Here are the last 20 additions to the PBrain (total entries as of now = 3840)


Extensive impact of non-antibiotic drugs on human gut bacteria (3821)
Maier L et al Nature 555:623 03-29-2018

Antibiotics alter the gut microbiome, but researchers have discovered that metformin and other widely used nonantibiotic drugs can do the same (e.g., Nature 2015; 528:262).

To see how widespread this phenomenon might be, investigators screened 1000 drugs against 40 common and diverse gut bacterial strains (i.e., both gram-positive and gram-negative strains, and including potential pathogens such as Clostridium difficile). Surprisingly, 24% of the drugs, including members of all therapeutic classes, inhibited growth of at least one bacterial strain. Chemically diverse members of several therapeutic classes - antipsychotics, other psychoactive drugs, proton-pump inhibitors, antineoplastics, and hormones - were particularly likely to inhibit bacterial division. Bacteria that were resistant to various antibiotics also were resistant to the inhibiting effects of nonantibiotics. Indeed, the investigators found that bacterial mutations that eject antibiotics from bacterial cells also ejected some nonantibiotic drugs.

Comment: This study raises many interesting questions. It indicates that reported links between particular diseases and particular microbiome patterns might be confounded by the nonantibiotic drugs that are taken by people with those diseases. It also suggests that use of certain nonantibiotic drugs might promote antibiotic-resistant gut bacteria. Most provocatively, the power of antipsychotics and other psychoactive drugs to inhibit growth of certain gut bacteria raises the question of whether those bacteria might promote some psychiatric and neurological diseases.


Association between use of sodium-glucose cotransporter 2 inhibitors, glucagon-like peptide 1 agonists, and dipeptidyl peptidase 4 inhibitors with all-cause mortality in patients with type 2 diabetes: A systematic review and meta-analysis (3822)
Zheng SL et al JAMA 319:1580 04-17-2018

Sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 agonists conferred benefit, but dipeptidyl peptidase 4 inhibitors didn't have this effect.

In a meta-analysis of 236 randomized trials (≈176,000 patients; ≥12 weeks' duration), researchers evaluated the survival benefits of three major classes of medications used to treat patients with type 2 diabetes - sodium–glucose cotransporter (SGLT)-2 inhibitors, glucagon-like peptide (GLP)-1 agonists, and dipeptidyl peptidase (DPP)-4 inhibitors. A network analysis was used to compare each class of medications with other classes and with placebo.

Compared with placebo controls, SGLT-2 inhibitors lowered absolute mortality risk significantly by 1.0% (hazard ratio, 0.8); the respective results for GLP-1 agonists were 0.6% and 0.9. SGLT-2 inhibitors and GLP-1 agonists were not significantly different from each other. DPP-4 inhibitors yielded no survival benefit over placebo. SGLT-2 inhibitors and GLP-1 agonists yielded a significant survival benefit versus DPP-4 inhibitors. Relative and absolute risk reductions for cardiovascular-related mortality were similar to the those for all-cause mortality. All three classes of drugs were more likely to cause any hypoglycemia than were placebo controls, but active drugs were not more likely to cause major hypoglycemia.

Comment: The authors note that absolute risk reductions for SGLT-2 inhibitors and GLP-1 agonists are similar in magnitude to those found for blood-pressure lowering or LDL cholesterol lowering in patients with type 2 diabetes, but several caveats must be considered. First, most participants in the major trials were at very high risk, with previously known CV disease (e.g., LEADER [NEJM JW Gen Med Jul 15 2016 and N Engl J Med 2016; 375:311], EMPA-REG [NEJM JW Gen Med Oct 15 2015 and N Engl J Med 2015; 373:2117]); these outcomes probably wouldn't apply to lower-risk patients. Second, follow-up times varied among the 236 trials, so the timing of the one percentage-point mortality-reduction is unclear (the large trials ran for 2 to 4 years). And third, retail prices for these drugs can run from US$5000 to $10,000 annually; thus, with numbers needed to treat in the range of 100 to prevent 1 to 2 events over several years, and annual drug costs per event prevented annually can approach or exceed $1 million. - Thomas L. Schwenk, MD and Allan S. Brett, MD


Cardiovascular safety of varenicline, bupropion, and nicotine patch in smokers: A randomized clinical trial (3823)
Benowitz NL et al JAMA Intern Med 2018 Apr 9 04-09-2018

A large randomized trial showed no excess risk for serious adverse CV or peripheral vascular events with varenicline, bupropion, or nicotine patches.

Nicotine replacement therapy (NRT) is not associated with excess risk for adverse cardiovascular (CV) events. However, continuing concerns about CV risk with bupropion and varenicline prompted the FDA and its European counterpart to request that a multinational, industry-funded trial (conducted to evaluate the neuropsychiatric safety of these drugs) be extended to collect additional CV safety data. More than 8000 smokers (mean age, 47) who wanted to quit were randomized to varenicline (1 mg twice daily), bupropion (150 mg twice daily), a tapering NRT regimen (starting with one 21-mg patch once daily), or appropriate placebo controls for 12 weeks, plus 12 weeks of follow-up; a subset of 4500 participants were followed for an additional 28 weeks in the extension study.

At 52 weeks, no differences were observed among treatment and control groups in incidence of major adverse CV events (i.e., CV-related death, nonfatal myocardial infarction, or nonfatal stroke), nor did groups differ in new-onset or worsening peripheral vascular disease, unstable angina, or coronary revascularization.

Comment: Participants with acute or unstable CV disease were excluded from the trial, so these results cannot be applied to that population. In fact, the study population was relatively young and low-risk for CV disease, so these favorable results do not necessarily apply to higher-risk populations. But, for most typical smokers who have various CV risks, these data reassure us that smoking-cessation pharmacotherapies confer no excess CV risk.


Cardiovascular and neuropsychiatric events after varenicline use for smoking cessation (3824)
Gershon AS et al Am J Respir Crit Care Med 197:913 04-01-2018

In a Canadian risk-interval study, varenicline use was associated with substantially elevated risk for adverse CV, but not neuropsychiatric, events.

Varenicline is an effective aid in smoking cessation, but some randomized trials and meta-analyses have suggested that the drug poses substantial cardiovascular (CV) and neuropsychiatric risks. Canadian researchers used healthcare databases to identify all patients in Ontario who began using varenicline between 2011 and 2014 and who had emergency department visits or hospitalizations arising from specified adverse CV or neuropsychiatric events within 1 year before or 1 year after starting varenicline. They then compared the incidence of adverse CV or neuropsychiatric events during the 12-week period after starting varenicline (risk interval) with incidence during the remainder of the 2-year span before and after starting the drug (control interval). Each patient thus served as his or her own control.

Among 4185 patients with CV events, incidence was 34% higher during the risk interval than during the control interval - a significant difference that persisted in various sensitivity analyses. Among 4720 patients with neuropsychiatric events, incidence was 6% higher during the risk interval than during the control interval - a marginally significant difference that was not robust to sensitivity analyses.

Comment: This study reinforces concerns about the CV safety of varenicline, although the absolute risks are small. The authors estimated that 4 adverse CV events per 1000 varenicline users were attributable to varenicline during the risk interval. Note that these results differ from those of another recent study that suggested the CV safety of varenicline; that study was randomized but much smaller (only 2000 varenicline recipients), and its participants likely had lower baseline CV risk (NEJM JW Gen Med Jun 1 2018 and JAMA Intern Med 2018 Apr 9; [e-pub]). Thus, clinicians and patients still should weigh possible CV risks against the drug's clear benefits in aiding smoking cessation - especially for patients with CV risk factors.


Cardiovascular disease and risk management: Review of the American Diabetes Association Standards of Medical Care in Diabetes 2018 (3825)
Chamberlain JJ et al Ann Intern Med 2018 Apr 3 04-03-2018

Background - The ADA offers annual graded recommendations on diabetes management, with evidence quality-graded ratings (A=large randomized clinical trials or meta-analyses; B=cohort studies; C=uncontrolled observational studies; E=expert consensus). This review is a synopsis of the ADA's recommendations for managing cardiovascular disease (CVD) in diabetic patients, which was published in full in the January 2018 issue of Diabetes Care (Diabetes Care 2018; 41(Suppl 1):S86).

Key Recommendations - Recommendations focus on four core areas of diabetic clinical care:


Cessation of ureteral colic does not necessarily mean that a ureteral stone has been expelled (3826)
Hernandez N et al J Urol 199:1011 04-01-2018

We know that a painful ureteral stone has passed if the patient brings it to us. But what about patients whose pain resolves but who don't retrieve their stones? In this single-center retrospective study, researchers identified 52 patients who met the following criteria: acute ureteral colic, stone confirmed by imaging, follow-up within several weeks, and no pain during the 72 hours prior to the follow-up visit.

At the follow-up encounters (which occurred an average of 35 days after the acute presentations), 26% of these pain-free patients still had ureteral stones (seen on plain film, ultrasound, computed tomography, or ureteroscopy). Most of these patients did not have microscopic hematuria. Imaging confirmed passage of stones in the remaining 74% of patients.

Comment: In this study of patients whose acute ureteral colic resolved but who didn't retrieve their stones, the ureteral stone persisted in about one quarter of patients at 1 month. The authors argue for repeat imaging in such patients, so that those with ongoing obstruction and hydronephrosis can be identified and treated. Among patients who don't pass their stones, it's unclear why pain resolves in some but persists in others.


Association of inhaled corticosteroids and long-acting muscarinic antagonists with asthma control in patients with uncontrolled, persistent asthma: A systematic review and meta-analysis (3827)
Sobieraj DM et al JAMA 319:1473 04-10-2018

The 2018 Global Initiative for Asthma update, used in Europe, recommends two new treatment options for uncontrolled asthma that are not included in the National Asthma Education and Prevention Program (NAEPP) guideline that is used currently in the U.S. Now, in two meta-analyses, researchers have examined the evidence to support these new options.

In one meta-analysis, researchers evaluated 15 randomized trials (7122 patients; age, ≥12 years) in which tiotropium (a long-acting muscarinic antagonist [LAMA]) was added to inhaled corticosteroid (ICS) monotherapy or to ICS-plus-long-acting β-agonist (LABA) dual therapy, with the primary endpoint of asthma exacerbations that required oral corticosteroids. Patients treated with ICS plus tiotropium experienced fewer exacerbations (relative risk, 0.67) compared with ICS-plus-placebo recipients. Patients treated with ICS/LABA plus tiotropium (i.e., triple therapy) did not experience fewer exacerbations than did ICS/LABA patients, but asthma worsening (as defined by morning peak flow or day-to-day symptoms) was less likely.

In another meta-analysis, researchers evaluated single maintenance and reliever therapy ("SMART"), with budesonide (an ICS) and formoterol (a LABA) used for both daily control and as a rescue medication in place of albuterol. SMART was compared with standard therapy in 16 trials (22,748 patients, most older than 12). Compared with the same dose of an ICS/LABA combination used twice daily plus as-needed albuterol, SMART led to significantly fewer exacerbations (relative risk, 0.68) but didn't improve day-to-day symptoms.

Comment: Tiotropium currently is FDA approved for adults and children (age, ≥6 years). No FDA indication exists for SMART, and the dry-powder inhaler used for this purpose in Europe is not available in the U.S. The next NAEPP guidelines likely will include tiotropium as add-on therapy, but whether SMART is addressed remains to be seen. I currently treat patients in a stepwise manner: ICS, ICS/LABA, and ICS/LABA/LAMA, and then I consider biologic therapy for allergic or eosinophilic patients. I occasionally use SMART with ICS/formoterol metered-dose inhalers, but I would be more comfortable if we had the European device and an FDA or NAEPP endorsement. - David J. Amrol, MD

Sobieraj DM et al. Association of inhaled corticosteroids and long-acting β-agonists as controller and quick relief therapy with exacerbations and symptom control in persistent asthma: A systematic review and meta-analysis. JAMA 2018 Apr 10; 319:1485.

Krishnan JA and Au DH Time to converge FDA decisions and evidence syntheses for long-acting muscarinic antagonists and SMART in guidelines for the treatment of asthma. JAMA 2018 Apr 10; 319:1441


Disability Parking Forms (3828)
Kney None 05-20-2018

Massachusetts form for disability parking placard

Rhode Island form for disability parking placard


Essential Tremor (3829)
Haubenburger et al NEJM 378:1802 05-10-2018

Essential Tremor clinical practice article from NEJM.

Link to article with video from NEJM.


Diagnosis and Management of the Antiphospholipid Syndrome (3830)
Garcia et al NEJM 378:2010 05-25-2018

Full article


Acute Generalized Exanthematous Pustulosis (3831)
Tokkachjov et al JFP 67:309 05-01-2018

Think of this when a patient has a diffuse rash with some pustules - usually due to a drug.

Full article


On-Demand versus Maintenance Inhaled Treatment in Mild Asthma (3832)
Lasarus NEJM 378:1940 05-19-2018

On-demand Symbicort (formoterol-budesonide) for mild persistent asthma prevents loss of lung function and reduces exacerbations as well as maintenance therapy, at lower cost and with lower ICS doses. Those using on-demand used about 25% the total dose of those who used maintenance Symbicort. The quality of life score with maintenance therapy was higher, but minimally so (ACQ-5 score was 0.11 units higher in the SYGMA2 study - max points on ACQ-5 is 6).

SYGMA1 Trial

SYGMA2 Trial

SYGMA Editorial


Top 20 Research Studies of 2017 for Primary Care Physicians (3833)
Ebell et al AFP 97:581 05-01-2018

Full article


Management of Bleeding in Patients Taking Oral Anticoagulants (3834)
Anderson et al JAMA 319:2032 05-15-2018

For patients treated with an oral anticoagulant (OAC) who experience either life-threatening bleeding or major bleeding at a critical site, management should include at least temporarily discontinuing the OAC, local therapy, supportive measures, and, when appropriate, administering a reversal agent.

Laboratory testing may be useful to determine reversal strategy for life-threatening bleeding or bleeding at a critical site or prior to urgent unplanned procedures.

For dabigatran

For apixaban, edoxaban, and rivaroxaban

Full article


Serum α1-Antitrypsin Concentration in the Diagnosis of α1-Antitrypsin Deficiency (3835)
Hurley et al JAMA 319:2034 05-15-2018

Very nice table showing different mutations and what they mean.

Full article


Dry Eye (3836)
Clayton NEJM 378:2212 06-07-2018

Full article


Rivaroxaban for stroke prevention after embolic stroke of undetermined source (3837)
Hart RG et al NEJM 05-16-2018

Embolic stroke of unknown source (ESUS) is diagnosed when the cause is unclear after diagnostic work-up. Because anticoagulants are effective for prevention of stroke related to cardiac emboli, researchers tested their efficacy for ESUS. They randomized 7213 patients (mean age, 67; 62% men) to treatment with either the factor Xa inhibitor rivaroxaban (15 mg daily) or aspirin (100 mg daily). Patients with >50% stenosis of a major vessel supplying the stroke territory were excluded, as were patients with lacunar infarcts, atrial fibrillation, mechanical valves, and left ventricular thrombi. At least 20 hours of cardiac monitoring was required to exclude intermittent atrial fibrillation. The primary outcome was stroke (ischemic or hemorrhagic) or systemic embolism. The primary safety outcome was major bleeding. Both drugs' manufacturers cosponsored the study.

After a median follow-up of 11 months, the trial was stopped early. The primary outcome did not differ significantly between rivaroxaban and aspirin (annualized rate, 5.1% with rivaroxaban vs. 4.8% with aspirin; P=0.52). Of the outcome events, 95% were ischemic strokes, 5% were hemorrhagic strokes, and only 1% were systemic emboli. Major bleeding was significantly more common with rivaroxaban than with aspirin (annualized rates, 1.8% vs. 0.7%; hazard ratio, 2.7). Symptomatic intracranial hemorrhage was also significantly more common with rivaroxaban (hazard ratio, 4.02).

Comment: This trial showed a neutral result between rivaroxaban and aspirin with regard to stroke prevention, along with an increased risk for serious bleeding with rivaroxaban. This finding suggests that the composition of the clot leading to recurrent events was not amenable to anticoagulation, as it is with other sources such as atrial fibrillation. Patients with ESUS are heterogeneous and include some with mild carotid or vertebral artery atherosclerosis, others with aortic atherosclerosis, and a fraction with patent foramen ovale. Testing a factor Xa inhibitor in a more focused group of patients could be worthwhile, but in the broad category of ESUS, the quest continues for a more effective therapy beyond aspirin alone.


Screening for prostate cancer: US Preventive Services Task Force recommendation statement (3838)
USPSTF JAMA 319:1914 05-08-2018

Background: The USPSTF has updated its 2012 Grade D recommendation against prostate-specific antigen (PSA) screening for prostate cancer (NEJM JW Gen Med Jul 1 2012 and Ann Intern Med 2012; 157:120). This publication is the final version of the draft statement, released in 2017, that received substantial publicity (NEJM JW Gen Med May 15 2017). Public comment and research that has been published since the draft release did not result in any changes.

Key Recommendations:

Comment: This shift from a negative to a relatively neutral position on PSA screening in middle-aged men reflects an interpretation that benefits and harms of screening now are balanced more evenly. This view was influenced by more-positive 13-year follow-up data from the European Randomized Study of Screening for Prostate Cancer (ERSPC; NEJM JW Gen Med Sep 15 2014 and Lancet 2014; 384:2027) and by an increasing trend toward active surveillance rather than aggressive treatment in men with low-grade cancers (generally defined as a Gleason score ≤6). Editorialists predict that PSA screening rates will rise, based on a shared decision-making approach, reversing a substantial decline after the USPSTF's 2012 negative recommendation. However, despite the statistically positive result of the European trial, all-cause mortality was not different between screened and control groups, and only slightly more than 1 prostate cancer death per 1000 men screened was prevented during 13 years of follow-up. The absolute benefit still is very small, and false-positive screenings are common, leading to excess biopsies, overdiagnosis, and complications from overtreatment. - Thomas L. Schwenk, MD


Prophylactic effect of trimethoprim-sulfamethoxazole for pneumocystis pneumonia in patients with rheumatic diseases exposed to prolonged high-dose glucocorticoids (3839)
Park JW et al Ann Rheum Dis 77:644 05-01-2018

Pneumocystis pneumonia (PCP) prophylaxis is effective in HIV-positive patients and other immunosuppressed groups, but consensus is lacking on PCP prophylaxis in patients with rheumatic diseases. In this study, researchers identified 1092 Korean patients with rheumatic diseases who were treated with high-dose steroids (prednisone equivalent, ≥30 mg daily) for longer than 4 weeks. Patients were divided into PCP prophylaxis and control groups based on whether they also received prophylactic trimethoprim-sulfamethoxazole (TMP-SMX), and propensity-score matching created two groups of 235 patients each.

During 1464 person-years, 30 PCP cases occurred, with 37% mortality; only 1 (nonfatal) PCP case occurred among prophylaxis patients. TMP-SMX lowered 1-year PCP incidence and related mortality significantly (adjusted hazard ratios, 0.07 and 0.08, respectively) in the matched population. Only two serious prophylaxis-related adverse events occurred (including 1 case of Stevens-Johnson syndrome). Absent other risk factors for PCP, discontinuing prophylaxis appeared to be safe when steroid doses were <15 mg daily.

Comment: These results should influence practice. Prophylaxis was safe and effective and, in the entire study population, was used more often in patients with risk factors for PCP beyond high-dose steroids (e.g., lymphopenia, higher past steroid use, concomitant cyclophosphamide use). Editorialists recommend prophylaxis, noting "there is little reason to take a risk with a month or more of high-dose glucocorticoids." - Jonathan S. Coblyn, MD


ESC Guidelines for the diagnosis and management of syncope (3840)
Brignole M et al Eur Heart J 03-19-2018

Background: Syncope is a transient loss of consciousness due to cerebral hypoperfusion, with rapid onset, short duration, and complete spontaneous recovery; lifetime risk for syncope is 50% in the general population. A multidisciplinary task force, including experts in cardiology, emergency medicine, geriatrics, internal medicine, neurology, and nursing, updated the 2009 ESC syncope guidelines (Eur Heart J 2009; 30:2631) with evidence-based recommendations.

Key Recommendations:

  1. Initial Diagnostic Evaluation
  2. Subsequent Diagnostic Investigation
  3. Treatment

Comment: These updated European guidelines complement the 2017 American College of Cardiology guidelines (NEJM JW Emerg Med May 2017 and Circulation 2017; 139:25). Practical explanations of each testing modality are detailed, and rational, evidence-based recommendations are provided. Additional resources are available on the ESC guidelines web page. - Daniel D. Dressler, MD, MSc, SFHM, FACP


Here are the last 10 additions to the PBrain by date


Dry Eye (3836)
Clayton NEJM 378:2212 06-07-2018

Full article


Diagnosis and Management of the Antiphospholipid Syndrome (3830)
Garcia et al NEJM 378:2010 05-25-2018

Full article


Disability Parking Forms (3828)
Kney None 05-20-2018

Massachusetts form for disability parking placard

Rhode Island form for disability parking placard


On-Demand versus Maintenance Inhaled Treatment in Mild Asthma (3832)
Lasarus NEJM 378:1940 05-19-2018

On-demand Symbicort (formoterol-budesonide) for mild persistent asthma prevents loss of lung function and reduces exacerbations as well as maintenance therapy, at lower cost and with lower ICS doses. Those using on-demand used about 25% the total dose of those who used maintenance Symbicort. The quality of life score with maintenance therapy was higher, but minimally so (ACQ-5 score was 0.11 units higher in the SYGMA2 study - max points on ACQ-5 is 6).

SYGMA1 Trial

SYGMA2 Trial

SYGMA Editorial


Rivaroxaban for stroke prevention after embolic stroke of undetermined source (3837)
Hart RG et al NEJM 05-16-2018

Embolic stroke of unknown source (ESUS) is diagnosed when the cause is unclear after diagnostic work-up. Because anticoagulants are effective for prevention of stroke related to cardiac emboli, researchers tested their efficacy for ESUS. They randomized 7213 patients (mean age, 67; 62% men) to treatment with either the factor Xa inhibitor rivaroxaban (15 mg daily) or aspirin (100 mg daily). Patients with >50% stenosis of a major vessel supplying the stroke territory were excluded, as were patients with lacunar infarcts, atrial fibrillation, mechanical valves, and left ventricular thrombi. At least 20 hours of cardiac monitoring was required to exclude intermittent atrial fibrillation. The primary outcome was stroke (ischemic or hemorrhagic) or systemic embolism. The primary safety outcome was major bleeding. Both drugs' manufacturers cosponsored the study.

After a median follow-up of 11 months, the trial was stopped early. The primary outcome did not differ significantly between rivaroxaban and aspirin (annualized rate, 5.1% with rivaroxaban vs. 4.8% with aspirin; P=0.52). Of the outcome events, 95% were ischemic strokes, 5% were hemorrhagic strokes, and only 1% were systemic emboli. Major bleeding was significantly more common with rivaroxaban than with aspirin (annualized rates, 1.8% vs. 0.7%; hazard ratio, 2.7). Symptomatic intracranial hemorrhage was also significantly more common with rivaroxaban (hazard ratio, 4.02).

Comment: This trial showed a neutral result between rivaroxaban and aspirin with regard to stroke prevention, along with an increased risk for serious bleeding with rivaroxaban. This finding suggests that the composition of the clot leading to recurrent events was not amenable to anticoagulation, as it is with other sources such as atrial fibrillation. Patients with ESUS are heterogeneous and include some with mild carotid or vertebral artery atherosclerosis, others with aortic atherosclerosis, and a fraction with patent foramen ovale. Testing a factor Xa inhibitor in a more focused group of patients could be worthwhile, but in the broad category of ESUS, the quest continues for a more effective therapy beyond aspirin alone.


Management of Bleeding in Patients Taking Oral Anticoagulants (3834)
Anderson et al JAMA 319:2032 05-15-2018

For patients treated with an oral anticoagulant (OAC) who experience either life-threatening bleeding or major bleeding at a critical site, management should include at least temporarily discontinuing the OAC, local therapy, supportive measures, and, when appropriate, administering a reversal agent.

Laboratory testing may be useful to determine reversal strategy for life-threatening bleeding or bleeding at a critical site or prior to urgent unplanned procedures.

For dabigatran

For apixaban, edoxaban, and rivaroxaban

Full article


Serum &#945;1-Antitrypsin Concentration in the Diagnosis of &#945;1-Antitrypsin Deficiency (3835)
Hurley et al JAMA 319:2034 05-15-2018

Very nice table showing different mutations and what they mean.

Full article


Essential Tremor (3829)
Haubenburger et al NEJM 378:1802 05-10-2018

Essential Tremor clinical practice article from NEJM.

Link to article with video from NEJM.


Screening for prostate cancer: US Preventive Services Task Force recommendation statement (3838)
USPSTF JAMA 319:1914 05-08-2018

Background: The USPSTF has updated its 2012 Grade D recommendation against prostate-specific antigen (PSA) screening for prostate cancer (NEJM JW Gen Med Jul 1 2012 and Ann Intern Med 2012; 157:120). This publication is the final version of the draft statement, released in 2017, that received substantial publicity (NEJM JW Gen Med May 15 2017). Public comment and research that has been published since the draft release did not result in any changes.

Key Recommendations:

Comment: This shift from a negative to a relatively neutral position on PSA screening in middle-aged men reflects an interpretation that benefits and harms of screening now are balanced more evenly. This view was influenced by more-positive 13-year follow-up data from the European Randomized Study of Screening for Prostate Cancer (ERSPC; NEJM JW Gen Med Sep 15 2014 and Lancet 2014; 384:2027) and by an increasing trend toward active surveillance rather than aggressive treatment in men with low-grade cancers (generally defined as a Gleason score ≤6). Editorialists predict that PSA screening rates will rise, based on a shared decision-making approach, reversing a substantial decline after the USPSTF's 2012 negative recommendation. However, despite the statistically positive result of the European trial, all-cause mortality was not different between screened and control groups, and only slightly more than 1 prostate cancer death per 1000 men screened was prevented during 13 years of follow-up. The absolute benefit still is very small, and false-positive screenings are common, leading to excess biopsies, overdiagnosis, and complications from overtreatment. - Thomas L. Schwenk, MD


Chronic Hepatitis B Infection: A Review (3814)
Tang et al JAMA 319:1802 05-01-2018

Full article