#111: Hotcakes – Complementary Medicine in Cancer, Dosing Aspirin by Body Weight, Marijuana & Respiratory Symptoms, Penicillin Allergies and More!

August 31, 2018 | By Sarah Phoebe Roberts

Dr. Neda Frayha (@nedafrayha) of Primary Care RAP (Hippo Education) joins us this month for our thoughts and analysis of some recent (and not so recent) journal articles that interested us this month. Our articles spanned topics that include at cancer survival among patients pursuing treatment with complementary medicine, the effect of body weight on effectiveness of preventive aspirin dosing, strategies to promote physician leadership, respiratory symptoms in those with marijuana use and MRSA risk among patients with penicillin allergies. ACP members can claim free CME-MOC at acponline.com/curbsiders (goes live 0900 EST on podcast release date).

Thoughts on the Journal Club series? Article or guest nominations? Compliments or complaints? You can reach us at thecurbsiders@gmail.com. We are also on Facebook, Instagram, and Twitter: @thecurbsiders.

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

Hotcakes:
Johnson SB, Park HS, Gross CP, Yu JB. Complementary Medicine, Refusal of Conventional Cancer Therapy, and Survival Among Patients With Curable Cancers. JAMA Oncol. Published online July 19, 2018. doi:10.1001/jamaoncol.2018.2487

What’s the clinical question? Who is the patient population?
Who are the patients using complementary medicine (CAM) to treat cancer? What is the relationship between use of CM and both adherence to conventional treatment and cancer survival?

Background Info
This article was cited widely in the regular press (NYT, Time, NBC News). Complementary & alternative medicine is a multibillion $ industry; patients may underreport how often they seek these services; other studies have suggested that up to 88% of cancer patients use CM as part of their treatment, ⅔ of patients with cancer believe complementary medicine will prolong their lives, and ⅓ believe it will cure their disease.

Design/Setting/Participants
Retrospective observational cohort study of 1.9 M patients in the National Cancer Database (data from 1500 cancer centers across the U.S.); 258 patients who had used complementary medicine and 1032 were in the non-”complementary medicine” control group (matched by age, race, cancer type, stage, comorbidity score, insurance type). Cancer types included were non-metastatic breast, prostate, lung, and colorectal. Ten year period.

Outcomes?
Use of complementary medicine was associated with higher refusal rates of surgery, chemotherapy, radiation (53% vs 2%!), and hormone therapy. Use of complementary medicine was also associated with poorer 5-year survival rates (82.2% vs 86.6%). But, once adherence measures were included in the analysis, complementary medicine was no longer associated with an increased risk of death.

Bottom line?
Patients who elect to receive complementary medicine to the exclusion of CCT have greater risk of death. Notably, the statistically significant relationship between complementary medicine and survival disappears after controlling for treatment delay/refusal. The authors say the critical take-home point is that healthcare providers should be proactive in discussing complementary medicine with their patients and emphasizing the importance of adherence to conventional therapy. Nobody is saying NOT to do complementary medicine. They’re just saying, be sure to use gold-standard conventional treatment as well.

Rothwell, Peter M et al. Effects of aspirin on risks of vascular events and cancer according to bodyweight and dose: analysis of individual patient data from randomised trials. The Lancet, Volume 392, Issue 10145, 387-399

What’s the clinical question? Who is the patient population?
Low dose aspirin for primary prevention of cardiovascular events has only modest benefit. Is the effectiveness of aspirin dosing related to patient weight, height and body size? Ten previous randomised trials of aspirin for primary prevention of cardiovascular events (>100,000 patients) were examined with patients stratified according to weight.

Strengths?
Individual patient level data was used instead of aggregate data from each trial. Authors validated findings by analyzing trials of aspirin for secondary prevention of stroke and by assessing the relationship between patient weight and effects of aspirin on cancer risk.

Weaknesses?
Trials were from the late 1970s to early 2000s and differences in current medical therapy might affect the results (e.g. use of statins, new diabetes medications). Authors could not control for patient adherence to therapy.

Bottom line?
A “one-dose-fits-all strategy for daily aspirin use is unlikely to be optimal “ (Rothwell et al. Lancet 2018). Low dose aspirin (75-100 mg once daily) is not effective for prevention of cardiovascular events in patients weighing more than 70 kg (~154 lbs). Aspirin doses of ≥300 mg once daily prevented adverse cardiac events in those weighing greater than ≥70 kg. Randomised trials comparing the safety and efficacy of weight based aspirin are warranted. There is no current guidance to suggest aspirin dosing for patients outside 50-69 kg range.

See Also:

• Theken KN and Grosser T. Lancet 2018 https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(18)31307-2/fulltext
• Soloway B. NEJM Journal Watch GIM 2018 (Needs Subscription) https://www.jwatch.org/na47166/2018/07/24/weight-based-aspirin-dosing-primary-cardiovascular
• Medscape article by Steve Stiles August 2, 2018 https://www.medscape.com/viewarticle/900139#vp_1
• Angood, P and Birk, S. The value of physician leadership. PEJ  May/June 2014.

What’s the clinical question? Who is the patient population?
How can physicians practice the clinical and professional leadership necessary to support and expand high-quality health care?

Strengths?
Summarizes comprehensive literature review and qualitative data (physician interviews).

Weaknesses?
Published in 2014 and therefore may not accurately reflect current political and social climate and its impact on the landscape of health care provision.

Bottom line?
Physicians who take on active leadership roles have the potential to positively influence their institutions, the health of their patients, and the health care system more broadly. Physician-run hospitals show (1) Higher Quality-measure scores; (2) Physician leadership engagement associated with lean management, permancement management, and overall management; (3) Reduced rates of hospital acquired infections, readmission rate, patient satisfaction, and… improved financial margins.

See Also:

• Tasi MC. Does physician leadership affect hospital quality, operational efficiency, and financial performance? Health Care Manage Rev. 2017 Jul 11. doi: 10.1097/HMR.0000000000000173.
• Sarto F. Clinical leadership and hospital performance: assessing the evidence base.
• Driving Physician Engagement With Physician Leadership by Peter B. Angood, MD, FRCS(C), FACS, MCCM
• LEAD – Leadership Education And Development. https://www.aamc.org/members/leadership/catalog/364660/leadershipeducationanddevelopmentcertificateprogram.html

Ghasemiesfe et al. Marijuana Use, Respiratory Symptoms, and Pulmonary Function: A Systematic Review and Meta-analysis. Ann Intern Med. 2018;169(2):106-115. DOI: 10.7326/M18-0522

What’s the clinical question? Who is the patient population?
What pulmonary outcomes are associated with marijuana use among adults and adolescents? 

Strengths?
Meta-analysis of 22 observational and interventional studies published between 1973 and 2018. Multiple independent reviewers extracted data and assessed for bias and strength of evidence. 

Weaknesses?
Considerable variability among the studies selected for analysis, e.g. differences in patient characteristics, respiratory outcomes examined, study design, and extent of marijuana exposure. Per authors, “Few studies were at low risk of bias”.

Bottom line?
Some evidence that marijuana use is associated with respiratory outcomes such as wheezing, cough and sputum production. Further research is needed.

Blumenthal Kimberly G, Lu Na, Zhang Yuqing, Li Yu, Walensky Rochelle P, Choi Hyon K et al. Risk of meticillin resistant Staphylococcus aureus and Clostridium difficile in patients with a documented penicillin allergy: population based matched cohort study. BMJ 2018; 361:k2400.

What’s the clinical question? Who is the patient population?
Prospective cohort study of UK adults with and without documented penicillin allergy. Outcomes of interest are MRSA and C Difficile infection and use of non-penicillin antibiotic (abx) alternatives.

Important background info
Penicillin is one of the most commonly documented drug allergies; some estimates have it at 10% of all patients. 95% of reported PCN-allergic patients are actually tolerant of the drug (Sacco et al, Allergy 2017). 80% of patients with immediate hypersensitivity are no longer allergic after 10 years (Blanca et al, J Allergy Clin Immunol 1999). With increasing incidence, M&M, and financial cost of infections like MRSA and C diff, antibiotic stewardship is more important than ever. This study endeavored to assess the relationship between penicillin allergy and development of MRSA or C diff.

Outcomes?
In PCN allergic patients, adjusted hazard ratio for MRSA was 1.69 (CI 1.5-1.9) and C diff 1.25 (1.12-1.4). Adjusted incidence rate ratios for alternative abx use in these patients were 4 for macrolides and clindamycin and 2 for fluoroquinolones.

Bottom line?
Patients with a documented penicillin allergy are at higher risk of MRSA and C Difficile, which may be attributable to the β-lactam alternatives often prescribed to patients with penicillin allergies. Verification of penicillin allergies and practicing antibiotic stewardship may reduce the risk of patients contracting MRSA or C Difficile.

Dr. Frayha: “This will change my practice; I will pay more attention to my penicillin-allergic patients, especially if they are requiring antibiotics from me, and I am finally getting tested myself for a questionable penicillin allergy from when I was a kid!”

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. Understand the statistical relationships between complementary medicine, conventional cancer treatment and survival in patients with non-metastatic cancers.
2. Learn the most recent literature on the efficacy of aspirin as it pertains to vascular events and cancer especially in relation to bodyweight.
3. Learn what a review of the literature shows is the value of physician leadership and how they can positively influence their institutions, the health of their patients and the health care system.
4. Learn evidence for adverse respiratory symptoms in those who use marijuana.
5. Learn the relationship between documented penicillin allergy and risk of MRSA or Clostridium difficile.

Disclosures: Dr Frayha reports no relevant financial disclosures. The Curbsiders report no relevant financial disclosures.

Time stamps:

• 00:00 Disclaimer, intro, guest bio
• 05:05 Do patients using complementary medicine for cancer therapy have worse outcomes?
• 13:11 Does low dose aspirin work for primary prevention of major adverse cardiac events?
• 19:16 Do physicians make better leaders?
• 24:55 Does marijuana cause respiratory symptoms?
• 30:40 Does penicillin allergy confer increased risk for C Diff and MRSA infection?
• 38:40 Wrap-up and outro