Primecuts – This Week In The Journals

June 14, 2016

syphillis_or_gonorrhea__-_NARA_-_515076Rina Mauricio, MD

Peer Reviewed 

The presidential primary season ended this week. Former senator Hillary Clinton secured enough delegates to win the Democratic nomination, though her opponent Bernie Sanders has not given up the fight. On the Republican side, Donald Trump is focused on the general election, with Ted Cruz and John Kasich long gone from the race.

This presidential election has already proven to be historic. Hillary Clinton is likely to be the democratic nominee, thus securing her place in history as the first female presidential nominee. And Donald Trump, despite all doubts, has managed to secure the vocal support of those in his party, notably that of Paul Ryan. Should he be the confirmed republican nominee, his bid for president will surely be unforgettable, if not for his politics but for the media hype that will surround his campaign. This upcoming presidential election promises to be lively and historic. With that, we turn to the latest, history-making news in the journals.

USPSTF recommends screening for syphilis in high risk groups every 3 months:

The last recommendations from the US Preventive Services Task Force on syphilis screening in asymptomatic men and nonpregnant women were written in 2004. Given the recent increase in primary and syphilis infection since 2000, new screening guidelines are needed. The USPSTF task force conducted a review of literature from 2004 to 2015 to update syphilis screening guidelines.1

The task force addressed four key questions when establishing their recommendations: effectiveness of screening in reducing syphilis complications and transmission, effectiveness of risk assessment methods, accuracy of diagnostic tests and strategies, and harms related to screening.

The task force identified two thousand potentially relevant articles. However, ultimately, only 9 articles were relevant to the four key questions and subsequently reviewed. Four studies found that routine screening every 3 months in HIV positive men and men who have sex with men (MSM) versus more infrequent screening resulted in a higher detection rate of asymptomatic syphilis. The task force reviewed five studies to determine the accuracy of diagnostic tests, though the authors admit that several of the studies were limited in both method and applicability. Overall, these studies show that initial nontreponemal tests (ie the VDRL or RPR test) should be followed by a confirmatory treponemal antibody detection test (ie the FTA-ABS or TP-PA test). There were no studies identified that answered the effectiveness of risk assessment methods and harms related to screening.

The USPSTF subsequently issued a recommendation to screen for syphilis in asymptomatic, nonpregnant individuals at increased risk for infection. Individuals at increased risk are MSM and HIV positive men and women. The review of the evidence also highlights the overall lack of research on optimal screening methods, risk assessment tools and harms from screening.

New study does not support the use of intensive blood-pressure control in patients with intracerebral hemorrhage:

The ideal blood pressure goal for patients with intracerebral hemorrhage remains controversial. On the one hand, there is a concern for hematoma expansion and subsequent morbidity and mortality in patients with intracerebral hemorrhage and poorly controlled blood pressure. On the other hand, adequate blood pressure is necessary for cerebral perfusion. The investigators of ATACH-2 conducted a trial to determine whether rapid lowering of blood pressure after symptom onset would result in improved morbidity and mortality.2

In an international, multicenter, prospective randomized open-label trial, researchers assigned1000 participants to intensive treatment versus standard treatment. Study investigators defined intensive treatment as hourly systolic blood pressure of 110 to 139 mmHg, versus 140 to 179 mmHg in the standard treatment group. Eligible patients were those 18 years of age or older with a Glasgow coma Scale score of 5 or more and with hematoma measurement of less than 60cm3 on CT scan. Treatment was initiated within 4.5 hours of symptom onset. Intravenous nicardipine was the first medication used, with the dose titrated according to a prespecified protocol. If systolic blood pressure target was not reached, despite maximum nicardipine infusion for 30 minutes, then intravenous labetalol was used. Subsequent medications used were at the discretion of the provider. CT scans were done within 24 hours of treatment initiation and read by individuals blinded to treatment assignments. Investigators defined primary treatment failure as not achieving target systolic blood pressure within 2 hours after randomization. The primary end point was death or moderate to severe disability, as defined by the modified Rankin scale score, at least 10 percentage points lower in the intensive treatment group at 3 month follow-up. An interim analysis showed no difference between the two groups and enrollment was stopped early.

Of the 961 participants with data for analysis of primary outcome, death or disability was observed in 38.7% of patients in the intensive-treatment group versus 37.7% of patients in the standard-treatment group. The percentage of patients with serious treatment-related adverse events was 1.6% in the intensive treatment group and 1.2% in the standard group. Based on these results, the researchers concluded that intensive blood pressure reduction in patients with intracerebral hemorrhage does not provide an incremental benefit.

The ATACH-2 trial results support the previous findings of the INTERACT2 trial, which showed no difference with aggressive versus lenient blood pressure control in patients with intracerebral hemorrhage.  Therefore there is yet to be evidence from randomized trials supporting achieving a goal systolic blood pressure of <140 mmHg within 1-2 hours. Further studies are needed to determine a systolic blood pressure goal in this cohort and whether initiation of treatment sooner than 4.5 hours after symptom onset will have an effect on morbidity and mortality.

Novel score is proposed to determine bleeding risk in patients on anticoagulation with atrial fibrillation:

The HAS-BLED or ORBIT scores are often used in conjunction with the CHADS2-VASC score to determine the risk/benefit of anticoagulation in patients with atrial fibrillation. These bleeding scores, however, have only modest predictive ability. In recent years, researchers have discovered an associated within biomarkers and bleeding risk. A recent study proposes a new biomarker based score, the ABC-bleeding score, to prognosticate risk of major bleeding in these patients.3

Researchers used data from the ARISTOTLE trial for score derivation. The primary goal of the ARISTOTLE trial was to assess efficacy of apixaban versus warfarin in patients with atrial fibrillation and increased stroke risk. Upon enrollment in the ARISTOTLE trial, cardiac troponin-I, troponin-T, GDF-15, cystatin C, NT-proBNP, creatinine, hemoglobin and hematocrit levels were also measured. Major bleeding events were defined as hemoglobin drop of 2g/L or more, transfusion of two or more units of packed red blood cells, fatal bleeding or bleeding in a critical organ. Models were developed using biomarker and clinical data. The strongest predictors of major bleeding were GDF-15, hemoglobin, troponin-T, age and previous bleeding. The concordance index (or c-index), which compares predictive versus actual outcome when using a predictive model, for the ABC-bleeding score was 0.68 (95% CI 0.66-0.70). This is compared to a c-index of 0.61 for the HAS-BLED score (95% CI 0.59-0.63) and 0.65 for the ORBIT score (95% CI 0.62-0.67). These results were then validated externally using data from the RE-LY trial, which compared dabigatran and warfarin in patients with atrial fibrillation and increased stroke risk. The ABC-bleeding score in this cohort resulted in a c-index of 0.71 (95% CI 0.68-0.73).

This study proposes a novel risk assessment tool for bleeding risk while on anticoagulation in patients with atrial fibrillation. Its strength lies in its derivation and validation using data from a cohort in which the score should be used, and it was shown to perform as well as current risk assessment tools. However, the c-index for the ABC score is only incrementally better than the HAS-BLED or ORBIT score. Additionally, the score depends on biomarker levels, some of which (ie GDF-15) are not as readily obtained.

Elsewhere in the journals: 

A higher risk of heart failure was not found in patients on DPP-4 inhibitors:

Multiple, conflicting studies have been published regarding the risk for heart failure hospitalizations in patients on DPP-4 inhibitors. A retrospective study of patients looked at events of hospitalized heart failure in patients on saxagliptin or sitagliptin versus pioglitazone, sulfonylureas and long-acting insulin.4 A higher risk of hospitalized heart failure was not observed in patients taking sitagliptin or saxagliptin. Given the numerous other conflicting studies on this subject, these results will need to be replicated. 

Novel gene is found that correlates with lower non-HDL cholesterol levels:

Researchers in Iceland found a sequence variant that correlated with non-HDL cholesterol levels.5 In a sequence that encodes a subunit of the asiaglycoprotein receptor (ASGPR), a 12-base-pair deletion was associated with lower non-HDL cholesterol levels. ASGPR plays a role in endocytosis of LDL receptors from the cell membrane and therefore postulated that this mutation leads to decreased levels of functional ASGPR, which decreasedremoval of LDL receptors from the cell membrane, leading to lower non-HDL levels.

The prevalence of obesity is on the rise in women:

Researchers determined the prevalence of obesity from 2013-2014 using recent NHANES survey results.6 The prevalence of obesity was 35.0% for men and 40.4% for women during this time period. When comparing this data to prior NHANES survey results from 2005, the prevalence of obesity and class 3 obesity was on the rise for women from 2005-2014, despite adjusting for age, race, education level and smoking status. Further studies are needed to elucidate the cause for this increase.

Dr. Rina Mauricio is a 2nd year resident, Department of Medicine, NYU Langone Medical Center

Peer reviewed by Matthew Dallos, Chief Resident, Medicine,  NYU Langone Medical Center

Image courtesy of Wikimedia Commons 


  1. Force USPST, Bibbins-Domingo K, Grossman DC, et al. Screening for Syphilis Infection in Nonpregnant Adults and Adolescents: US Preventive Services Task Force Recommendation Statement. Jama 2016;315:2321-7.
  2. Qureshi AI, Palesch YY, Barsan WG, et al. Intensive Blood-Pressure Lowering in Patients with Acute Cerebral Hemorrhage. The New England journal of medicine 2016.
  3. Hijazi Z, Oldgren J, Lindback J, et al. The novel biomarker-based ABC (age, biomarkers, clinical history)-bleeding risk score for patients with atrial fibrillation: a derivation and validation study. Lancet 2016.
  4. Toh S, Hampp C, Reichman ME, et al. Risk for Hospitalized Heart Failure Among New Users of Saxagliptin, Sitagliptin, and Other Antihyperglycemic Drugs: A Retrospective Cohort Study. Annals of internal medicine 2016;164:705-14.
  5. Nioi P, Sigurdsson A, Thorleifsson G, et al. Variant ASGR1 Associated with a Reduced Risk of Coronary Artery Disease. The New England journal of medicine 2016;374:2131-41.
  6. Flegal KM, Kruszon-Moran D, Carroll MD, Fryar CD, Ogden CL. Trends in Obesity Among Adults in the United States, 2005 to 2014. Jama 2016;315:2284-91.