3.1 Baseline study population
719 patients were randomized to no visit (236), standard visit (246) or an enhanced visit (237). 713 completed the study with only 2 lost to follow up and 4 withdrawing from the study. () The majority of the subjects were white (82%) women (64.1%), with at least some college education (84%). The mean age was 33.7 years. Baseline distributions of age, gender, race, income, education and smoking status were similar in the three groups. (). There was no significant difference in subjects’ optimism or perceived stress at baseline. There was also no significant difference in symptom severity at baseline between groups (No visit WURSS-21; 41.84 (1.53), Standard Visit WURSS-21; 43.13 (1.61), Enhanced Visit WURSS-21; 42.87 (1.53)).
Flow diagram of study participants
3.2 Primary outcomes
Observed primary outcomes suggested modest reductions in patient reported severity and duration for the enhanced group, compared to no visit or standard as measured by the sample mean values. While not statistically significant, trends were consistent across duration and severity, and were in the direction hypothesized (). Mean duration of illness was 6.51 days in the enhanced group, compared to 6.96 in the standard visit and 6.75 in the no visit group. Between-group differences in area under the time severity curve followed the same trends, but were marginal.
Outcomes By Treatment Group (mean (std) followed by confidence interval)
Randomization to an enhanced patient-oriented clinical interaction led to a mean score of 45.6 on the CARE measure, compared to 35.4 in the standard group (p<0.001). The subjects rated 23/245 clinician encounters (9%) perfect on the CARE tool in the “standard” visit group while 89/235 (38%) rated the clinician perfect in the “enhanced” group (p<0.001)
Although variability was high and statistical significance was not reached, there was a graduated response with greater change of IL-8 and neutrophil counts from no visit to standard visit to enhanced visit. (, ) The length of the enhanced visit was also significantly longer than the standard visit by approximately 5 minutes (Standard 3:43, enhanced 8:34). ()
A: Change in IL-8 for “no visit,”“standard visit” and “enhanced visit” types.
Evaluation of the CARE scores revealed that the ability of perfect CARE scores to predict subsequent cold outcomes appeared even more robust with statistical significance. Of the 483 subjects seen by a clinician, 112 interactions were given a perfect score. Those subjects rating the clinician as perfect on the CARE empathy tool showed a reduction in patient reported cold severity by 17.4% compared to sub-perfect scores (Perfect: 223.4, sub-perfect: 270.6, p=0.04) and a reduction in duration by 1.11 days (Perfect: 5.89 days, sub-perfect: 7 days, p=0.003). (, ) Relationships were found only when perfect and sub-perfect scores were dichotomized with no clear “dose-response” effect.
Empathy Scores (CARE). Comparison between no visit, sub-perfect and perfect scores.
Kaplan-Meir Survival Curve showing time to end of cold for sub-perfect and perfect CARE scores.
The perfect CARE empathy score was also associated with a larger change in the immune markers IL-8 and neutrophil count when baseline levels were compared to levels approximately 48 hours later. () Subjects who gave the clinician a perfect score had a significantly higher change in both nasal neutrophils (sub-perfect: 11.93 vs. perfect: 49.42, p=0.09) and the cytokine, IL-8 (sub-perfect,: 72 vs perfect: 1585.5, p=0.02). ()
Including possible confounding variables (age, gender, race, education, optimism, perceived stress, time from first symptom to enrollment and randomization to pill and visit groups) in the assessment of perfect CARE score with severity and duration outcomes did not affect the direction or significance of the relationships. Among perfect score subjects, mean AUC values were 72.38 lower (p=0.018), and colds ended at a higher rate in the survival analysis (β=0.46, p=0.001). See Tables and for details.
Linear regression of overall cold severity (AUC)
Cox-proportional hazard model of rate at which colds are ending
3.3 Secondary outcomes
There were no statistically significant differences between the no-visit, standard and enhanced groups, or the no-visit, perfect and sub-perfect CARE score groups when the following was measured; optimism (LOT), perceived stress (PSS), mood states (Feeling thermometer) and the short form mental and physical assessment (SF-8; MCS, PCS).
Outcomes data did not suggest that there was any one practitioner who had high or low scores suggesting that there was not a significant practitioner effect among the six clinicians.