SLEEP DISTURBANCE IN INDIVIDUALS DIAGNOSED WITH COLORECTAL CANCER: FACTORS ASSOCIATED WITH SLEEP DISTURBANCE AND CHANGES IN SLEEP DISTURBANCE

This dissertation evaluates sleep disturbance in individuals with colorectal cancer (CRC), with the objectives of providing insight on the patient, disease and treatment characteristics associated with sleep disturbance (and change in sleep disturbance), investigating whether there is variation in these factors across levels of sleep disturbance severity (and change in sleep disturbance severity), and finally assessing the relationship between sleep disturbance (and change in sleep disturbance) and exercise (and change in exercise). We also investigated possible heterogeneity in the relationship between sleep disturbance and these factors. Data were obtained from the MY-Health study, a community-based observational study of adults diagnosed with cancer collected through four Surveillance, Epidemiology and End Results (SEER) cancer registries. Patient-Reported Outcomes Measurement Information System (PROMIS) measures were administered to patients to measure sleep, anxiety, depression, fatigue, pain interference, and social and physical functioning. Participants (n = 734) self-reported demographic information, comorbidities, treatment type, and dates of treatment. Data were collected at two time points after diagnosis: approximately 10 and 17 months after diagnosis. Regression mixture models (RMM) (to evaluate heterogeneity) and multiple regression models were used to evaluate the relationship between sleep disturbance and patient, disease, and treatment factors, as well as exercise. Overall, results of the RMM analyses provided evidence that the relationship between sleep disturbance and patient, disease, treatment characteristics, and exercise levels was consistent at every severity level of sleep disturbance. Factors yielding statistically significant relationships with sleep disturbance at approximately 10 months after CRC were 2 or more comorbid conditions, non-retirees, anxiety, pain interference, and fatigue. Change in anxiety and fatigue yielded statistically significant relationships with change in sleep disturbance. Coefficients were small; CRC patients should be screened for sleep disturbance throughout the cancer continuum. We found no relationship between exercise approximately at or above American College of Sports Medicine guidelines and sleep disturbance at approximately 10 and 17 months after CRC diagnosis (or change increase in exercise and change in sleep disturbance). Exercise has clear health benefits and although this study does not provide evidence that exercise is associated with better sleep quality, CRC patients should continue to be encouraged to exercise.Doctor of Philosoph

Sleep quality in individuals diagnosed with colorectal cancer: Factors associated with sleep disturbance as patients transition off treatment

To identify patient characteristics associated with sleep disturbance and worsening of sleep in individuals diagnosed with localized colorectal cancer and assess heterogeneity in these relationships. Methods: Data were from the MY-Health study, a community-based observational study of adults diagnosed with cancer. Patient-Reported Outcomes Measurement Information System® Sleep Disturbance, Anxiety, Depression, Fatigue, and Pain Interference measures were administered. Participants self-reported demographics, comorbidities, and treatment information. Regression mixture and multiple regression models were used to evaluate the relationship between sleep disturbance and patient characteristics cross-sectionally at an average of 10 months after diagnosis (n = 613) as well as change in sleep disturbance over a 6-month period (n = 361). Results: Pain, anxiety, fatigue, and the existence of multiple comorbid conditions had statistically significant relationships with sleep disturbance (B = 0.09, 0.22, 0.29, and 1.53, respectively; P < 0.05). Retirement (B = -2.49) was associated with sleep quality in the cross-sectional model. Worsening anxiety (B = 0.14) and fatigue (B = 0.20) were associated with worsening sleep disturbance, and more severe sleep disturbance 10 months after diagnosis (B = -0.21) was associated with improvement in sleep quality after diagnosis (P < 0.05). No evidence of latent subgroups of patients (heterogeneity) was present. Conclusions: Pain, anxiety, fatigue, employment, and comorbid conditions were associated with sleep disturbance, but regression coefficients were small (< |2.5|). Results suggest that screening for anxiety, depression, fatigue, or pain is not sufficient for identifying sleep disturbance. Given the negative consequences of sleep disturbance, sleep disturbance screening may be warranted

Relationship between sleep and exercise as colorectal cancer survivors transition off treatment

Purpose The primary objective of this study was to evaluate the relationship between exercise and sleep disturbance in a sample of individuals diagnosed with stage I, II, and III colorectal cancer (CRC) as patients transitioned off first-line treatment. We also sought to identify heterogeneity in the relationship between sleep disturbance and exercise. Methods Data were obtained from the MY-Health study, a community-based observational study of adults diagnosed with cancer. Patient-Reported Outcomes Measurement Information System® (PROMIS) measures (e.g., PROMIS Sleep) were administered, and participants self-reported demographics, comorbidities, cancer treatment, and exercise. Regression mixture and multiple regression models were used to evaluate the relationship between sleep disturbance and exercise cross-sectionally at an average of 10 months after diagnosis, and the change in sleep disturbance over a 7-month period, from approximately 10 to 17 months post-diagnosis. Results Patients whose exercise was categorized as likely at or above American College of Sports Medicine’s guidelines did not report statistically better sleep quality compared to patients who were classified as not active. However, retirement (B = − 2.4), anxiety (B = 0.21), and fatigue (B = 0.24) had statistically significant relationships with sleep disturbance (p < 0.05). Increase in exercise was not significantly associated with a decrease in sleep disturbance. No statistical heterogeneity was revealed in the relationship between sleep and exercise. Conclusions Further prospective research using an objective measure of exercise is warranted to confirm or refute the nature of the relationship between exercise and sleep disturbance in individuals diagnosed with CRC transitioning off first-line treatment

A global experiment on motivating social distancing during the COVID-19 pandemic

Finding communication strategies that effectively motivate social distancing continues to be a global public health priority during the COVID-19 pandemic. This cross-country, preregistered experiment (n = 25,718 from 89 countries) tested hypotheses concerning generalizable positive and negative outcomes of social distancing messages that promoted personal agency and reflective choices (i.e., an autonomy-supportive message) or were restrictive and shaming (i.e., a controlling message) compared with no message at all. Results partially supported experimental hypotheses in that the controlling message increased controlled motivation (a poorly internalized form of motivation relying on shame, guilt, and fear of social consequences) relative to no message. On the other hand, the autonomy-supportive message lowered feelings of defiance compared with the controlling message, but the controlling message did not differ from receiving no message at all. Unexpectedly, messages did not influence autonomous motivation (a highly internalized form of motivation relying on one’s core values) or behavioral intentions. Results supported hypothesized associations between people’s existing autonomous and controlled motivations and self-reported behavioral intentions to engage in social distancing. Controlled motivation was associated with more defiance and less long-term behavioral intention to engage in social distancing, whereas autonomous motivation was associated with less defiance and more short- and long-term intentions to social distance. Overall, this work highlights the potential harm of using shaming and pressuring language in public health communication, with implications for the current and future global health challenges

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

A global experiment on motivating social distancing during the COVID-19 pandemic

Finding communication strategies that effectively motivate social distancing continues to be a global public health priority during the COVID-19 pandemic. This cross-country, preregistered experiment (n = 25,718 from 89 countries) tested hypotheses concerning generalizable positive and negative outcomes of social distancing messages that promoted personal agency and reflective choices (i.e., an autonomy-supportive message) or were restrictive and shaming (i.e. a controlling message) compared to no message at all. Results partially supported experimental hypotheses in that the controlling message increased controlled motivation (a poorly-internalized form of motivation relying on shame, guilt, and fear of social consequences) relative to no message. On the other hand, the autonomy-supportive message lowered feelings of defiance compared to the controlling message, but the controlling message did not differ from receiving no message at all. Unexpectedly, messages did not influence autonomous motivation (a highly-internalized form of motivation relying on one’s core values) or behavioral intentions. Results supported hypothesized associations between people’s existing autonomous and controlled motivations and self-reported behavioral intentions to engage in social distancing: Controlled motivation was associated with more defiance and less long-term behavioral intentions to engage in social distancing, whereas autonomous motivation was associated with less defiance and more short- and long-term intentions to social distance. Overall, this work highlights the potential harm of using shaming and pressuring language in public health communication, with implications for the current and future global health challenges

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Prediction of cellular ATP generation from foods in the adult human : application to developing specialist weight-loss foods : a thesis presented in partial fulfilment of the requirements for the degree of Doctor of Philosophy in Nutritional Science at Massey University, Palmerston North, New Zealand

For the accurate prediction of the potential ‘available energy’ of a food at the cellular level (i.e. ATP generation from food) it is necessary to be able to predict both the quantity and location of uptake (upper-tract or colon) for each energy-yielding nutrient. The objective was to develop a valid model (‘Combined Model’) for predicting the (potential) ATP available to the body from absorbed nutrients across the total digestive tract. The model was intended for the adult human under conditions where energy intake ≤ energy expenditure and all absorbed nutrients are catabolised. The development of the model involved two parts: (i) the experimental development of a dual in vivo – in vitro digestibility assay (‘dual digestibility assay’) to predict human upper-tract nutrient digestibility, as modelled by the rat upper digestive tract, and colonic digestibility, as predicted by fermenting rat ileal digesta in an in vitro digestion system containing human faecal bacteria; and (ii) the development of a series of mathematical equations to predict the net ATP yielded during the post-absorptive catabolism of each absorbed nutrient at the cellular level. A strong correlation (r=0.953, P=0.047) was found between total tract organic matter digestibility (OMD), as predicted with the newly developed dual in vivo – in vitro digestibility assay and with that determined in a metabolic study with humans for four mixed diets ranging considerably in nutrient content. There were no statistically significant (P>0.05) differences for mean OMD between the predicted and determined values for any of the diets. The Combined Model (dual in vivo – in vitro digestibility assay + stoichiometric predictive equations) was applied to three meal replacement formulations and was successfully able to differentiate between the diets in terms of both energy digestibility and predicted ATP yields. When the energy content of each diet was compared to that of a baseline food (dextrin), some metabolisable energy (ME) models gave considerably different ratios compared to that predicted by the Combined Model. By way of example, for Diet C a ratio of 0.96 (Atwater and FDA models) was found ii versus 0.75 (Combined Model). Thus, the model has practical application for predicting dietary available energy content, particularly in the research and development of specialised weight-loss foods, where it may be more accurate than some current ME models. Uniquely, the Combined Model is able to define a food in terms of ATP content (mol ATP / g food) using recent estimates of cellular P/O ratios and therefore, directly relates dietary energy intake to the quantity and form (ATP) of energy ultimately delivered at the cellular level

Patient-Centered Outcomes Associated With a Novel Office-Based Opioid Treatment Program in a District Health Department: Mixed Methods Pilot Study

BackgroundGranville and Vance counties have some of the highest opioid-related death rates in North Carolina, and have significant unmet needs with regard to opioid treatment. Medication for opioid use disorder (MOUD) is the most effective evidence-based approach to address opioid use disorder. Despite demonstrated efficacy and substantial need, access to MOUD is still insufficient in many parts of the United States. In order to connect patients with needed MOUD services, the district health department, Granville Vance Public Health (GVPH), established an office-based opioid treatment (OBOT) program. ObjectiveIn this formative pilot study, we sought to describe patients’ goals and outcomes in a program delivered at a rural local health department using an integrated care approach. MethodsWe used a mixed methods concurrent nested research design. The primary method of investigation was one-on-one qualitative interviews with active OBOT patients (n=7) focused on patients’ goals and perceived impacts of the program. Trained interviewers followed a semistructured interview guide developed iteratively by the study team. The secondary method was a descriptive quantitative analysis (79 patients; 1478 visits over 2.5 years) of treatment retention and patient-reported outcomes (anxiety and depression). ResultsParticipants in the OBOT program were 39.6 years of age on average, and 25.3% (20/79) were uninsured. The average retention in the program was 18.4 months. The proportion of individuals in the program with moderate to severe depression (Patient Health Questionnaire-9 scores ≥10) decreased between program initiation (66%, 23/35) and at the most recent assessment (34%, 11/32). In qualitative interviews, participants credited the OBOT program for reducing or stopping the use of opioids and other substances (eg, marijuana, cocaine, and benzodiazepines). Many participants noted how the program helped them manage withdrawal symptoms and cravings, which helped them feel more in control of their use. Participants also attributed improvements in quality of life to the OBOT program, such as improved relationships with loved ones, improved mental and physical health, and improved financial stability. ConclusionsInitial data show promising patient outcomes for active GVPH OBOT participants, including reduction in opioid use and improvements in quality of life. As a pilot study, a limitation of this study is a lack of a comparison group. However, this formative project demonstrates promising patient-centered outcome improvements for GVPH OBOT participants