Identification of subgroups with differential treatment effects for longitudinal and multiresponse variables

We describe and evaluate a regression tree algorithm for finding subgroups with differential treatments effects in randomized trials with multivariate outcomes. The data may contain missing values in the outcomes and covariates, and the treatment variable is not limited to two levels. Simulation results show that the regression tree models have unbiased variable selection and the estimates of subgroup treatment effects are approximately unbiased. A bootstrap calibration technique is proposed for constructing confidence intervals for the treatment effects. The method is illustrated with data from a longitudinal study comparing two diabetes drugs and a mammography screening trial comparing two treatments and a control

Paced Respiration for Vasomotor and Other Menopausal Symptoms: A Randomized, Controlled Trial

poster abstractBackground: Paced respiration has been internationally recommended for vasomotor symptoms (e.g., hot flashes, night sweats) despite limited empirical evidence. Objective: To evaluate efficacy of a paced respiration intervention against breathing control and usual care control for vasomotor and other menopausal symptoms. Design: A 16-week, 3-group, partially blinded, controlled trial with 2:2:1 randomization and stratification by group (breast cancer, no cancer) was conducted in a Midwestern city and surrounding area. Participants: 218 randomized women (96 breast cancer survivors, 122 menopausal women without cancer) were recruited through community mailings and registries (29% minority). Interventions: Training, home practice support, and instructions to use the breathing at the time of each hot flash were delivered via compact disc with printed booklet (paced respiration intervention) or digital videodisc with printed booklet (fast shallow breathing control). Usual care control received a letter regarding group assignment. Main Measures: Outcomes included hot flash frequency, severity, and bother (primary), hot flash interference in daily life, perceived control over hot flashes, and mood and sleep disturbances (secondary). Intervention performance, adherence, and adverse events were assessed. Key Results: There were no significant group differences for primary outcomes at 8- or 16-weeks post-randomization. Most intervention participants did not achieve 50% reduction in vasomotor symptoms despite demonstrated ability to correctly do paced respiration and daily practice. Statistically significant differences in secondary outcomes at 8- and 16-weeks were small, not likely to be clinically relevant, and as likely to favor intervention as breathing control. Conclusions: Paced respiration is unlikely to provide clinical benefit for vasomotor or other menopausal symptoms in breast cancer survivors or menopausal women without cancer

SOMATOSENSORY AMPLIFICATION AND MENOPAUSAL SYMPTOMS IN BREAST CANCER SURVIVORS AND MIDLIFE WOMEN

OBJECTIVES Somatosensory amplification is the experience of sensing everyday bodily sensations as intense, agitating, and unpleasant. Using data from menopausal breast cancer survivors and midlife women without cancer, the study purposes were to (1) explore the psychometric properties of the Somatosensory Amplification Scale and (2) to describe somatosensory amplification and its relationship to menopausal symptoms of hot flashes, mood and sleep disturbance. STUDY DESIGN This was a cross-sectional, descriptive, correlational study using demographic, e-diary, and questionnaire data from 99 breast cancer survivors and 138 midlife women. MAIN OUTCOME MEASURES Somatosensory amplification, hot flashes (frequency, severity, bother, interference, perceived control), mood, and sleep. RESULTS Cronbach’s alphas for the scale were low. When an 8-item version of the scale was evaluated, alphas improved and item-total correlations remained strong or improved. Midlife women and breast cancer survivors did not have significantly different somatosensory amplification total or item scores after adjusting for group differences in demographics. Somatosensory amplification was significantly correlated with hot flash interference, perceived control over hot flashes, and mood and sleep disturbance in both groups but the patterns of correlations differed slightly between groups and depending on whether the 10-item or 8-item scale was used. CONCLUSION Somatosensory amplification may be a relevant concept to assess in relation to the menopausal symptom experience of midlife women with and without breast cancer as it may represent a potential intervention target to improve the menopausal symptom experience

Medication use in breast cancer survivors compared to midlife women.

PURPOSE: Many breast cancer survivors (BCS) take multiple medications for health problems associated with the treated cancer and other noncancer comorbidities. However, there is no published, large-scale descriptive evaluation of medication use in BCS compared to midlife women. The purpose of this study was (1) to compare the number and types of prescription medications and over-the-counter medications between BCS and midlife women without cancer and (2) to assess possible drug-drug interactions by evaluating the cytochrome P450 isoform properties of medications (inductors and inhibitors) in both groups. METHODS: A cross-sectional, descriptive, comparative design was used. Baseline data from 98 BCS and 138 midlife women without cancer was analyzed from a behavioral intervention trial for menopausal symptoms. RESULTS: BCS were taking significantly more prescription medications and a larger variety of different types of medication classifications (p < 0.05) after controlling for group differences (race, noncancer comorbid conditions, marital status, income, and smoking) in demographics. Twenty-four women were taking at least one medication considered to be a cytochrome P450 isoforms (CYP) inhibitor or inducer capable of clinical drug-drug interactions with no differences in CYP inhibitors or inducers found between groups. CONCLUSION: BCS are taking a vast array of medications during survivorship. It is unclear if prescription medications are managed by a single healthcare provider or several providers. Clinical implications are to monitor for possible interactions among the various prescription medications, over-the-counter medications, and supplements. Implications for behavioral and biomedical research are that clinical studies need to carefully assess and account for multiple medication uses. RELEVANCE OF THE STUDY: The findings of this study are relevant to research and practice for both oncology and general practitioners. The importance of assessing medication information provides information about symptom management in individuals surviving cancer. In addition, the potential interaction of drugs impacts efficacy of various treatments and impacts compliance by patients

Evaluating the role of serotonin in hot flashes after breast cancer using acute tryptophan depletion.

OBJECTIVE: Among women with breast cancer, hot flashes are frequent, severe, and bothersome symptoms that can negatively impact quality of life and compromise compliance with life-saving medications (eg, tamoxifen and aromatase inhibitors). Clinicians' abilities to treat hot flashes are limited due to inadequate understanding of physiological mechanisms involved in hot flashes. Using an acute tryptophan depletion paradigm, we tested whether alterations in central serotonin levels were involved in the induction of hot flashes in women with breast cancer. METHODS: This was a within-participant, double-blind, controlled, balanced, crossover study. Twenty-seven women completed two 9-hour test days. On one test day, women ingested a concentrated amino acid drink and encapsulated amino acids (no tryptophan) according to published procedures that have been shown to have specific effects on serotonin within 4.5 to 7 hours. On the other test day, women ingested a control drink. Serial venous blood sampling and objective hot flash monitoring were used to evaluate response to each condition. RESULTS: Response to acute tryptophan depletion was variable and unexplained by use of selective serotonin reuptake inhibitors, antiestrogens, breast cancer disease and treatment variables, or genetic polymorphisms in serotonin receptor and transporter genes. Contrary to our hypothesis, hot flashes were not worsened with acute tryptophan depletion. CONCLUSIONS: Physiologically documented and self-reported hot flashes were not exacerbated by tryptophan depletion. Additional mechanistic research is needed to better understand the etiology of hot flashes

The first 20 months of the COVID-19 pandemic: Mortality, intubation and ICU rates among 104,590 patients hospitalized at 21 United States health systems

Main objective There is limited information on how patient outcomes have changed during the COVID-19 pandemic. This study characterizes changes in mortality, intubation, and ICU admission rates during the first 20 months of the pandemic. Study design and methods University of Wisconsin researchers collected and harmonized electronic health record data from 1.1 million COVID-19 patients across 21 United States health systems from February 2020 through September 2021. The analysis comprised data from 104,590 adult hospitalized COVID-19 patients. Inclusion criteria for the analysis were: (1) age 18 years or older; (2) COVID-19 ICD-10 diagnosis during hospitalization and/or a positive COVID-19 PCR test in a 14-day window (+/- 7 days of hospital admission); and (3) health system contact prior to COVID-19 hospitalization. Outcomes assessed were: (1) mortality (primary), (2) endotracheal intubation, and (3) ICU admission. Results and significance The 104,590 hospitalized participants had a mean age of 61.7 years and were 50.4% female, 24% Black, and 56.8% White. Overall risk-standardized mortality (adjusted for age, sex, race, ethnicity, body mass index, insurance status and medical comorbidities) declined from 16% of hospitalized COVID-19 patients (95% CI: 16% to 17%) early in the pandemic (February-April 2020) to 9% (CI: 9% to 10%) later (July-September 2021). Among subpopulations, males (vs. females), those on Medicare (vs. those on commercial insurance), the severely obese (vs. normal weight), and those aged 60 and older (vs. younger individuals) had especially high mortality rates both early and late in the pandemic. ICU admission and intubation rates also declined across these 20 months. Conclusions Mortality, intubation, and ICU admission rates improved markedly over the first 20 months of the pandemic among adult hospitalized COVID-19 patients although gains varied by subpopulation. These data provide important information on the course of COVID-19 and identify hospitalized patient groups at heightened risk for negative outcomes. Trial registration ClinicalTrials.gov Identifier: NCT04506528 (https://clinicaltrials.gov/ct2/show/NCT04506528)

Paced Respiration for Vasomotor and Other Menopausal Symptoms: A Randomized, Controlled Trial

poster abstractBackground: Paced respiration has been internationally recommended for vasomotor symptoms (e.g., hot flashes, night sweats) despite limited empirical evidence. Objective: To evaluate efficacy of a paced respiration intervention against breathing control and usual care control for vasomotor and other menopausal symptoms. Design: A 16-week, 3-group, partially blinded, controlled trial with 2:2:1 randomization and stratification by group (breast cancer, no cancer) was conducted in a Midwestern city and surrounding area. Participants: 218 randomized women (96 breast cancer survivors, 122 menopausal women without cancer) were recruited through community mailings and registries (29% minority). Interventions: Training, home practice support, and instructions to use the breathing at the time of each hot flash were delivered via compact disc with printed booklet (paced respiration intervention) or digital videodisc with printed booklet (fast shallow breathing control). Usual care control received a letter regarding group assignment. Main Measures: Outcomes included hot flash frequency, severity, and bother (primary), hot flash interference in daily life, perceived control over hot flashes, and mood and sleep disturbances (secondary). Intervention performance, adherence, and adverse events were assessed. Key Results: There were no significant group differences for primary outcomes at 8- or 16-weeks post-randomization. Most intervention participants did not achieve 50% reduction in vasomotor symptoms despite demonstrated ability to correctly do paced respiration and daily practice. Statistically significant differences in secondary outcomes at 8- and 16-weeks were small, not likely to be clinically relevant, and as likely to favor intervention as breathing control. Conclusions: Paced respiration is unlikely to provide clinical benefit for vasomotor or other menopausal symptoms in breast cancer survivors or menopausal women without cancer