Predictors of Sustained Response to Functional Restoration in a Military Population.

INTRODUCTION: The purpose of this study was to determine if improvement in pain impact and functional performance following a functional restoration (FR) program was sustained up to 6 months posttreatment and to identify predictors of sustained improvement. MATERIALS AND METHODS: Secondary analysis of data collected during randomized clinical trial. Study population included 108 US active duty service members who completed an FR program, as well as 3- and/or 6-month follow-up assessments. Primary outcome measure was the NIH Research Task Force (pain) impact score (PIS). Secondary outcome was a composite functional performance measure of treadmill, lifting, and carrying tolerances. Variables analyzed to determine their predictive value included demographics; treatment hours; measures of pain intensity, function, mood, sleep, social satisfaction, pain catastrophizing, kinesiophobia, self-efficacy, pain acceptance, patient activation, functional performance, and neuropathic pain. RESULTS: Mean PIS and functional performance improved significantly immediately following FR, but after 6 months, only improvement in functional performance sustained. Responder analysis showed that 6 months after FR, 42% of participants reported improvement that exceeded the minimal clinically important difference in PIS or functional performance. Predictors of sustained PIS improvement included younger age, absence of neuropathic pain features, less self-rated disability, better baseline functional performance, and worse baseline PIS. Predictors of sustained functional performance improvement included more treatment hours, lower baseline pain catastrophizing, and lower baseline functional performance. CONCLUSIONS: This study supports the investment of treatment time in FR to yield sustained clinically meaningful improvement, as observed in over 40% of this study's military participants. Pretreatment predictors of sustained response included lower pain catastrophizing and absence of neuropathic pain. Further research is needed to determine if treatments that improve pain catastrophizing and neuropathic pain will result in sustained improvement in pain impact and functional performance following FR program participation.

Monitoring and responding to signals of suicidal ideation in pragmatic clinical trials: Lessons from the GRACE trial for Chronic Sickle Cell Disease Pain.

Sickle cell disease (SCD) is a hemoglobin disorder and the most common genetic disorder that affects 100,000 Americans and millions worldwide. Adults living with SCD have pain so severe that it often requires opioids to keep it in control. Depression is a major global public health concern associated with an increased risk in chronic medical disorders, including in adults living with sickle cell disease (SCD). A strong relationship exists between suicidal ideation, suicide attempts, and depression. Researchers enrolling adults living with SCD in pragmatic clinical trials are obligated to design their methods to deliberately monitor and respond to symptoms related to depression and suicidal ideation. This will offer increased protection for their participants and help clinical investigators meet their fiduciary duties. This article presents a review of this sociotechnical milieu that highlights, analyzes, and offers recommendations to address ethical considerations in the development of protocols, procedures, and monitoring activities related to suicidality in depressed patients in a pragmatic clinical trial.

Association between sleep variability and time in range of glucose levels in patients with type 1 diabetes: Cross-sectional study.

OBJECTIVE: Sleep and circadian disturbances emerge as novel factors influencing glycemic control in type 1 diabetes (T1D). We aimed to explore the associations among sleep, behavioral circadian parameters, self-care, and glycemic parameters in T1D. METHODS: Seventy-six non-shift-working adult T1D patients participated. Blinded 7-day continuous glucose monitoring (CGM) and hemoglobin A1C (A1C) were collected. Percentages of time-in-range (glucose levels 70-180 mg/dL) and glycemic variability (measured by the coefficient of variation [%CV]) were calculated from CGM. Sleep (duration and efficiency) was recorded using 7-day actigraphy. Variability (standard deviation) of midsleep time was used to represent sleep variability. Nonparametric behavioral circadian variables were derived from actigraphy activity recordings. Self-care was measured by diabetes self-management questionnaire-revised. Multiple regression analyses were performed to identify independent predictors of glycemic parameters. RESULTS: Median (interquartile range) age was 34.0 (27.2, 43.1) years, 48 (63.2%) were female, and median (interquartile range) A1C was 6.8% (6.2, 7.4). Sleep duration, efficiency, and nonparametric behavioral circadian variables were not associated with glycemic parameters. After adjusting for age, sex, insulin delivery mode/CGM use, and ethnicity, each hour increase in sleep variability was associated with 9.64% less time-in-range (B = -9.64, 95% confidence interval [-16.29, -2.99], p ≤ .001). A higher diabetes self-management questionnaire score was an independent predictor of lower A1C (B = -0.18, 95% confidence interval [-0.32, -0.04]). CONCLUSION: Greater sleep timing variability is independently associated with less time spent in the desirable glucose range in this T1D cohort. Reducing sleep timing variability could potentially lead to improved metabolic control and should be explored in future research. DATA AVAILABILITY STATEMENT: Data are available upon a reasonable request to the corresponding author.

Associations in Cigarette Smoking and Health Conditions by Race/Ethnicity Among a Diverse Sample of Patients Receiving Treatment in a Federally Qualified Health Care Setting in Chicago.

Purpose: To examine the association of cigarette use and smoking-related health conditions by race/ethnicity among diverse and low-income patients at a federally qualified health center (FQHC). Methods: Demographics, smoking status, health conditions, death, and health service use were extracted from electronic medical data for patients seen between September 1, 2018, and August 31, 2020 (n=51,670). Smoking categories included everyday/heavy smoker, someday/light smoker, former smoker, or never smoker. Results: Current and former smoking rates were 20.1% and 15.2%, respectively. Males, Black, White, non-partnered, older, and Medicaid/Medicare patients were more likely to smoke. Compared with never smokers, former and heavy smokers had higher odds for all health conditions except respiratory failure, and light smokers had higher odds of asthma, chronic obstructive pulmonary disease, emphysema, and peripheral vascular disease. All smoking categories had more emergency department visits and hospitalizations than never smokers. The associations between smoking status and health conditions differed by race/ethnicity. White patients who smoked had a greater increase in odds of stroke and other cardiovascular diseases compared with Hispanic and Black patients. Black patients who smoked had a greater increase in odds of emphysema and respiratory failure compared with Hispanic patients. Black and Hispanic patients who smoked had a greater increase in emergency care use compared with White patients. Conclusion: Smoking was associated with disease burden and emergency care and differed by race/ethnicity. Health Equity Implications: Resources to document smoking status and offer cessation services should be increased in FQHCs to promote health equity for lower income populations.

A Systematic Review and Meta-analysis of the Initial Literature Regarding COVID-19 Symptoms in Children in the United States.

INTRODUCTION: COVID-19 symptom presentation among adults is mostly understood. However, understanding COVID-19 symptom presentation in children lags. METHOD: A literature search was conducted in three electronic databases. Twenty-three initial publications addressing COVID-19 symptom presentation among hospitalized children in the United States met the criteria for review and meta-analysis. RESULTS: Fever, the most common symptom, was present in nearly all cases. Gastrointestinal, respiratory, oral symptoms, and rash occurred in over half of the cases. Disease severity assessment showed that comorbidities were present in one-third of patients; intensive care was needed for half of the patients, and supplemental oxygen and mechanical ventilation were needed by 13.3% and 7.1%, respectively. DISCUSSION: The magnitude and significance of COVID-19 symptoms in children compared with those in adults and three common childhood viral illnesses: influenza, respiratory syncytial virus, and gastroenteritis, are discussed. Important clinical differences were found that may help clinicians distinguish COVID-19 from other illnesses.

Hybrid effectiveness-implementation trial of guided relaxation and acupuncture for chronic sickle cell disease pain (GRACE): A protocol.

Background: People with sickle cell disease frequently use complementary and integrative therapies to cope with their pain, yet few studies have evaluated their effectiveness. The 3-arm, 3-site pragmatic Hybrid Effectiveness-implementation Trial of Guided Relaxation and Acupuncture for Chronic Sickle Cell Disease Pain (GRACE) has 3 priorities: (1) evaluate guided relaxation and acupuncture to improve pain control; (2) determine the most appropriate and effective treatment sequence for any given patient based on their unique characteristics; and (3) describe the processes and structures required to implement guided relaxation and acupuncture within health care systems. Methods: Participants (N = 366) are being recruited and randomized 1:1:1 to one of 2 intervention groups or usual care. The acupuncture intervention group receives 10 sessions over approximately 5 weeks. The guided relaxation intervention group receives access to video sessions ranging from 2 to 20 min each viewed daily over 5 weeks. The usual care group receives the standard of clinical care for sickle cell disease. Participants are re-randomized at 6 weeks depending on their pain impact score. Assessments occur at 6 weeks, 12 weeks, and 24 weeks. The primary outcome is the change in pain impact score and secondary measures include opioid use, anxiety, depression, sleep, pain catastrophizing, substance use, global impression of change, constipation, and hospitalizations. The GRACE study uses the Consolidated Framework for Implementation Research to plan, execute, and evaluate the associated implementation processes. Conclusion: The results from GRACE will represent a critical step toward improving management of pain affecting patients with sickle cell disease.ClinicalTrials.gov Identifier: NCT04906447.

Sleep-Opt-In: A Randomized Controlled Pilot Study to Improve Sleep and Glycemic Variability in Adults With Type 1 Diabetes.

PURPOSE: The purpose of this study was to evaluate the feasibility and acceptability of a technology-assisted behavioral sleep intervention (Sleep-Opt-In) and to examine the effects of Sleep-Opt-In on sleep duration and regularity, glucose indices, and patient-reported outcomes. Short sleep duration and irregular sleep schedules are associated with reduced glycemic control and greater glycemic variability. METHODS: A randomized controlled parallel-arm pilot study was employed. Adults with type 1 diabetes (n = 14) were recruited from the Midwest and randomized 3:2 to the sleep-optimization (Sleep-Opt-In) or Healthy Living attention control group. Sleep-Opt-In was an 8-week, remotely delivered intervention consisting of digital lessons, sleep tracker, and weekly coaching phone calls by a trained sleep coach. Assessments of sleep (actigraphy), glucose (A1C, continuous glucose monitoring), and patient-reported outcomes (questionnaires for daytime sleepiness, fatigue, diabetes distress, and depressive mood) were completed at baseline and at completion of the intervention. RESULTS: Sleep-Opt-In was feasible and acceptable. Those in Sleep-Opt-In with objectively confirmed short or irregular sleep demonstrated an improvement in sleep regularity (25 minutes), reduced glycemic variability (3.2%), and improved time in range (6.9%) compared to the Healthy Living attention control group. Patient-reported outcomes improved only for the Sleep-Opt-In group. Fatigue and depressive mood improved compared to the control. CONCLUSIONS: Sleep-Opt-In is feasible, acceptable, and promising for further evaluation as a means to improve sleep duration or regularity in the population of people with type 1 diabetes.

Pattern of Cumulative Treatment Hours on Pain Impact and PROMIS Outcomes.

INTRODUCTION: Participation in interdisciplinary treatments is associated with improvement in pain intensity, physical function, and additional pain-related outcome domains. However, the effect of cumulative treatment hours on outcomes remains unknown among military patients. The present analysis examined the relationship between cumulative interdisciplinary treatment hours and pain management outcomes at a single interdisciplinary pain management center (IPMC). MATERIALS AND METHODS: This is a retrospective observational study of data previously collected as standard of care at the Madigan Army Medical Center, approved by the Institutional Review Board. We included patients who received treatment at the IPMC and completed at least two self-report assessment batteries: one at baseline and at least one between 90 and 180 days after baseline (n = 882). The primary outcome was pain impact. Secondary outcomes included fatigue, depression, anxiety, and sleep-related impairment. RESULTS: Generalized additive models indicated that cumulative treatment hours were significantly associated with improvement in pain impact, fatigue, and depression. Patients who had higher baseline pain impact, who had mild or no depressive symptoms, and who were >40 years of age had greater improvements in pain impact following treatment, relative to those with lower pain impact, moderate-to-severe depressive symptoms, and were 40 years of age or younger, respectively. Additional research is needed to elucidate the effect of different therapies and additional patient factors in understanding the "therapeutic dose" of interdisciplinary pain management. CONCLUSIONS: A higher number of cumulative treatment hours was associated with improvement of pain impact, fatigue, and depression among military personnel receiving interdisciplinary pain treatment. At least 30 hours of sustained interdisciplinary treatment appears to be the threshold for improvement in pain impact and related outcomes.

Women's Experience of Living with Vulvodynia Pain: Why They Participated in a Randomized Controlled Trial of Acupuncture.

Introduction: Vulvodynia is vulvar pain lasting at least 3-months without clear identifiable cause that may have other associated factors. The aim, to explore motivations of women participating in a double-blind randomized controlled trial of acupuncture for vulvodynia. Methods: Responses to the question: "Tell me about why you decided to participate in this study" were analyzed using conceptual content analysis to identify patterns in motivation for study participation. Results: Four patterns emerged: 1) desire to address uncontrolled pain, 2) desire for understanding, 3) wish to contribute to knowledge generation, and 4) need to remove cost barriers. Conclusion: Motivations indicate vulvodynia-specific aspects of acceptability of acupuncture. Clinical Trial Registration: NCT03364127.

How deep is the cut? The influence of daily microaggressions on bisexual women's health.

Bisexual women experience disproportionately poorer health outcomes in comparison to lesbian and gay groups, and the general population, including inequities related to mental and physical health. Although bisexual-specific health inequities are increasingly well-documented, research examining putative causes of such inequities, as well as research that accounts for differences within bisexual populations - particularly among racial minorities- remains limited. To address these gaps, this paper reports findings from the Women's Daily Experiences Study (WoDES), a multi-method study that explored the relationship between microaggressions and health outcomes among racially/ethnically diverse cisgender, bisexual women in Chicago. Data from 28-day daily e-diaries (N = 2,104 observations; 99 participants, 57% women of color) were analyzed using multilevel modeling to (1) measure the frequency of microaggressions among bisexual women; (2) examine the influence of sexual orientation, racial, and gender microaggressions on mental and physical health; and (3) investigate how race influences relationships between microaggressions and health. Participants reported an average of 8.1 microaggressions in the previous 28 days, and at least one microaggression was reported for more than 42% of days (n = 802). Microaggressions of any type were associated with increased same-day negative affect and somatic complaints. Latina bisexual women experienced worse health outcomes in comparison to Black bisexual women. This study demonstrated the detrimental impact of microaggressions on the health of bisexual women and highlights the critical need for strategies on broader structural changes that could improve the health and well-being of bisexual women.

Protocol for double-blind RCT of acupuncture for vulvodynia.

Background: Vulvodynia, vulvar pain of unknown origin lasting at least 3 months, affects 7% of American women. Dyspareunia, its frequent companion, renders sexual intercourse virtually impossible. Although few therapies are efficacious and rapid pain relief is rarely possible, there have been no sham/placebo-controlled studies of acupuncture for vulvodynia. Aims are to: 1) determine efficacy of acupuncture for vulvodynia, 2) explore duration of the acupuncture effect. Methods: In a pretest/posttest randomized controlled, double-blind (practitioner-patient) efficacy trial of a standardized acupuncture protocol, we will randomize 80 participants 1:1 to either penetrating needle or skin-touch placebo needle groups. Both types of needles are designed to blind both the acupuncturist and participant. Participants with vulvodynia will insert and remove a tampon as a standardized stimulus and complete primary measures of vulvar pain (pain intensity) and secondary measures of dyspareunia (Female Sexual Function Index, FSFI dyspareunia subscale score) and sexual function (FSFI total score) pretreatment, after the 10th acupuncture session, and pain measures weekly until return to pretest levels. Upon study completion control group participants will be offered 10 free real acupuncture sessions. Discussion: This is the first multi-needle multi-session RCT using double-blind acupuncture needles as a reliable sham. We hypothesize that controlling for baseline, at posttest there will be statistically significant less vulvar pain and dyspareunia and more sexual function over five weeks in the penetrating needle group compared to the skin touch placebo group. Conclusion: This study is responsive to the need for efficacious pain management for women with vulvodynia.ClinicalTrials.gov Identifier: NCT03364127.

Use of a treadmill, lift, and carry battery as a composite functional performance test: analysis of data from a pragmatic randomized controlled trial in a military population participating in a functional restoration program.

BACKGROUND: The treadmill, lift, and carry (TLC) battery is a composite functional performance test created to measure the effectiveness of a functional restoration (FR) program in a military population. PURPOSE: To determine the validity, reliability, and minimal clinically important differences (MCIDs) of the individual tests and the composite TLC battery. METHODS: We assessed the validity by mean differences, effect sizes, and standardized response means pre- and post-FR; and by correlations between the TLC battery and other established measures. We assessed reliability by correlating pre- and post-FR scores. We used principal component analysis (PCA) to create a composite measure. We determined MCIDs via distribution methods and receiver operator curve analysis. RESULTS: There were significant (p < .001) mean changes and large effect sizes (0.6-0.8) pre- to post-FR. Pre- and posttest Spearman's correlations ranged from 0.5 to 0.6. Spearman's correlations between TLC battery scores and other measures were small (± 0.3-0.4) and significant (p < .001). PCA supported use of a single-component composite. MCIDs were treadmill time: 3 minutes; metabolic equivalent of task: 1.5 units; floor-to-waist lift: 15 lbs; waist-to-shoulder lift: 10 lbs; 40-foot carry: 10 lbs; and composite score: 6 units. CONCLUSION: This secondary data analysis provides preliminary support for the validity and reliability of the TLC battery for use in military populations.

Sleep optimization to improve glycemic control in adults with type 1 diabetes: study protocol for a randomized controlled parallel intervention trial.

BACKGROUND: Despite improvements in treatment regimens and technology, less than 20% of adults with type 1 diabetes (T1D) achieve glycemic targets. Sleep is increasingly recognized as a potentially modifiable target for improving glycemic control. Diabetes distress, poor self-management behaviors, and reduced quality of life have also been linked to sleep variability and insufficient sleep duration. A significant gap of knowledge exists regarding interventions to improve sleep and the effects of sleep optimization on glycemic control in T1D. The purpose of this study is to determine the efficacy of a T1D-specific sleep optimization intervention (Sleep-Opt) on the primary outcomes of sleep variability, sleep duration, and glycemic control (A1C); other glycemic parameters (glycemic variability, time-in-range [TIR]); diabetes distress; self-management behaviors; quality of life; and other patient-reported outcomes in adults with T1D and habitual increased sleep variability or short sleep duration. METHODS: A randomized controlled parallel-arm study will be employed in 120 adults (aged 18 to 65 years) with T1D. Participants will be screened for habitual sleep variability (> 1 h/week) or insufficient sleep duration (< 6.5 h per night). Eligible subjects will be randomized to the Sleep-Opt intervention group or healthy living attention control group for 12 weeks. A 1-week run-in period is planned, with baseline measures of sleep by actigraphy (sleep variability and duration), glycemia (A1C and related glycemic measures: glycemic variability and TIR using continuous glucose monitoring), and other secondary outcomes: diabetes distress, self-management behaviors, quality of life, and additional patient-reported outcomes. Sleep-Opt is a technology-assisted behavioral sleep intervention that we recently developed that leverages the rapidly increasing public interest in sleep tracking. Our behavioral intervention employs four elements: a wearable sleep tracker, didactic content, an interactive smartphone application, and brief telephone counseling. The attention control group will participate in a healthy living information program. Baseline measures will be repeated at midpoint, program completion, and post-program (weeks 6, 12, and 24, respectively) to determine differences between the two groups and sustainability of the intervention. DISCUSSION: A better understanding of strategies to improve sleep in persons with T1D has the potential to be an important component of diabetes. TRIAL REGISTRATION: Clinical Trial Registration: NCT04506151 .

Preliminary Evaluation of a Citizen Scientist Educational Curriculum Aimed at Engaging Black Men in Lung Cancer Early Detection Screening.

This article describes an educational program to engage African American men as citizen scientists (CSs) and future research partners in a lung cancer screening project. We provide an overview of the curriculum used, the structure and format of the educational sessions, and associated educational outcomes. Furthermore, we describe lessons learned in the engagement of African American men as CS in community-based lung-health equity research. The CS educational program included five group-based sessions delivered through zoom. The educational curriculum was adapted from the University of Florida Citizen Scientist program and tailored to address lung health and the contextual experiences of African American men. Each session lasted 90 minutes. Pre- and post-test measures were collected to examine changes in knowledge, comfort, health literacy, research interests, and medical mistrust. Eight African American men completed the CS educational program. Attendance rates were high for each session (100%). Seven participants completed additional human subject research certification. Improvements were observed from pre- to post-test in participants' level of knowledge, comfort, and health literacy but not medical mistrust. CS reported the most interest in participating in research aimed to identify important community strengths and problems. Study findings suggest that it was feasible to deliver an online citizen scientist educational program designed to prepare participants to serve as partners in a lung cancer screening intervention for African American men. Results suggest the educational program has the potential to improve key outcomes including completion of regulatory training and increased research-related knowledge, comfort, and health literacy.

Use of Complementary and Integrative Health Therapies Before Intensive Functional Restoration in Active Duty Service Members with Chronic Pain.

OBJECTIVE: Psychosocial factors are known to predict chronic pain, and the use of complementary and integrative health (CIH) therapies to address pain is emerging among the military population. However, conflicting results on pain outcomes warrant additional research. This study aimed to 1) evaluate the benefit of adding a CIH pain management program to standard rehabilitative care (SRC), as compared with SRC alone, as a precursor to an intensive functional restoration (FR) program; 2) identify factors that predict improvement in pain outcomes after treatment; and 3) determine the proportion of participants who experience a clinically meaningful response. DESIGN: Pragmatic randomized controlled clinical trial. Participants were randomized to a 3-week course of either SRC alone or SRC+CIH (stage 1), followed by a 3- to 6-week course of FR (stage 2). SUBJECTS: Active duty service members with chronic pain. METHODS: Participants completed either SRC alone or SRC+CIH (stage 1), followed by a course of FR (stage 2). Patient-reported and provider-determined outcomes were collected at baseline, after stage 1, and after stage 2. A covariance pattern model with an unstructured residual covariance matrix was used to compare treatment arms while accounting for dependency due to repeated measurements. RESULTS: A total of 210 service members participated. Most were in the Army (82%) and were male (84%). Participants randomized to the SRC+CIH intervention had greater improvement in the pain impact score than did those in the SRC-alone group. Predictors of outcomes were baseline impact score, anger, depression, and educational status. CONCLUSIONS: This study found that military service members with the highest pain impact benefit the most from interdisciplinary pain care.

Womb to womb: Maternal litter size and birth weight but not adult characteristics predict early neonatal death of offspring in the common marmoset monkey.

A singular focus on maternal health at the time of a pregnancy leaves much about perinatal mortality unexplained, especially when there is growing evidence for maternal early life effects. Further, lumping stillbirth and early neonatal death into a single category of perinatal mortality may obscure different causes and thus different avenues of screening and prevention. The common marmoset monkey (Callithrix jacchus), a litter-bearing nonhuman primate, is an ideal species in which to study the independent effects of a mother's early life and adult phenotypes on pregnancy outcomes. We tested two hypotheses in 59 marmoset pregnancies at the Southwest National Primate Research Center and the Barshop Institute for Longevity and Aging Studies. We explored 1) whether pregnancy outcomes were predicted independently by maternal adult weight versus maternal litter size and birth weight, and 2) whether stillbirth and early neonatal death were differentially predicted by maternal variables. No maternal characteristics predicted stillbirth and no maternal adult characteristics predicted early neonatal death. In univariate Poisson models, triplet-born females had a significantly increased rate of early neonatal death (IRR[se] = 3.00[1.29], p = 0.011), while higher birth weight females had a decreased rate (IRR[se] = 0.89[0.05], p = 0.039). In multivariate Poisson models, maternal litter size remained an independent predictor, explaining 13% of the variance in early neonatal death. We found that the later in the first week those neonates died, the more weight they lost. Together these findings suggest that triplet-born and low birth weight females have distinct developmental trajectories underlying greater rates of infant loss, losses that we suggest may be attributable to developmental disruption of infant feeding and carrying. Our findings of early life contributions to adult pregnancy outcomes in the common marmoset disrupt mother-blaming narratives of pregnancy outcomes in humans. These narratives hold that the pregnant person is solely responsible for pregnancy outcomes and the health of their children, independent of socioecological factors, a moralistic framing that has shaped clinical pregnancy management. It is necessary to differentiate temporal trajectories and causes of perinatal loss and view them as embedded in external processes to develop screening, diagnostic, and treatment tools that consider the full arc of a mother's lived experience, from womb to womb and beyond.

Lesioning of the pedunculopontine nucleus reduces rapid eye movement sleep, but does not alter cardiorespiratory activities during sleep, under hypoxic conditions in rats.

To determine how partial lesioning of the pedunculopontine nucleus (PPT) affects sleep, breathing, and blood pressure in rats, ibotenic acid (IBO) was injected bilaterally into the PPT. Sham-injected (saline) and IBO-lesioned rats were first studied under normoxic conditions (40 recordings were obtained from 15 rats, with each recording lasting for 6 daytime hours). Rats were then exposed to intermittent hypoxia for 4 ± 2 days (51 recordings from 12 rats, each lasting 6 daytime hours). The intermittent hypoxia protocol involved an oxygen decline lasting 35 s (to a nadir of 10 %) followed by a 50 s increase to normoxia. The IBO caused an estimated 53 % reduction in PPT neurons. When normoxic, IBO-lesioned rats had remarkedly normal sleep architecture, respiratory rates, and mean arterial pressure. The exposure to intermittent hypoxia evoked tachypnea in both the IBO-lesioned and sham-injected rats. When intermittently hypoxic, IBO-lesioned rats demonstrated a significant reduction in the duration of rapid eye movement (REM) sleep. We conclude that partial lesions of the PPT do not disrupt cardiorespiratory activities, but a reduction in PPT neurons impairs the ability to sustain REM sleep under hypoxic conditions.

Double-blinding of an acupuncture randomized controlled trial optimized with clinical translational science award resources.

BACKGROUND: Clinical trial articles often lack detailed descriptions of the methods used to randomize participants, conceal allocation, and blind subjects and investigators to group assignment. We describe our systematic approach to implement and measure blinding success in a double-blind phase 2 randomized controlled trial testing the efficacy of acupuncture for the treatment of vulvodynia. METHODS: Randomization stratified by vulvodynia subtype is managed by Research Electronic Data Capture software's randomization module adapted to achieve complete masking of group allocation. Subject and acupuncturist blinding assessments are conducted multiple times to identify possible correlates of unblinding. RESULTS: At present, 48 subjects have been randomized and completed the protocol resulting in 87 subject and 206 acupuncturist blinding assessments. DISCUSSION: Our approach to blinding and blinding assessment has the potential to improve our understanding of unblinding over time in the presence of possible clinical improvement.

Sleep fragmentation increases blood pressure and is associated with alterations in the gut microbiome and fecal metabolome in rats.

The gut microbiota, via the production of metabolites entering the circulation, plays a role in blood pressure regulation. Blood pressure is also affected by the characteristics of sleep. To date, no studies have examined relationships among the gut microbiota/metabolites, blood pressure, and sleep. We hypothesized that fragmented sleep is associated with elevated mean arterial pressure, an altered and dysbiotic gut microbial community, and changes in fecal metabolites. In our model system, rats were randomized to 8 h of sleep fragmentation during the rest phase (light phase) or were undisturbed (controls) for 28 consecutive days. Rats underwent sleep and blood pressure recordings, and fecal samples were analyzed during: baseline (days -4 to -1), early sleep fragmentation (days 0-3), midsleep fragmentation (days 6-13), late sleep fragmentation (days 20-27), and recovery/rest (days 28-34). Less sleep per hour during the sleep fragmentation period was associated with increased mean arterial pressure. Analyses of gut microbial communities and metabolites revealed that putative short chain fatty acid-producing bacteria were differentially abundant between control and intervention animals during mid-/late sleep fragmentation and recovery. Midsleep fragmentation was also characterized by lower alpha diversity, lower Firmicutes:Bacteroidetes ratio, and higher Proteobacteria in intervention rats. Elevated putative succinate-producing bacteria and acetate-producing bacteria were associated with lower and higher mean arterial pressure, respectively, and untargeted metabolomics analysis demonstrates that certain fecal metabolites are significantly correlated with blood pressure. These data reveal associations between sleep fragmentation, mean arterial pressure, and the gut microbiome/fecal metabolome and provide insight to links between disrupted sleep and cardiovascular pathology.

Global assessment instrument for quality of nursing doctoral education with a research focus: Validity and reliability study.

OBJECTIVES: This study was designed to assess the content and construct validity and reliability of the Quality of Nursing Doctoral Education (QNDE) instrument for nursing doctoral programmes with a research focus. DESIGN: A cross-sectional, survey study. SETTINGS: Using Qualtrics survey, the research team sent emails to potential participants providing a link to the study and the QNDE instrument. PARTICIPANTS: A total of 234 faculty and doctoral students participated: 17 faculty from 14 countries in the first stage; 111 faculty and 106 doctoral students from 20 countries in the second stage. METHODS: The content validity, internal consistency reliability, and construct validity of the four domains (program, faculty, resources, and evaluation) of the QNDE were examined in two stages. Data were collected from purposive samples of faculty and students between June 2018 and March 2019. Confirmatory factor analysis was conducted in ordinal scale using robust weighted least square mean and variance (WLSMV) adjusted estimator in MPlus 8. RESULTS: Content validity of the items in the four domains was accepted when the item showed content validity (I-CVI > 0.78). Internal consistency reliability in four domains was computed using Cronbach's alpha, α = 0.88 to 0.97. Construct validity of the QNDE was established by confirmatory factor analysis based on model fit statistics. Factor loading coefficients for all items in each domain were statistically significant (>0.5; p < .001). CONCLUSIONS: Participation of 234 faculty and doctoral students from 20 countries on four continents confirmed content validity, internal consistency reliability, and construct validity of the QNDE instrument. These findings support the credibility of this revised QNDE instrument for assessing the quality of nursing doctoral education with a research focus. This is a significant step forward in enhancing the capability for evaluating doctoral programmes.