#102: Hotcakes: Asthma, Smoking Cessation, PCP Prophylaxis, Procalcitonin

July 2, 2018 | By Chris Chiu

Curbsiders’ Journal Club features rapid summary and critical appraisal of recent articles and news stories in internal medicine by The Curbsiders. This month’s topics include: asthma, maintenance versus as needed inhaler use, procalcitonin, Pneumocystis pneumonia prophylaxis, colon cancer screening, smoking cessation, cannabis and cognitive impairment, LDL cholesterol and mortality, plus some medical podcast recommendations. ACP member can claim free CME-MOC at acponline.com/curbsiders (goes live 0900 EST on podcast release date).

Over the last month, we have developed a list of more than 40 interesting articles and news stories that we have been feeding our own brain holes. From this list we have plucked a select few that we really wanted to highlight and share with you.

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Credits:

• Written by: Christopher J Chiu MD, Sarah Phoebe Roberts MPH
• Producers: Christopher J Chiu MD, Sarah Phoebe Roberts MPH
• Hosts: Christopher J Chiu MD, Stuart Brigham MD, Paul Williams MD, and Matthew Watto MD
  Editor: Matthew Watto MD

Part 1: Hotcakes! Main article reviews

Matt: Bateman et al. As-Needed Budesonide–Formoterol versus Maintenance Budesonide in Mild Asthma NEJM May 2018 (SYGMA 2)

• What’s the clinical question? Who is the patient population?
  • Patients with mild asthma often rely heavily on short acting beta agonists and have poor adherence to inhaled steroid maintenance therapy. Is the combination of an as needed steroid inhaler and beta agonist (with a quick onset of action) noninferior to budesonide maintenance therapy?
• Strengths?
  • Large multicenter, randomized trial that looked at meaningful patient outcomes

• Weaknesses?
  • This trial was industry funded and switched from superiority to noninferiority during enrollment, which is suspicious.
• Bottom line?
  • This is practice changing. Patients with mild asthma already use their inhalers sporadically and now we can say that they probably have it right. There was no clinically significant improvement in quality of life or asthma symptoms with daily use of maintenance budesonide and steroid exposure was higher. There is also a potential cost savings. Key point: Formoterol is a long acting beta agonist (LABA) with a quick onset and long duration of action that lends to as needed use for rescue. Salmeterol is also a LABA, but it’s slow onset precludes its use as a rescue inhaler.
• See also: This video of its sister trial (published in same issue of NEJM)

Paul: Halpern et al. A Pragmatic Trial of E-Cigarettes, Incentives, and Drugs for Smoking Cessaion. NEJM May 2018

• What’s the clinical question? Who is the patient population?
  • How effective is it to offer treatment to everybody?
  • What if you add free pharmacotherapy?
  • How effective would e-cigarettes be if free?
  • How effective are financial incentives?
  • Population: Patients who were employed by one of 54 companies and current smokers. Utilized opt-out consent.
• Strengths?
  • Large, pragmatic, and looked at a number of modalities

• Weaknesses?
  • May have underestimated abstinence
  • Motivated patients do better
• Bottom line? 
  • It may be of benefit to companies to offer financial incentives

Part 2: Hot Takes
“Hot Takes” are brief, nugget-sized summaries of recent articles and news items.

Matt: Park JW, Curtis JR, Moon J, et al. Prophylactic effect of trimethoprim-sulfamethoxazole (TMP-SMX) for pneumocystis pneumonia in patients with rheumatic diseases exposed to prolonged high-dose glucocorticoids. Annals of the Rheumatic Diseases 2018;77:644-649.

• What’s the clinical question? Who is the patient population?
  • Is TMP-SMX prophylaxis for Pneumocystis pneumonia (“PCP”) effective for patients with rheumatic disease on high dose steroids?
• Strengths?
  • Examined the real world incidence, safety and efficacy of PCP prophylaxis in patients with rheumatologic disease.

• Weaknesses?
  • This was a retrospective observational trial with only 30 cases of PCP. It was performed in Korea and may not be generalizable to patients in the US.
• Bottom line?
  • PCP prophylaxis with TMP-SMX should be considered for patients receiving >30 mg/day of prednisone, especially if they have risk factors of advanced age, lymphopenia, vasculitis (MPA, GPA, SLE), dermatomyositis, and are taking cyclophosphamide or more than 60 mg/day of prednisone. Continue PCP prophylaxis until steroid dose is tapered below 15 mg/day, especially if other PCP risk factors are present.
• See also: Editorial by Kevin Winthrop and John Baddley in response to Park et al.

Paul: Scott et al. Association of Cannabis With Cognitive Functioning in Adolescents and Young Adults. JAMA Psychiatry June 2018

• What’s the clinical question? Who is the patient population?
  • What is the association between marijuana (cannabis) use in adolescence and cognitive impairment?
  • Patient population: Adolescents and young adults aged less than 26 with heavy or frequent cannabis use. Included neurocognitive testing

• Strengths?
  • Large meta-analysis
• Weaknesses?
  • Didn’t look at longitudinal studies with longer lengths of abstinence
• Bottom line?
  • Cannabis use is associated with a statistically significant but minor decrease in cognitive function, which is mitigated by abstinence

Chris: American Cancer Society Guideline for Colorectal Cancer Screening and Andrew Wolf et al. Colorectal cancer screening for average-risk adults: 2018 guideline update from the American Cancer Society. CA: A Cancer Journal for Clinicians. May 2018

• What’s the clinical question? Who is the patient population?
  • ACS gives NEW “qualified recommendation” that average risk patients start receiving colorectal screening at age 45. This is a change from previous guidelines that recommended screening only average risk African Americans at age 45. It’s only a “qualified recommendation” because there is less direct evidence since most studies do not include many adults aged 45-49. “Strong recommendation” remains for screening patients over 50 years old.

• Strengths?
  • Press release from ACS states “The new recommended starting age is based on colorectal cancer (CRC) incidence rates, results from microsimulation modeling that demonstrate a favorable benefit-to-burden balance of screening beginning at age 45, and the expectation that screening will perform similarly in adults ages 45 to 49 as it does in adults for whom screening is currently recommended (50 and older).” Apparently recent age-specific prevalence rates of CRC suggest the 45-49 year olds are similar to 50-54 year olds and incidence distortion (31.4 vs 58.4 per 1000) is partially influenced by higher uptake of screening at age 50.
  • The article brings up that “starting CRC screening earlier also may contribute to reducing disparities in population groups with a higher disease burden (including black/African American, Alaska Native, and some American Indian groups).”
• Weaknesses?
  • USPSTF (2016) retains an “A recommendation” to start screening at age 50 as well as similar recommendations by the American College of Physicians (2015), The American College of Gastroenterology (2009), National Comprehensive Cancer Network (2018). However, ACS says in their press release that “Two of three microsimulation models conducted for the 2016 United States Preventive Services Task Force (USPSTF) screening recommendations suggested that starting colonoscopy screening with an interval of 15 years at age 45 vs age 50 provided a slightly more favorable balance between the benefits and burden of screening. However, the USPSTF elected not to recommend the younger starting age in 2016, judging the estimated additional benefit to be “modest,” and also noting that one of the three models did not corroborate the additional benefit and there was a lack of empirical evidence to support the change.”
• Bottom line?
  • Important step in making changes to broadly followed screening procedures, but until we know if insurance companies will compensate colonoscopies, it will be difficult to enact. This may only occur if USPSTF changes its recommendations.

Watto: Huang et al. Procalcitonin-Guided Use of Antibiotics for Lower Respiratory Tract Infection (negative trial) NEJM. May 2018.

• What’s the clinical question? Who is the patient population?
  • Can procalcitonin assays effectively determine the need for antibiotics (abx) in adult patients presenting to the ED with lower respiratory tract infection?
• Strengths?
  • Well designed trial in fourteen hospitals w/1656 patients. Looked at meaningful outcomes: abx exposure and safety (adverse events by withholding abx)

• Weaknesses?
  • Procalcitonin (PCT) level alone was not used to determine need for abx. Clinicians could choose to ignore PCT protocol recommendations
• Bottom line?
  • The combo of PCT assays plus clinical judgement did not differ from clinical judgement alone for the primary outcome “antibiotic days by day 30” (4.2 and 4.3 days respectively) suggesting that educating clinicians on appropriate abx use trumps the PCT assay for ED patients.
• See also: Related blog post by Ryan Radecki.
  

   

Infographic excerpted from the Huang et al. NEJM article: BMC Emerg Med. 2017; 17: 25.
Published online 2017 Aug 29. doi:10.1186/s12873-017-0138-1 Creative Commons License http://creativecommons.org/licenses/by/4.0/

Paul: Navarese et al. Association Between Baseline LDL-C level and Total and Cardiovascular Mortality After LDL-C Lowering. JAMA, April 2018

• What’s the clinical question? Who is the patient population?
  •  
  • Using statin, non-statin, or statin plus another agent
  • Looked at trials of patients on LDL lowering therapy
  • Does magnitude of reduction of total and CV mortality after LDL cholesterol (LDL-C) lowering depend on baseline LDL-C
  • Reported CV and mortality date
• Strengths
  • Large, well done meta-analysis that reinforces what we already know.

• Weaknesses?
  • No subgroup analyses. Used trial level and not patient level data.
• Bottom line?
  • Magnitude of LDL-C lowering correlates with risk reduction i.e. patients with higher baseline LDL-C levels saw more benefit from high intensity therapy than patients with lower baseline LDL-C
  • Risk reduction was not seen if baseline levels of LDL-C were under 100 mg/dL
• See also: 
  • Review of Navarese article by Dr. Karol Watson published on JWatch.
  • April 2018 JAMA Editorial by Navar and Peterson.

Part 3: Chiu’s Bites
A quick bite (or two) to close out the show!

• Common confusion between the Rod of Asclepius, an ancient symbol of healing and medicine vs the Caduceus, traditional symbol of Hermes that features two snakes winding around a winged staff with ancient associations with trade, eloquence, trickery, and negotiation. This instagram picture of remarkable frieze shows Medicine’s battle with Death. It did adorns the Department of Health & Wellness in Fulton County, Georgia.
  

• IMReasoning Podcast Episode titled “Words”. We have plugged Art Nahill and Nic Szecket’s podcast before and it is well worth the listen if you want to learn a little bit about implicit bias and how it can affect medical care. They discuss a recent article by Goddu et al Do Words Matter? Stigmatizing language and the transmission of bias in the medical record. Journal of Internal Medicine May 2018 as well as their own experience with doing Implicit Bias Testing. GeriPal also did an episode on the subject. Consider following Dr. Quinn Capers on Twitter.

Disclosures: Dr Chiu reports no relevant financial disclosures. Sarah Roberts reports no relevant financial disclosures. Dr Watto reports no relevant financial disclosures. Dr Williams reports no relevant financial disclosures. Dr Brigham reports no relevant financial disclosures.

Time Stamps:

• 00:00 Announcements

• 00:20 Disclaimer

• 01:00 Intro to Curbsiders Journal Club

• 03:07 Mild asthma and as needed versus maintenance inhaler use

• 09:50 Smoking cessation, e-cigarettes, and financial incentives

• 17:23 Pneumocystis pneumonia prophylaxis

• 22:18 Cannabis and cognitive impairment

• 26:15 Colorectal cancer screening update by American Cancer Society

• 30:37 Procalcitonin for lower respiratory tract infections in the ED

• 37:29 Cholesterol, baseline LDL-C, mortality and cardiovascular events

• 41:01 Incorrect symbology and some podcast recommendations
• 46:22 Outro

Goal:  Listeners will keep current with the medical literature and news through rapid summary and critical appraisal by The Curbsiders

Learning objectives:
After listening to this episode listeners will…

1. Recall the evidence for using as-needed inhaled steroids in the management of asthma.
2. Evaluate the evidence on e-cigarettes or other incentives for smoking cessation.
3. Learn the newest American Cancer Society guidelines on colorectal cancer screening.
4. Determine need for pneumocystis pneumonia prophylaxis in patients with rheumatologic disease on corticosteroids
5. Consider the effects of cannabis use on cognitive function
6. Recall the association between baseline LDL-C level, intensity of lipid lowering therapy and the effect on mortality and cardiovascular events