blood pressure exhibited a J curve, in which the highest and lowest deciles were associated with increased adverse cardiovascular events.

This study demonstrates that diastolic hypertension is independently associated with adverse cardiovascular outcomes, and it should be treated as such. It also alludes to the danger of more stringent BP targets, as low diastolic BP could be of concern as well. Notably, this study controlled for hyperlipidemia, but not the quantitative degree of hyperlipidemia, which is a potential confounder.

Association Between Time to Treatment With Endovascular Reperfusion Therapy and Outcomes in Patients With Acute Ischemic Stroke Treated in Clinical Practice [4]

Most clinicians have heard the expression “time is brain” at some point during their clinical training. Previous research has demonstrated that faster endovascular reperfusion treatment times are associated with improved outcomes for patients who have suffered acute ischemic stroke [5]. This study further specifies the relationship between reperfusion time and clinical outcomes.

Researchers conducted a retrospective cohort study of 6,756 patients who suffered a large-vessel acute ischemic stroke of the anterior circulation and subsequently received endovascular reperfusion therapy. The main exposures examined were onset of symptoms to arterial puncture time and hospital arrival to arterial puncture time.

The relationship between onset to arterial puncture and clinical outcomes was nonlinear, with a steeper slope in the 30 to 270-minute time frame compared to the 271 to 480-minute time frame. In the 30 to 270-minute group, each fewer 15-minute increment was associated with a greater likelihood of ambulating independently at discharge (absolute increased likelihood, 1.72%; 95% CI 0.08%-3.37%), greater likelihood of discharge to home (2.13%; 95% CI 0.81%-3.44%), and more functional independence at discharge (2.19%; 95% CI 0.71%-3.66%).

In the future, follow-up studies would likely benefit from measuring thrombectomy time rather than arterial puncture time, as the former likely better represents the duration of ischemia.

Benefits and Harms of Oral Anticoagulant Therapy in Chronic Kidney Disease [6]

Chronic kidney disease (CKD) is known to be a prothrombotic state, and severe CKD is associated with increased risk of bleeding [7,8]. As a result, the risk-benefit ratio of prescribing vitamin K antagonists (VKAs) versus non-vitamin K oral anticoagulants (NOACs) in this patient population is unclear. This meta-analysis examined the efficacy and safety of oral anticoagulant therapy in patients with CKD.

Researchers reviewed 45 randomized clinical trials with a total of 34,082 participants that evaluated the use of VKAs and NOACs for any indication (including atrial fibrillation, venous thromboembolism, thromboprophylaxis, and prevention of dialysis access thrombosis, and cardiovascular disease other than atrial fibrillation). Outcomes included stroke or systemic embolism in atrial fibrillation, nonhemorrhagic stroke, hemorrhagic stroke, and all-cause or cardiovascular death.

NOACs had a lower risk of systemic embolism or stroke in patients with atrial fibrillation compared to VKAs (risk ratio 0.79; 95% CI 0.66-0.93). NOACs were also associated with reduced risk of major bleeding when compared to VKAs (risk ratio 0.75; 95% CI 0.56-1.01). Only eight of the trials included participants with an eGFR of less than 15mL/min/1.73 m2, and none of those evaluated NOACs for efficacy or safety.

This systemic review suggests that NOACs are more efficacious, with a safer bleeding risk profile than VKAs, in patients with early CKD. However, further studies involving patients with end-stage and dialysis-dependent disease are necessary, as data for this subset is quite limited.

Prevalence, severity, and nature of preventable patient harm across medical care settings: systematic review and meta-analysis [9]

In recent years, there has been increased research on the prevalence of various types of medical errors leading to patient harm. However, in order to enact effective policy change, it is likely more prudent to focus our efforts specifically on preventable patient harm.

In this meta-analysis, researchers evaluated 66 quantitative observational studies with a total pooled sample of more than 300,000 patients receiving care in any medical setting. The primary outcome was the prevalence of preventable patient harm and secondary outcomes were the severity and types of preventable patient harm.

The pooled prevalence of preventable patient harm was 6% (95% CI 5%-7%) whereas the pooled prevalence of non-preventable and preventable harm combined was 12% (95% CI 9%- 14%). Incidents related to drug management (25%; 95% CI 16%-34%) and other therapeutic management incidents (24%; CI 21%-30%) represented the highest proportions.

One unavoidable limitation of this study is that incidents of preventable patient harm are underreported, and so true prevalence will likely never be known. However, by providing more specific data regarding the type and nature of preventable patient harm, institutional interventions can be better targeted.


Short-course primaquine for the radical cure of Plasmodium vivax malaria: a multicentre, randomised, placebo-controlled non-inferiority trial [10]

Primaquine is the most widely used treatment of Plasmodium vivax malaria, but adherence to the standard, 14-day regimen has been an issue. This multicenter, randomized, placebo-controlled study of more than 2,000 patients in Afghanistan, Ethiopia, Indonesia, and Vietnam found that a 7-day regimen was non-inferior to the 14-day regimen (difference of 0.02 recurrences per person-year, 95% CI -0.02 to 0.05, p=0.3405).

Incident Atrial Fibrillation in Patients Undergoing Bariatric Surgery: A Systematic Review and Meta‐analysis [11]

Obesity is thought to contribute to atrial fibrillation, and this meta-analysis evaluated seven cohort studies with 7,681 patients total who underwent bariatric surgery. Researchers found that patients had a 0.42-fold decreased risk of atrial fibrillation following bariatric surgery when compared to controls (pooled odds ratio 0.42; 95% CI 0.22-0.83).

Intensive vs Standard Treatment of Hyperglycemia and Functional Outcome in Patients With Acute Ischemic Stroke [12]

This trial randomized 1,151 patients with hyperglycemia following acute ischemic stroke to tight blood glucose control (target blood glucose of 80-130 mg/dL) or standard blood glucose control (80-179 mg/dL) in the 72 hours following stroke. The primary outcome was the proportion of patients with a favorable outcome based on the 90-day modified Rankin Scale score, a stroke disability scale. Enrollment was stopped due to an interim analysis that indicated no significant difference in outcomes at 90 days.

Use of Antibiotics Without a Prescription in the U.S. Population: A Scoping Review [13]

The use of antibiotics without a prescription can lead to adverse effects and increased antimicrobial resistance. This review examined 31 articles that reported on nonprescription use of antibiotics and found that prevalence ranged from 1% to 66%, depending on the population. Several studies found particularly high prevalence among Hispanic/Latino groups.

Dr. Oliver Stewart is a resident physician at NYU Langone Health

Peer reviewed by Christian Torres, MD, chief resident, internal medicine, NYU School of Medicine

Image courtesy of Wikimedia Commons


[1] Flint, A. C., Conell, C., Ren, X, et al. Effect of systolic and diastolic blood pressure on cardiovascular outcomes. NEJM. (2019);381(3):243-251.

[2] 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol 2018;71:e127-e248.

[3] Bhatt DL. Troponin and the J-curve of diastolic blood pressure: when lower is not better. J Am Coll Cardiol, (2016);68:1723-6.

[4] Jahan R, Saver JL, Schwamm LH, et al. Association between time to treatment with endovascular reperfusion therapy and outcomes in patients with acute ischemic stroke treated in clinical practice. JAMA. (2019);322(3):252–263.

[5] Saver JL, Goyal M, van der Lugt A, et al; HERMES Collaborators. Time to treatment with endovascular thrombectomy and outcomes from ischemic stroke: a meta-analysis. JAMA. (2016);316(12):1279-1288.

[6] Ha JT, Neuen BL, Cheng LP, et al. Benefits and harms of oral anticoagulant Therapy in chronic kidney disease: a systematic review and meta-analysis. Ann Intern Med. [Epub ahead of print 16 July 2019].

[7] Lutz J, Menke J, Sollinger D, Schinzel H, et al. Haemostasis in chronic kidney disease. Nephrol Dial Transplant; (2014) 29:29-40.

[8] Molnar AO, Bota SE, Garg AX, et al. The risk of major hemorrhage with CKD. J Am Soc Nephrol. (2016); 27:2825-32.

[9] Panagioti M, Khan K, Keers N, et al. Prevalence, severity, and nature of preventable patient harm across medical care settings: systematic review and meta-analysis. BMJ. (2019); 366:I4185.

[10] Taylor RW, Thriemer K, von Seidlein L, et al. Short-course primaquine for the radical cure of Plasmodium vivax malaria: a multicentre, randomised, placebo-controlled non-inferiority trial. The Lancet. (2019). Published online July 19, 2019.

[11] Chokesuwattanaskul R, Thongprayoon C, Bathini T, et al. Incident atrial fibrillation in patients undergoing bariatric surgery: a systematic review and meta‐analysis. Intern Med J. Accepted Author Manuscript.

[12] Johnston KC, Bruno A, Pauls Q, et al. Intensive vs Standard Treatment of Hyperglycemia and Functional Outcome in Patients With Acute Ischemic Stroke: The SHINE Randomized Clinical Trial. JAMA. 2019;322(4):326–335.

[13] Grigoryan L, Germanos G, Zoorob R, et al. Use of antibiotics without a prescription in the U.S. population: a scoping review. Ann Intern Med. [Epub ahead of print 23 July 2019].