Can a Positive Attitude Keep Appendicitis Patients From Going Under the Knife?

Appendicitis patients treated with antibiotics who expressed full faith in the healing power of the therapy ahead of time had a lower risk of undergoing appendectomy and dealing with persistent symptoms, a secondary analysis of the CODA trial found, although an expert questioned how actionable the findings were.

Of more than 400 antibiotic patients in the randomized trial who completed a baseline survey, those who believed the treatment would be completely successful had a 13-percentage point lower risk of appendectomy at 30 days versus those who believed antibiotics would be unsuccessful or were unsure (14% vs 26%, respectively; adjusted risk difference [aRD] -13.49, 95% CI -24.57 to -2.40), reported David Flum, MD, MPH, of the University of Washington in Seattle, and colleagues.

Writing in JAMA Surgery, the group said there was “a marked effect within the first 48 hours,” noting that beliefs may have led to differences in antibiotic adherence.

Fewer patients with complete or intermediate positive beliefs about the likelihood of success with antibiotics had persistent symptoms at 30 days (30% and 29%, respectively) compared to those who thought antibiotics would be unsuccessful or were unsure (47%), though this difference was only significant for the intermediate group (aRD -16.0, 95% CI -30.0 to -1.7).

“The magnitudes of some of these associations were large,” the authors wrote, concluding that “this information might be expected to improve shared decision-making, even as we acknowledge that beliefs may influence outcomes in ways not yet fully understood.”

High decisional regret or dissatisfaction with antibiotic treatment at 30 days, observed in 17% of patients, was not linked to belief in treatment success.

The primary analysis of the CODA (Comparison of Outcomes of Antibiotic Drugs and Appendectomy) trial demonstrated that antibiotics were noninferior to appendectomy, though many antibiotic patients still required appendectomy later, analyses showed. In the current study of antibiotic patients in the CODA trial that had filled out the baseline survey, 20% ultimately required subsequent appendectomy.

“Appendicitis, traditionally framed as a mechanical obstruction of the lumen causing infection, is now considered to be biological (or microbiological) given that, in select cases, it can be successfully treated with antibiotics,” wrote John Alverdy, MD, of the University of Chicago, in an accompanying editorial. “Under this new framework, it is reasonable to hypothesize that mind-body connections can influence the infectious process based on emerging evidence in this field.”

However, he stated, “readers must be aware that rigorous molecular-based studies are needed to shift such descriptive-level observations” — as seen in the present analysis — “from remaining probabilistic so they become more deterministic.”

“These include the attitudes of the physicians, nurses, family members, etc., the pheromones they emit and share with one another, how these transferred signals are received and responded to, and how this giant ‘interactome’ mechanistically influences outcome,” noted Alverdy.

“Absent this information, we are left with associations that cannot be determined to be either causative nor actionable,” the editorialist concluded. “Unless we insist on complementary biology-level measurements and hard mechanistic-based evidence to support our clinical observations, it seems we are no better than homeopathic claims that declare ‘if you think you are better, then you are better.'”

For their study, Flum and colleagues examined data on a subset of 415 patients with acute appendicitis who had been randomized to receive antibiotics across 25 centers for the CODA trial from 2016 to 2020. All patients had completed a baseline survey on how successful they perceived antibiotics to be prior to knowing their assigned treatment group.

Mean age of patients in the analysis was 38.5 years, 65% were men, and nearly two-thirds were white. Over half had some education beyond high school, and the majority reported rarely or never seeking health literacy help.

Based on survey results, 27% felt antibiotics would be completely successful, 51% had an intermediate response, and 22% felt they would not be successful or were unsure.

Persistent signs and symptoms, seen in 33% overall, included fever, abdominal pain, chills, and tenderness. Almost three-quarters experienced symptoms for at least 1 day.

Analyses adjusted for sociodemographics, body mass index, appendiceal diameter, average pain within the last week, and health literacy.

Study limitations included the fact that beliefs were assessed after all received an informational pamphlet or viewed a video detailing the risks/benefits of treating appendicitis with antibiotics.