The role of spirituality in pain experiences among adults with cancer: an explanatory sequential mixed methods study.

PURPOSE: Foundational research demonstrates that spirituality may affect the way people with cancer experience pain. One potential route is through alterations in thoughts and beliefs, such as pain-related catastrophizing. The purpose of this study is to understand whether spirituality impacts pain experiences through pain-related catastrophizing. METHODS: This explanatory sequential mixed methods study was informed by an adapted Theory of Unpleasant Symptoms. Data were collected via online surveys (N = 79) and follow-up qualitative interviews (N = 25). Phase 1 employed Empirical Bayesian analysis. Phase 2 used deductive content analysis. Phase 3 involved creating a mixed methods joint display to integrate findings and draw meta inferences. RESULTS: Results indicate that total spiritual well-being was directly negatively associated with pain-related catastrophizing, and indirectly negatively associated with the outcomes of pain interference, pain severity, and pain-related distress. Qualitative categories highlight the supportive role of spirituality when facing pain, while also shedding light on the limitations of spirituality in the context of some pain (i.e., severe, neuropathic, and/or chronic). Mixed methods findings reveal the importance of spirituality for some people as they face cancer and cancer-related pain, as well as the need for integrating spirituality as part of a larger pain management plan. CONCLUSIONS: This research advances supportive cancer care by exploring the complex role of spirituality in pain experiences. Findings will inform further exploration into the role of spirituality in supporting holistic symptom management in the context of cancer, as well as developing and testing interventions to enhance spirituality and address symptom-related suffering.

The Role of Spirituality in Pain Experiences among Adults with Cancer: An Explanatory Sequential Mixed Methods Study.

Purpose: Foundational research demonstrates that spirituality may affect the way people with cancer experience pain. One potential route is through alterations in thoughts and beliefs, such as pain-related catastrophizing. The purpose of this study is to understand whether spirituality impacts pain experiences through pain-related catastrophizing. Methods: This explanatory sequential mixed methods study was informed by an adapted Theory of Unpleasant Symptoms. Data were collected via online surveys (N = 79) and follow-up qualitative interviews (N = 25). Phase 1 employed Empirical Bayesian analysis. Phase 2 used deductive content analysis. Phase 3 involved creating a mixed methods joint display to integrate findings and draw meta inferences. Results: Results indicate that spirituality was directly negatively associated with pain-related catastrophizing, and indirectly negatively associated with the outcomes of pain interference, pain severity, and pain-related distress. Qualitative categories highlight the supportive role of spirituality when facing pain, while also shedding light on the limitations of spirituality in the context of some pain (i.e., severe, neuropathic, and/or chronic). Mixed methods findings reveal the importance of spirituality for some people as they face cancer and cancer-related pain, as well as the need for integrating spirituality as part of a larger pain management plan. Conclusions: This research advances supportive cancer care by exploring the complex role of spirituality in pain experiences. Findings will inform further exploration into the role of spirituality in supporting holistic symptom management in the context of cancer, as well as developing and testing interventions to enhance spirituality and address symptom-related suffering.

Omega-3 fatty acids and autonomic function in adolescents with anorexia: A randomized trial.

OBJECTIVES: Patients with anorexia nervosa (AN) have autonomic nervous system (ANS) dysfunction as measured by heart rate variability (HRV). Omega-3 fatty acids may improve heart rate regulation. Our aim was to describe ANS response to a mid-day meal in adolescent females with AN in a 12-week treatment program, randomized to receive either omega-3 supplements or placebo. METHODS: This pilot study was a longitudinal, double-blind, randomized controlled trial. Each group was subdivided into an acutely ill cohort and a chronically ill cohort. Linear and non-linear measures of slope, mean, and pre/post-meal changes in HRV were measured at baseline, 6 weeks, and 12 weeks. RESULTS: Twenty-four women (n = 12 placebo; n = 12 omega-3) were enrolled. By program end, the acute omega-3 group alone showed no change in any pre-meal slope. Acute and chronic omega-3 groups, but not placebo groups, demonstrated physiologically expected post-meal heart rate increases at 12 weeks. For all measures at 6 and 12 weeks, the chronic placebo and omega-3 groups had smaller physiologic responses to the meal compared with the acute groups. CONCLUSIONS: Participation in a 12-week partial hospitalization program may improve autonomic function in response to mealtime, with possible additional benefit from omega-3 PUFA, particularly in those with acute illness. IMPACT: Autonomic function with meals improves with a 12-week partial hospitalization program in adolescent females with anorexia nervosa. Omega-3 polyunsaturated fatty acids may improve autonomic function, especially in adolescent females with acute forms of anorexia nervosa. Longer duration of illness in adolescent females with anorexia nervosa is associated with blunted autonomic response to meals.

Effects of Massage on Postoperative Pain in Infants With Complex Congenital Heart Disease.

BACKGROUND: Pain management is an essential component of care for pediatric patients following surgery. Massage reduces self-reported postoperative pain in adults with heart disease but has received little attention in postoperative pediatric patients with complex congenital heart disease (CCHD). OBJECTIVES: The aim of the study was to evaluate the effectiveness of massage compared to a rest period on postoperative pain scores and physiological responses in infants with CCHD. METHODS: We used a two-group randomized clinical trial design with a sample of 60 infants with CCHD between 1 day and 12 months of age following their first cardiothoracic surgery. Both groups received standard postoperative care. Group 1 received a daily 30-minute restriction of nonessential caregiving (quiet time), and Group 2 received a daily 30-minute massage. Interventions continued for seven consecutive days. Pain was measured six times daily using the Face, Legs, Activity, Cry, Consolability Pain Assessment Tool (FLACC). Average daily doses of analgesics were recorded. Heart rates (HRs), respiratory rates (RRs), and oxygen saturations (SpO2) were recorded continuously. Daily averages, pre- and postintervention FLACC scores, and physiological responses were analyzed using descriptive statistics, generalized linear mixed models repeated measures, latent growth models, and/or regression discontinuity analysis. Fentanyl-equivalent narcotic values were used as a time-varying covariate. RESULTS: Adjusted pain scores were lower for the massage group on all days except Day 7. Overall, there were no group effects on level of pain or differential rate of change in pain. However, the massage group had lower daily pain scores with small to medium effect size differences, largest at Days 4, 5, and 6, and lower average daily HR and RR. There was little difference between groups in SpO2. Infants demonstrated immediate effects of massage, with HR and RR decreasing and oxygen saturations increasing. DISCUSSION: This study provides beginning evidence that postoperative massage may reduce pain and improve physiological parameters in infants with congenital heart disease. This nonpharmacological adjunct to pain management may provide a particular benefit for this population by reducing demand on the cardiorespiratory system.

Mindfulness meditation and exercise both improve sleep quality: Secondary analysis of a randomized controlled trial of community dwelling adults.

OBJECTIVES: To assess the benefits of training in mindfulness-based stress reduction (MBSR) or moderate intensity exercise (EX) for improving sleep quality. DESIGN: Randomized controlled trial. SETTING: Outpatient, community-based. PARTICIPANTS: Healthy adults (n = 413) aged 30-69 who did not regularly exercise or practice meditation, and who had no known prior sleep problems. INTERVENTIONS: 1) 8-weeks of MBSR training; 2) matched EX training; or 3) wait-list control. MEASUREMENTS: The Pittsburgh Sleep Quality Index (PSQI) was administered at baseline and at 1, 3, 5, and 7-month follow-up visits. ANALYSIS: Total PSQI scores and three PSQI factors (perceived sleep quality; daily disturbance, sleep efficiency) were assessed using linear mixed effects regression models for longitudinal data. RESULTS: Compared to controls, PSQI global scores improved significantly for EX (mean change -0.98 points [95% CI -1.56, -0.41] p = 0.001) and marginally for MBSR (-0.53 [-1.10, 0.04] p = 0.07). The perceived sleep quality factor improved for both EX (-0.18 [-0.30, -0.07] p = 0.002) and MBSR (-0.12 [-0.24, -0.01] p = 0.035). The daily disturbance factor improved slightly more for MBSR (-0.13 [-0.22, -0.033] p = 0.008) than EX (-0.09 [-0.19, 0.004] p = 0.06). The sleep efficiency factor did not improve after MBSR (0.08 [-0.045, 0.21] p = 0.2) or EX (-0.07 [-0.20, 0.06] p = 0.3). Improvements in the sleep quality were sustained over 7 months for both groups. CONCLUSIONS: Training in MBSR and EX produced small but statistically significant and sustained improvements in sleep quality. For EX participants, this improvement was due primarily to improvements in perceived sleep quality. For MBSR, the decrease in daily disturbance was more important.

Mediational pathways of meditation and exercise on mental health and perceived stress: A randomized controlled trial.

This study investigated the effects of mindfulness and exercise training on indicators of mental health and stress by examining shared mediators of program effects. Community-recruited adults (N = 413) were randomized into one of three conditions: (a) mindfulness-based stress reduction, (b) moderate intensity exercise, or (c) wait-list control. Composite indicator structural equation models estimated direct, indirect, and total effects. Results showed that mindfulness-based self-efficacy fulfilled a prominent role in mediating meditation and exercise program effects. Findings suggest that mindfulness and exercise training share similar mechanisms that can improve global mental health, including adaptive responses to stress.

Neonatal Skin-to-Skin Contact: Implications for Learning and Autonomic Nervous System Function in Infants With Congenital Heart Disease.

BACKGROUND: Infants with complex congenital heart disease (CCHD) often develop neurodevelopmental disabilities. Cognitive abilities are associated with vagally mediated autonomic function. Skin-to-skin contact (SSC) interventions enhance infant neurodevelopment and autonomic function in other high-risk populations. AIM: To examine the effects of a neonatal SSC intervention on learning and autonomic function in 3-month-old infants: infants with CCHD who received neonatal SSC ( n = 10), typically developing (TD) infants ( n = 16), and infants with CCHD without SSC ( n = 10). METHODS: This secondary data analysis measured cognitive function using the mobile paradigm (MP), a classic measure of learning based on operant conditioning. Autonomic function was assessed with heart rate (HR) and HR variability (HRV). Data were analyzed with repeated-measures general linear mixed modeling with α = .10 for this exploratory study. RESULTS: Learning rates were TD = 75%, cardiac-SSC = 70%, and cardiac-control = 40%. Learners demonstrated significant reductions in HRV during the MP; nonlearners exhibited no change. TD and cardiac-SSC groups exhibited increases in HR and reductions in HRV during the MP. No significant changes occurred in the cardiac-control group. Nonlinear HRV during the MP differed only in the TD group. CONCLUSIONS: Findings suggest improvements in cognitive and autonomic development in 3-month-old infants with CCHD who received neonatal SSC. Learning and autonomic function results in infants with CCHD who had not received SSC suggest reduced capacity to muster the physiologic resources to carry out this cognitive task. Findings provide preliminary evidence in support of implementation of SSC with infants with CCHD and support additional research.

Predictors of Mindfulness Meditation and Exercise Practice, from MEPARI-2, a randomized controlled trial.

OBJECTIVES: Health-supporting behaviors can be challenging to initiate and maintain. Data from the MEPARI-2 randomized trial were used to assess predictors of sustained exercise and meditation practice. METHODS: Adults aged 30 to 69 years not exercising regularly and without prior meditation training were randomized to 8-week trainings in mindfulness meditation, moderate intensity exercise, or observational control, and monitored for 8 months. Exercise participants reported day-to-day minutes of moderate and vigorous activity; mindfulness meditation participants reported minutes of informal and formal practice. Demographic characteristics and psychosocial factors were assessed as predictors of practice. Growth mixture modeling was used to identify higher and lower practice subgroups. RESULTS: 413 participants (75.8% female; mean (SD) age 49.7 (11.6) years) were randomized to exercise (137), mindfulness meditation (138), or control (138), with 390 (95%) completing the study. Seventy-nine percent of exercisers and 62% of meditators reported ≥150 minutes/week practice for at least half of the 37 weeks monitored. Self-reported minutes of mindfulness meditation and/or exercise practice were significantly (p<0.01) predicted by baseline levels of: general mental health, self-efficacy, perceived stress, depressive symptoms, openness, neuroticism, physical activity, smoking status, and number of social contacts. Growth mixture modeling identified subsets of people with moderate (100-200 min/week) and high (300-450 min/week) levels of self-reported practice for both mindfulness meditation (62% moderate; 38% high) and exercise (71% moderate; 29% high). CONCLUSIONS: In this sample, participants randomized to behavioral trainings reported high levels of practice sustained over 37 weeks. Baseline psychosocial measures predicted practice levels in expected directions.

Meditation or exercise for preventing acute respiratory infection (MEPARI-2): A randomized controlled trial.

BACKGROUND: Practice of meditation or exercise may enhance health to protect against acute infectious illness. OBJECTIVE: To assess preventive effects of meditation and exercise on acute respiratory infection (ARI) illness. DESIGN: Randomized controlled prevention trial with three parallel groups. SETTING: Madison, Wisconsin, USA. PARTICIPANTS: Community-recruited adults who did not regularly exercise or meditate. METHODS: 1) 8-week behavioral training in mindfulness-based stress reduction (MBSR); 2) matched 8-week training in moderate intensity sustained exercise (EX); or 3) observational waitlist control. Training classes occurred in September and October, with weekly ARI surveillance through May. Incidence, duration, and area-under-curve ARI global severity were measured using daily reports on the WURSS-24 during ARI illness. Viruses were identified multiplex PCR. Absenteeism, health care utilization, and psychosocial health self-report assessments were also employed. RESULTS: Of 413 participants randomized, 390 completed the trial. In the MBSR group, 74 experienced 112 ARI episodes with 1045 days of ARI illness. Among exercisers, 84 had 120 episodes totaling 1010 illness days. Eighty-two of the controls had 134 episodes with 1210 days of ARI illness. Mean global severity was 315 for MBSR (95% confidence interval 244, 386), 256 (193, 318) for EX, and 336 (268, 403) for controls. A prespecified multivariate zero-inflated regression model suggested reduced incidence for MBSR (p = 0.036) and lower global severity for EX (p = 0.042), compared to control, not quite attaining the p<0.025 prespecified cut-off for null hypothesis rejection. There were 73 ARI-related missed-work days and 22 ARI-related health care visits in the MBSR group, 82 days and 21 visits for exercisers, and 105 days and 24 visits among controls. Viruses were identified in 63 ARI episodes in the MBSR group, compared to 64 for EX and 72 for control. Statistically significant (p<0.05) improvements in general mental health, self-efficacy, mindful attention, sleep quality, perceived stress, and depressive symptoms were observed in the MBSR and/or EX groups, compared to control. CONCLUSIONS: Training in mindfulness meditation or exercise may help protect against ARI illness. LIMITATIONS: This trial was likely underpowered. TRIAL REGISTRATION: Clinicaltrials.gov NCT01654289.

Autonomic Nervous System Function After a Skin-to-Skin Contact Intervention in Infants With Congenital Heart Disease.

BACKGROUND: Infants with complex congenital heart disease (CCHD) demonstrate impaired autonomic nervous system (ANS) regulation, which may contribute to commonly observed impairments in feeding, growth, and development. Close mother-infant physical contact improves ANS function in other high-risk infant populations. OBJECTIVE: Our purposes were to examine feasibility of a 2-week daily skin-to-skin contact (SSC) intervention and to describe change in ANS function in response to the intervention. METHODS: Feasibility was assessed by recruitment and retention rates, safety, and acceptability. Autonomic nervous system function was measured with linear and nonlinear measures of heart rate variability (HRV) during a feeding before the 14-day SSC intervention and 3 times during a 4-week follow-up. RESULTS: Recruitment rate was 72%; retention rate was 55.5%. Mothers were universally positive about SSC. Ten mothers and infants completed a daily mean of 77.05 minutes of SSC during the 14-day intervention with no adverse events. Baseline high-frequency HRV, reactivity to challenge, and recovery after challenge improved during the 6-week study. Nonlinear measures demonstrated abnormally high sympathetic activity, especially after feeding, in most infants. CONCLUSIONS: Skin-to-skin contact is feasible in infants with CCHD. Linear measures of HRV suggested improvements in ANS function with this intervention. This article is one of the first to describe nonlinear HRV measures in infants with CCHD. Additional research is needed to identify variations in linear and nonlinear effects based on specific cardiac conditions and with varying intervention doses and timing. This low-cost, low-risk intervention has the potential to improve outcomes in infants with CCHD.

Angiogenic effects of borate glass microfibers in a rodent model.

The primary objective of this research was to evaluate the use of bioactive borate-based glass microfibers for angiogenesis in soft tissue repair applications. The effect of these fibers on growth of capillaries and small blood vessels was compared to that of 45S5 silica glass microfibers and sham implant controls. Compressed mats of three types of glass microfibers were implanted subcutaneously in rats and tissues surrounding the implant sites histologically evaluated 2-4 weeks post surgery. Bioactive borate glass 13-93B3 supplemented with 0.4 wt % copper promoted extensive angiogenesis as compared to silica glass microfibers and sham control tissues. The angiogenic responses suggest the copper-containing 13-93B3 microfibers may be effective for treating chronic soft tissue wounds. A second objective was to assess the possible systemic cytotoxicity of dissolved borate ions and other materials released from implanted borate glass microfibers. Cytotoxicity was assessed via histological evaluation of kidney tissue collected from animals 4 weeks after subcutaneously implanting high amounts of the borate glass microfibers. The evaluation of the kidney tissue from these animals showed no evidence of chronic histopathological changes in the kidney. The overall results indicate the borate glass microfibers are safe and effective for soft tissue applications.

Impact of an internet-based intervention on Finnish mothers' perceptions of parenting satisfaction, infant centrality and depressive symptoms during the postpartum year.

OBJECTIVE: this study evaluates how an internet-based intervention affects mothers' parenting satisfaction, infant centrality and depressive symptoms. DESIGN: a quasi-experimental design and repeated measures were used. SETTINGS: this study was conducted in two Finnish public maternity hospitals (intervention/control). PARTICIPANTS: a convenience sample (N=1300) of primiparous and multiparous Finnish-speaking mothers were invited to participate. Multiple-birth and early discharge mothers receiving home visits were excluded. The analysis included 760 mothers. INTERVENTION: the intervention offered online support for parenting, breast feeding and infant care beginning from the middle of pregnancy. It consisted of an information database, a peer discussion forum and expert advice. MEASUREMENTS: Outcomes were measured by the Evaluation and Infant Centrality subscales of the What Being the Parent of a New Baby is Like-Revised, and the Edinburgh Postnatal Depression Scale after childbirth, and six weeks, six months and 12 months post partum. Age, parity, parenting self-efficacy, and perception of infant and family functioning were used as the covariates. FINDINGS: during the first postpartum year, mothers' parenting satisfaction increased significantly, whereas infant centrality and depressive symptoms decreased within groups. However, these changes were not linear. The mean difference between groups in parenting satisfaction and depressive symptoms was not significant within any of the four assessments. The mean difference in infant centrality between control and intervention mothers was significant only at six weeks post partum. Primiparas scored significantly higher in infant centrality and significantly lower in depressive symptoms than multiparas. KEY CONCLUSION AND IMPLICATIONS FOR PRACTICE: an internet-based intervention did not significantly affect mothers' perceptions of parenting satisfaction and depressive symptoms, but intervention mothers experienced higher infant centrality compared with control mothers at six weeks. Parenting self-efficacy was a significant covariate for all measures. Parity needs to be taken into account when infant centrality and depressive symptoms are used as outcome variables in intervention studies. More research is needed to study the potential of information data bank, professional, and peer online support. This study also highlights the need to pay more attention to the selection of the target population, the selection of outcome measures, and implementation issues in intervention research.

Randomized controlled trial of mindfulness meditation and exercise for the prevention of acute respiratory infection: possible mechanisms of action.

Background. A randomized trial suggests that meditation and exercise may prevent acute respiratory infection (ARI). This paper explores potential mediating mechanisms. Methods. Community-recruited adults were randomly assigned to three nonblinded arms: 8-week mindfulness-based stress reduction (N = 51), moderate-intensity exercise (N = 51), or wait-list control (N = 52). Primary outcomes were ARI illness burden (validated Wisconsin Upper Respiratory Symptom Survey). Potential mediators included self-reported psychophysical health and exercise intensity (baseline, 9 weeks, and 3 months). A Baron and Kenny approach-based mediational analysis model, adjusted for group status, age, and gender, evaluated the relationship between the primary outcome and a potential mediator using zero-inflated modeling and Sobel testing. Results. Of 154 randomized, 149 completed the trial (51, 47, and 51 in meditation, exercise, and control groups) and were analyzed (82% female, 94% Caucasian, 59.3 ± SD 6.6 years old). Mediational analyses suggested that improved mindfulness (Mindful Attention Awareness Scale) at 3 months may mediate intervention effects on ARI severity and duration (P < 0.05); 1 point increase in the mindfulness score corresponded to a shortened ARI duration by 7.2-9.6 hours. Conclusions. Meditation and exercise may decrease the ARI illness burden through increased mindfulness. These preliminary findings need confirmation, if confirmed, they would have important policy and clinical implications. This trial registration was Clinicaltrials.gov: NCT01057771.

Advantage of meditation over exercise in reducing cold and flu illness is related to improved function and quality of life.

PURPOSE: To examine whether apparent advantages following training in meditation over exercise can be attributed to specific symptoms, functional impairments, or quality-of-life indicators assessed by the Wisconsin Upper Respiratory Symptom Survey (WURSS-24). METHODS: Results from the randomized controlled trial "Meditation or Exercise for Preventing Acute Respiratory Illness" showed mean global severity and total days of illness were worse in control (358, 8·9) compared with exercise (248, 5·1) or meditation (144, 5·0). Global severity of illness was estimated using area under the curve from daily self-reported severity scores on the WURSS-24. For this project, we estimated within-group WURSS item-level severity and between-group effect sizes (Cohen's "d" statistic) relative to control. The item-level effect sizes were grouped into (i) symptom and (ii) function and quality of life domains. RESULTS: Among the three groups, mediators showed the lowest severity estimates for 21 of 22 WURSS items. Item-level Cohen's "d" indicated most benefit was evident in WURSS items representing function and quality of life. Compared with exercise, meditation fostered larger reductions in illness severity, although due mostly to improved function and the quality of life domain (d=-0·33, P<0·001) compared with symptom domain (d=-0·22, P<0·001). CONCLUSIONS: The apparent advantage of training in meditation over exercise for reducing cold and flu illness is explained more by improved function and quality of life than by a reduction in symptom severity.

Meditation or exercise for preventing acute respiratory infection: a randomized controlled trial.

PURPOSE: This study was designed to evaluate potential preventive effects of meditation or exercise on incidence, duration, and severity of acute respiratory infection (ARI) illness. METHODS: Community-recruited adults aged 50 years and older were randomized to 1 of 3 study groups: 8-week training in mindfulness meditation, matched 8-week training in moderate-intensity sustained exercise, or observational control. The primary outcome was area-under-the-curve global illness severity during a single cold and influenza season, using the Wisconsin Upper Respiratory Symptom Survey (WURSS-24) to assess severity. Health care visits and days of missed work were counted. Nasal wash collected during ARI illness was assayed for neutrophils, interleukin-8, and viral nucleic acid. RESULTS: Of 154 adults randomized into the study, 149 completed the trial (82% female, 94% white, mean age 59.3 ± 6.6 years). There were 27 ARI episodes and 257 days of ARI illness in the meditation group (n = 51), 26 episodes and 241 illness days in the exercise group (n = 47), and 40 episodes and 453 days in the control group (n = 51). Mean global severity was 144 for meditation, 248 for exercise, and 358 for control. Compared with control, global severity was significantly lower for meditation (P = .004). Both global severity and total days of illness (duration) trended toward being lower for the exercise group (P=.16 and P=.032, respectively), as did illness duration for the meditation group (P=.034). Adjusting for covariates using zero-inflated multivariate regression models gave similar results. There were 67 ARI-related days of-work missed in the control group, 32 in the exercise group (P = .041), and 16 in the meditation group (P <.001). Health care visits did not differ significantly. Viruses were identified in 54% of samples from meditation, 42% from exercise, and 54% from control groups. Neutrophil count and interleukin-8 levels were similar among intervention groups. CONCLUSIONS: Training in meditation or exercise may be effective in reducing ARI illness burden.

Placebo effects and the common cold: a randomized controlled trial.

PURPOSE: We wanted to determine whether the severity and duration of illness caused by the common cold are influenced by randomized assignment to open-label pills, compared with conventional double-blind allocation to active and placebo pills, compared with no pills at all. METHODS: We undertook a randomized controlled trial among a population with new-onset common cold. Study participants were allocated to 4 parallel groups: (1) those receiving no pills, (2) those blinded to placebo, (3) those blinded to echinacea, and (4) those given open-label echinacea. Primary outcomes were illness duration and area-under-the-curve global severity. Secondary outcomes included neutrophil count and interleukin 8 levels from nasal wash at intake and 2 days later. RESULTS: Of 719 randomized study participants, 2 were lost and 4 exited early. Participants were 64% female, 88% white, and aged 12 to 80 years. Mean illness duration for each group was 7.03 days for those in the no-pill group, 6.87 days for those blinded to placebo, 6.34 days for those blinded to echinacea, and 6.76 days for those in the open-label echinacea group. Mean global severity scores for the 4 groups were no pills, 286; blinded to placebo, 264; blinded to echinacea, 236; and open-label echinacea, 258. Between-group differences were not statistically significant. Comparing the no-pill with blinded to placebo groups, differences (95% confidence interval [CI]) were -0.16 days (95% CI, -0.90 to 0.58 days) for illness duration and -22 severity points (95% CI, -70 to 26 points) for global severity. Comparing the group blinded to echinacea with the open-label echinacea group, differences were 0.42 days (95% CI, -0.28 to 1.12 days) and 22 severity points (95% CI, -19 to 63 points). Median change in interleukin 8 concentration and neutrophil cell count, respectively by group, were 30 pg/mL and 1 cell for the no-pill group, 39 pg/mL and 1 cell for the group binded to placebo, 58 pg/mL and 2 cells for the group blinded to echinacea, and 70 pg/mL and 1 cell for the group with open-label echinacea, also not statistically significant. Among the 120 participants who at intake rated echinacea's effectiveness as greater than 50 on a 100-point scale for which 100 is extremely effective, illness duration was 2.58 days shorter (95% CI, -4.47 to -0.68 days) in those blinded to placebo rather than no pill, and mean global severity score was 26% lower but not significantly different (-97.0, 95% CI, -249.8 to 55.8 points). In this subgroup, neither duration nor severity differed significantly between the group blinded to echinacea and the open-label echinacea group. CONCLUSIONS: Participants randomized to the no-pill group tended to have longer and more severe illnesses than those who received pills. For the subgroup who believed in echinacea and received pills, illnesses were substantively shorter and less severe, regardless of whether the pills contained echinacea. These findings support the general idea that beliefs and feelings about treatments may be important and perhaps should be taken into consideration when making medical decisions.

Echinacea for treating the common cold: a randomized trial.

BACKGROUND: Echinacea is widely used to treat the common cold. OBJECTIVE: To assess the potential benefits of echinacea as a treatment of common cold. DESIGN: Randomized, controlled trial. (ClinicalTrials.gov registration number: NCT00065715) SETTING: Dane County, Wisconsin. PATIENTS: 719 patients, aged 12 to 80 years, with new-onset common cold. INTERVENTION: Patients were assigned to 1 of 4 parallel groups: no pills, placebo pills (blinded), echinacea pills (blinded), or echinacea pills (unblinded, open-label). Echinacea groups received the equivalent of 10.2 g of dried echinacea root during the first 24 hours and 5.1 g during each of the next 4 days. Indistinguishable placebo tablets contained only inert ingredients. MEASUREMENTS: The primary outcome was the area under the curve for global severity, with severity assessed twice daily by self-report using the Wisconsin Upper Respiratory Symptom Survey, short version. Secondary outcomes included interleukin-8 levels and neutrophil counts from nasal wash, assessed at intake and 2 days later. RESULTS: Of the 719 patients enrolled, 713 completed the protocol. Mean age was 33.7 years, 64% were female, and 88% were white. Mean global severity was 236 and 258 for the blinded and unblinded echinacea groups, respectively; 264 for the blinded placebo group; and 286 for the no-pill group. A comparison of the 2 blinded groups showed a 28-point trend (95% CI, -69 to 13 points) toward benefit for echinacea (P = 0.089). Mean illness duration in the blinded and unblinded echinacea groups was 6.34 and 6.76 days, respectively, compared with 6.87 days in the blinded placebo group and 7.03 days in the no-pill group. A comparison of the blinded groups showed a nonsignificant 0.53-day (CI, -1.25 to 0.19 days) benefit (P = 0.075). Median change in interleukin-8 levels and neutrophil counts were also not statistically significant (30 ng/L and 1 cell/high-power field [hpf] in the no-pill group, 39 ng/L and 1 cell/hpf in the blinded placebo group, 58 ng/L and 2 cells/hpf in the blinded echinacea group, and 70 ng/L and 1 cell/hpf in the open-label echinacea group). LIMITATION: Higher-than-expected variability limited power to detect small benefits. CONCLUSION: Illness duration and severity were not statistically significant with echinacea compared with placebo. These results do not support the ability of this dose of the echinacea formulation to substantively change the course of the common cold. PRIMARY FUNDING SOURCE: National Center for Complementary and Alternative Medicine, National Institutes of Health.

Rationale and methods for a trial assessing placebo, echinacea, and doctor-patient interaction in the common cold.

BACKGROUND: Clinical medicine and healthcare policy are increasingly guided by randomized controlled trials, which in turn are dependent on the validity of placebo control. It is important to understand the effects of placebo control on outcome measurement, especially for assessment of symptoms and functional impairments where subjectivity, expectancy, and motivation may significantly impact outcome evaluation. This paper describes the rationale and methodology of a trial designed to evaluate placebo effects related to taking pills and to compare these with effects attributable to standard or enhanced (patient-oriented) doctor-patient interaction. DESIGN: This trial uses two-way factorial allocation to randomize people with new onset common cold in two directions: pill related and doctor related. In one direction, participants are randomized to (1) no pills, (2) blinded placebo, (3) blinded echinacea, or (4) unblinded open-label echinacea. In the other direction, participants are randomized to: (1) no doctor-patient interaction, (2) standard doctor-patient interaction, and (3) enhanced doctor-patient interaction. Enhanced interaction includes education, empathy, empowerment, positive prognosis, and connectedness. Area under the time severity curve is the primary outcome, with the Wisconsin Upper Respiratory Symptom Survey (WURSS-21) the measure of severity. A priori power studies called for a sample size of N = 720 trial finishers to detect 15% to 20% between-group differences in this outcome. Secondary outcomes include general health-related quality of life, perceived stress, interpersonal support, optimism, patient satisfaction, and positive and negative affectivity. Two biomarkers are also assessed: interleukin-8 (inflammatory cytokine) and neutrophil count from nasal wash. IMPORTANCE: This paper describes the rationale and methodology of a trial assessing placebo effects related to pills and to doctor-patient interaction. This is one of very few similar studies and is the first in the common cold. Data collected will also provide an excellent opportunity to investigate relationships among demographic (age, sex, education, income) and psychosocial (perceived stress, interpersonal support, optimism, affectivity) indicators in relation to common cold outcomes.

Sufficiently important difference for common cold: severity reduction.

PURPOSE: We undertook a study to estimate the sufficiently important difference (SID) for the common cold. The SID is the smallest benefit that an intervention would require to justify costs and risks. METHODS: Benefit-harm tradeoff interviews (in-person and telephone) assessed SID in terms of overall severity reduction using evidence-based simple-language scenarios for 4 common cold treatments: vitamin C, the herbal medicine echinacea, zinc lozenges, and the unlicensed antiviral pleconaril. RESULTS: Response patterns to the 4 scenarios in the telephone and in-person samples were not statistically distinguishable and were merged for most analyses. The scenario based on vitamin C led to a mean SID of 25% (95% confidence interval [CI] 0.23-0.27). For the echinacea-based scenario, mean SID was 32% (95% CI, 0.30-0.34). For the zinc-based scenario, mean SID was 47% (95% CI, 0.43-0.51). The scenario based on preliminary antiviral trials provided a mean SID of 57% (95% CI, 0.53-0.61). Multivariate analyses suggested that (1) between-scenario differences were substantive and reproducible in the 2 samples, (2) presence or severity of illness did not predict SID, and (3) SID was not influenced by age, sex, tobacco use, ethnicity, income, or education. Despite consistencies supporting the model and methods, response patterns were diverse, with wide spreads of individual SID values within and among treatment scenarios. CONCLUSIONS: Depending on treatment specifics, people want an on-average 25% to 57% reduction in overall illness severity to justify costs and risks of popular cold treatments. Randomized trial evidence does not support benefits this large. This model and these methods should be further developed for use in other disease entities.

Using benefit harm tradeoffs to estimate sufficiently important difference: the case of the common cold.

CONTEXT: The term "sufficiently important difference" (SID) refers to the overall amount of benefit that people consider sufficient to justify the costs and risks of treatment. Little is known about patient preferences regarding benefits and harms of common cold treatments. OBJECTIVES: To develop methods to assess SID and to estimate SID for common cold. DESIGN: The authors conducted in-person and telephone interviews with people with colds, using benefit harm tradeoff methods. The hypothetical benefit of reduction in length of illness was traded off against best estimates of costs and risks. First, the authors briefly described costs, risks, and possible symptomatic benefits of 4 treatment scenarios, based on evidence regarding vitamin C, echinacea, zinc, and pleconaril, an antiviral. Hypothetical benefit (reduction of illness duration) was then varied until the cold sufferer indicated that the treatment was minimally desirable. PARTICIPANTS: Interviews were conducted in person with 149 community-recruited adult participants, once at the beginning of their colds, and then again within a few days after symptoms had resolved. Additionally, 162 adult callers with self-identified colds completed interviews via telephone. RESULTS: A total of 460 benefit harm tradeoff interviews (1840 treatment scenarios) estimated overall mean SID as 52.6 h (95% CI, 50.6 to 54.6). For the scenario based on vitamin C, mean SID was estimated as 26.1 h (95% CI, 23.2 to 29.3), with 142 of 460 (31%) saying they would take it regardless of duration benefit, and 22 of 460 (5%) saying they would not take it, regardless of duration benefit. For the echinacea-based scenario, mean SID was estimated at 36.8 h (33.4 to 40.2), with 105 (23%) favoring and 41 (9%) rejecting treatment, regardless of duration benefit. For the zinc lozenge-based scenario, mean SID was estimated as 64.8 h (61.0 to 67.9), with 42 (9%) favoring and 109 (24%) rejecting treatment. For the prescription antiviral-based scenario, mean SID was estimated as 82.6 h (78.7 to 86.7), with 29 (6%) favoring and 223 (48%) rejecting. Severity of illness at the time of interview did not appear to significantly influence responses. Possible side effects, treatment type (tablet v. lozenge v. liquid), monetary costs, and opportunity costs (e.g., getting to the doctor or pharmacy, dosing frequency) did appear to be important in influencing these preference patterns. CONCLUSIONS: Our study suggests that, on average, people want the duration of their colds to be reduced by between 26 and 65 h to justify potential harms of popular cold treatments. A prescription antiviral would require a greater benefit (83 h) to justify larger perceived risks.