Adapting MultiPLe behavior Interventions that eFfectively Improve (AMPLIFI) cancer survivor health: program project protocols for remote lifestyle intervention and assessment in 3 inter-related randomized controlled trials among survivors of obesity-related cancers.

BACKGROUND: Scalable, multiple behavior change interventions are needed to address poor diet, inactivity, and excess adiposity among the rising number of cancer survivors. Efficacy-tested diet (RENEW) and exercise (BEAT Cancer) programs were adapted for web delivery among middle-aged and older cancer survivors for the AMPLIFI study, a National Cancer Institute-funded, multi-site, program project. METHODS: Throughout the continental U.S., survivors of several obesity-related cancers are being recruited for three interconnected randomized controlled trials (RCTs). Projects 1 and 2 test 6-month diet or exercise interventions versus a wait-list control condition. Upon completion of the 6-month study period, the intervention participants receive the next behavior change sequence (i.e., diet receives exercise, exercise receives diet) and the wait-list control arm initiates a 12-month combined diet and exercise intervention. Project 3 tests the efficacy of the sequential versus simultaneous interventions. Assessments occur at baseline and semi-annually for up to 2-years and include: body mass index, health behaviors (diet quality, accelerometry-assessed physical activity/sleep), waist circumference, D3 creatine-assessed muscle mass, physical performance, potential mediators/moderators of treatment efficacy, biomarkers of inflammation and metabolic regulation, health care utilization, cost, and overall health. Four shared resources support AMPLIFI RCTs: 1) Administrative; 2) Adaptation, Dissemination and Implementation; 3) Recruitment and Retention; and 4) Assessment and Analysis. DISCUSSION: Representing a new generation of RCTs, AMPLIFI will exclusively use remote technologies to recruit, intervene and assess the efficacy of the newly-adapted, web-based diet and exercise interventions and determine whether sequential or combined delivery works best for at-risk (older, rural, racial minority) cancer survivors. TRIAL REGISTRATION: ClinicalTrials.gov , NCT04000880 . Registered 27 June 2019.

A Web-based Lifestyle Intervention for Cancer Survivors: Feasibility and Acceptability of SurvivorSHINE.

Assess the feasibility, acceptability, and preliminary efficacy of a healthy lifestyle website, SurvivorSHINE ( www.survivorshine.org ), for cancer survivors using a mixed-methods approach. Formative research included a comprehensive literature review and four focus groups on website preferences with diagnosis-diverse cancer survivors (N = 17). Their feedback informed a web adaptation of a telephone counseling and mailed-print lifestyle intervention previously found effective for cancer survivors. The resulting web-based intervention was examined in a 3-week, single-arm trial among 41 cancer survivors. Assessments of physical activity, diet, body weight, and knowledge related to exercise and diet guidelines for cancer survivors occurred at baseline and 3 weeks later, along with exit interviews. Themes from focus groups indicated cancer survivors' desire for easy-to-use, interactive web-based platforms to access credible diet and exercise information. The study sample was recruited within 12 months, and study retention was high (85.4%). Participants showed significant pre- to post-test improvements in diet and exercise knowledge (t = 5.31, p < .0001) and physical activity (t = 2.40, p = .02). Improvements in body weight and some dietary components (red meat, alcohol) were observed, but did not reach statistical significance. Results support the feasibility and acceptability of SurvivorSHINE. The significant increases in healthy lifestyle knowledge and physical activity found in the current study are promising, but a larger, randomized-controlled trial is needed to determine efficacy.

Science dialogue mapping of knowledge and knowledge gaps related to the effects of dairy intake on human cardiovascular health and disease.

Dairy has been described as everything from a superfood to a poison; yet, arguments, assumptions, and data justifying these labels are not always clear. We used an issue-based information system, "dialogue mapping™," to summarize scientific points of a live panel discussion on the putative effects of dairy on cardiovascular diseases (CVD) from a day-long session among experts in nutrition and CVD. Dialogue mapping captures relations among ideas to explicitly, logically, and visually connect issues/questions, ideas, pro/con arguments, and agreements, even if discussed at different times. Experts discussed two propositions: for CVD risk, consumption of full-fat dairy products 1) should be minimized, in part because of their saturated fat content, or 2) need not be minimized, despite their saturated fat content. The panel discussed the dairy-CVD relation through blood lipids, diabetes, obesity, energy balance, blood pressure, dairy bioactives, biobehavioral components, and other putative causal pathways. Associations and effects reported in the literature have varied by fat content of dairy elements considered, study design, intake methods, and biomarker versus disease outcomes. Two conceptual topics emerged from the discussion: 1) individual variability: whether recommendations should be targeted only to those at high CVD risk; 2) quality of evidence: whether data on dairy-CVD relations are strong enough for reliable conclusions-positive, negative, or null. Future procedural improvements for science dialog mapping include using singular rather than competing propositions for discussion.

Geospatial analysis of Mediterranean diet adherence in the United States.

OBJECTIVE: The current study aims to describe the Mediterranean diet (MD) adherence across the US regions, and explore the predictive factors of MD adherence among US adults. DESIGN: Cross-sectional secondary data analysis. MD adherence score (0-9) was calculated using the Block 98 FFQ. Hot spot analysis was conducted to describe the geospatial distribution of MD adherence across the US regions. Logistic regression explored predictors of MD adherence. SETTING: Nationwide community-dwelling residency in the USA. PARTICIPANTS: Adults aged ≥45 years (n 20 897) who participated in the REasons for Geographic and Racial Differences in Stroke study and completed baseline assessment during January 2003 and October 2007. RESULTS: The mean of MD adherence score was 4·36 (sd 1·70), and 46·5 % of the sample had high MD adherence (score 5-9). Higher MD adherence clusters were primarily located in the western and northeastern coastal areas of the USA, whereas lower MD adherence clusters were majorly observed in south and east-north-central regions. Being older, black, not a current smoker, having a college degree or above, an annual household income ≥ $US 75K, exercising ≥4 times/week and watching TV/video <4 h/d were each associated with higher odds of high MD adherence. CONCLUSIONS: There were significant geospatial and population disparities in MD adherence across the US regions. Future studies are needed to explore the causes of MD adherence disparities and develop effective interventions for MD promotion in the USA.

Dietary R, S-1,3-butanediol diacetoacetate reduces body weight and adiposity in obese mice fed a high-fat diet.

The dietary R-3-hydroxybutyrate- R-1,3-butanediol monoester increases resting energy expenditure (REE) and markers of brown and white adipose thermogenesis in lean mice. The purpose of this investigation was to determine whether the ketone ester, R, S-1,3-butanediol diacetoacetate (BD-AcAc2), increases energy expenditure and markers of adipose tissue thermogenesis in the context of high-fat diet (HFD)-induced obesity. Thirty-five-week-old male C57BL/6J mice were placed on an ad libitum HFD (45% kcal) for 10 wk. The mice were then randomized to 1 of 3 groups ( n = 10 per group) for an additional 12 wk: 1) control (Con), continuous HFD, 2) pair-fed (PF) to ketone ester (KE); and 3) KE: HFD+30% energy from BD-AcAc2. Mean energy intake throughout the study was ∼26% lower in the KE compared to the Con group (8.2 ± 0.5 vs. 11.2 ± 0.7 kcal/d; P < 0.05). Final body weight (26.8 ± 3.6 vs. 34.9 ± 4.8 g; P < 0.001) and fat mass (5.2 ± 1.2 vs. 11.3 ± 4.5 g; P < 0.001) of the KE group was significantly lower than PF, despite being matched for energy provisions. Differences in body weight and adiposity were accompanied by higher REE and total energy expenditure in the KE group compared to PF after adjustment for lean body mass and fat-mass ( P = 0.001 and 0.007, respectively). Coupled or uncoupled mitochondrial respiratory rates in skeletal muscle were not different among groups, but markers of mitochondrial uncoupling and thermogenesis (uncoupling protein-1, deiodinase-2, and peroxisome proliferator-activated receptor γ coactivator-1α) were higher in interscapular brown adipose tissue (BAT) of mice receiving the KE diet. The absence of mitochondrial uncoupling in skeletal muscle and increased markers of mitochondrial uncoupling in BAT suggest that BD-AcAc2 initiates a transcriptional signature consistent with BAT thermogenesis in the context of HFD-induced obesity.-Davis, R. A. H., Deemer, S. E., Bergeron, J. M., Little, J. T., Warren, J. L., Fisher, G., Smith, D. L., Jr., Fontaine, K. R., Dickinson, S. L., Allison, D. B., Plaisance, E. P. Dietary R, S-1,3-butanediol diacetoacetate reduces body weight and adiposity in obese mice fed a high-fat diet.

A Ketogenic Diet Is Acceptable in Women with Ovarian and Endometrial Cancer and Has No Adverse Effects on Blood Lipids: A Randomized, Controlled Trial.

Ketogenic diets (KDs) are emerging as effective therapies for several chronic diseases, including cancer. However, concerns regarding safety and adherence may prevent clinicians from prescribing KDs. We hypothesized that a KD does not negatively affect blood lipid profile compared to a lower-fat diet in ovarian and endometrial cancer patients, and that KD subjects would demonstrate acceptable adherence. Subjects were randomized to either a KD (70% fat, 25% protein, 5% carbohydrate), or the American Cancer Society diet (ACS; high-fiber and lower-fat). Blood lipids and ketones were measured at baseline and after 12 weeks of the assigned intervention. Adherence measures included urinary ketones in the KD and 4 days' diet records. Diet records were also examined to identify general patterns of consumption. Differences between the diets on blood lipids and dietary intake were assessed with Analysis of covariance and independent t-tests. Correlation analyses were used to estimate associations between dietary intake and serum analytes. At 12 weeks, there were no significant differences between diet groups in blood lipids, after adjusting for baseline values and weight loss. Adherence among KD subjects ranged from 57% to 80%. These findings suggest that KDs may be a safe and achievable component of treatment for some cancer patients.

Role of membrane compartment occupied by Can1 (MCC) and eisosome subdomains in plant pathogenicity of the necrotrophic fungus Alternaria brassicicola.

BACKGROUND: MCC/eisosomes are membrane microdomains that have been proposed to participate in the plasma membrane function in particular by regulating the homeostasis of lipids, promoting the recruitment of specific proteins and acting as provider of membrane reservoirs. RESULTS: Here we showed that several potential MCC/eisosomal protein encoding genes in the necrotrophic fungus A. brassicicola were overexpressed when germinated spores were exposed to antimicrobial defence compounds, osmotic and hydric stresses, which are major constraints encountered by the fungus during the plant colonization process. Mutants deficient for key MCC/eisosome components did not exhibit any enhanced susceptibility to phytoalexins and to applied stress conditions compared to the reference strain, except for a slight hypersensitivity of the ∆∆abpil1a-abpil1b strain to 2 M sorbitol. Depending on the considered mutants, we showed that the leaf and silique colonization processes were impaired by comparison to the wild-type, and assumed that these defects in aggressiveness were probably caused by a reduced appressorium formation rate. CONCLUSIONS: This is the first study on the role of MCC/eisosomes in the pathogenic process of a plant pathogenic fungus. A link between these membrane domains and the fungus ability to form functional penetration structures was shown, providing new potential directions for plant disease control strategies.

The effect of expectation on transcranial direct current stimulation (tDCS) to suppress food craving and eating in individuals with overweight and obesity.

Transcranial direct current stimulation (tDCS) is a neuromodulation technique with potential to treat eating disorders and obesity. As for any potential treatment, it is important to assess the degree to which expectation effects contribute to its reported efficacy. This study assessed the effect of tDCS on amount of food craving and eating while tightly controlling treatment expectation. N = 74 adults with overweight or obesity were informed of the known effects of tDCS to suppress craving and eating. Once electrodes were on the head, half of the participants were told they were receiving real, and the other half sham tDCS. Within these groups, approximately half actually received real and the other half sham tDCS. Stimulation parameters used were those previously found to reduce craving and eating, including in our lab: 2 mA, anode right/cathode left targeting the dorsolateral prefrontal cortex for 20 min (real), or only for the first and last minute (sham). Analyses controlled for demographics, hunger, trait impulsiveness, eating motives, dieting, binge eating, suggestibility, and baseline craving and eating. Participants told they were receiving real tDCS craved and ate less than participants told they were receiving sham tDCS (both p < 0.01), regardless of tDCS condition administered. There was no main effect of real vs. sham tDCS on craving or eating or an interaction between tDCS condition and expectation. The scientific validation of tDCS as a treatment for eating-related conditions hinges on controlling for the powerful effects of expectation. This can include the type of information provided on consent forms and participants' ability to guess real from sham conditions.

Awareness and Beliefs About Cervical Cancer, the HPV Vaccine, and Cervical Cancer Screening Among Ghanaian Women with Diverse Education Levels.

Cervical cancer is the leading cause of cancer death among women in Ghana. Cost-effective tools for the primary and secondary prevention of cervical cancer, such as the Pap test, the HPV DNA test, and the HPV vaccine, are available in hospitals and clinics throughout Ghana. However, participation in cervical cancer prevention behaviors is low among Ghanaian women. Our objective was to determine if there were significant differences in cervical cancer awareness and stigmatizing beliefs about women with cervical cancer between Ghanaian women of different education levels. We surveyed 288 Ghanaian women who were at least 18 years old. Data on the participants' demographic characteristics, awareness of cervical cancer, cervical cancer screening, and the HPV vaccine, beliefs about cervical cancer screening, and stigmatizing beliefs about women with cervical cancer was collected. Chi-square tests for independence and Fisher's exact test of independence were preformed to determine if education level was associated with those factors. Participation in cervical cancer screening and uptake of the HPV vaccine was significantly lower among women with less than a senior high school education. Awareness about cervical cancer, cervical cancer screening, and the HPV vaccine was lower among women with less education. Women with lower levels of education were more likely to agree with the negative statements about cervical cancer screening and stigmatizing beliefs about women with cervical cancer. Cervical cancer education interventions that are tailored for Ghanaian women with different educational levels are needed to increase awareness of and participation in cervical cancer prevention strategies.

Higher carbohydrate intake is associated with increased risk of all-cause and disease-specific mortality in head and neck cancer patients: results from a prospective cohort study.

No studies have evaluated associations between carbohydrate intake and head and neck squamous cell carcinoma (HNSCC) prognosis. We prospectively examined associations between pre- and post-treatment carbohydrate intake and recurrence, all-cause mortality, and HNSCC-specific mortality in a cohort of 414 newly diagnosed HNSCC patients. All participants completed pre- and post-treatment Food Frequency Questionnaires (FFQs) and epidemiologic surveys. Recurrence and mortality events were collected annually. Multivariable Cox Proportional Hazards models tested associations between carbohydrate intake (categorized into low, medium and high intake) and time to recurrence and mortality, adjusting for relevant covariates. During the study period, there were 70 deaths and 72 recurrences. In pretreatment analyses, high intakes of total carbohydrate (HR: 2.29; 95% CI: 1.23-4.25), total sugar (HR: 3.03; 95% CI: 1.12-3.68), glycemic load (HR: 2.10; 95% CI: 1.15-3.83) and simple carbohydrates (HR 2.26; 95% CI 1.19-4.32) were associated with significantly increased risk of all-cause mortality compared to low intake. High intakes of carbohydrate (HR 2.45; 95% CI: 1.23-4.25) and total sugar (HR 3.03; 95% CI 1.12-3.68) were associated with increased risk of HNSCC-specific mortality. In post-treatment analyses, medium fat intake was significantly associated with reduced risk of recurrence (HR 0.08; 95% CI 0.01-0.69) and all-cause mortality (HR 0.27; 95% CI 0.07-0.96). Stratification by tumor site and cancer stage in pretreatment analyses suggested effect modification by these factors. Our data suggest high pretreatment carbohydrate intake may be associated with adverse prognosis in HNSCC patients. Clinical intervention trials to further examine this hypothesis are warranted.

Two-Year Follow-Up of Impaired Range of Motion in Chronic Fatigue Syndrome.

OBJECTIVE: To measure changes in range of motion (ROM) over time in a cohort of 55 adolescents and young adults with chronic fatigue syndrome and to determine whether changes in ROM correlated with changes in health-related quality of life. STUDY DESIGN: Participants underwent a standardized examination of 11 areas of limb and spine ROM at baseline and at 3- to 6-month intervals for 2 years, resulting in a ROM score that ranged from 0 (normal throughout) to 11 (abnormal ROM in all areas tested). We measured the time until the ROM score was ≤2 (the score in healthy age-matched controls). Change in ROM was measured by subtracting the 24-month from the baseline ROM score and by summing the degrees of change in the 10 tests with continuous outcomes. Health-related quality of life was measured using the Pediatric Quality of Life Inventory 4.0 (PedsQL). RESULTS: The mean age at enrollment was 16.5 years (range 10-23). Two-year follow-up was available for 53 (96%). The proportion with a ROM score of >2 fell gradually over 2 years, from 78% at entry to 20% at 24 months (P < .001). ROM scores improved from a median of 5 at entry to 2 at 24 months (P < .001). The change in the summed degrees of improvement in ROM correlated positively with improvement in the PedsQL physical function subscale (r = 0.30; P < .03). CONCLUSIONS: In association with multimodal therapy, young people with chronic fatigue syndrome experienced progressively less impairment in ROM over 2 years, correlating with improvements in the physical function subscale of the PedsQL.

A Ketogenic Diet Reduces Central Obesity and Serum Insulin in Women with Ovarian or Endometrial Cancer.

Background: The glycolytic nature of cancer cells presents a potential treatment target that may be addressed by a ketogenic diet (KD). Objective: We hypothesized that a KD would improve body composition and lower serum insulin and insulin-like growth factor-I (IGF-I) in women with ovarian or endometrial cancer. Methods: In this randomized controlled trial, women with ovarian or endometrial cancer [age: ≥19 y; body mass index (kg/m2): ≥18.5] were randomly assigned to a KD (70:25:5 energy from fat, protein, and carbohydrate) or the American Cancer Society diet (ACS; high-fiber, low-fat). Body composition (DXA) and fasting serum insulin, IGF-I, and ß-hydroxybutyrate were obtained at baseline and at 12 wk; urinary ketones were also measured throughout the intervention. We assessed differences between the diets with ANCOVA and independent t tests. We used correlation analyses to estimate associations between changes in serum analytes and body composition. Results: After 12 wk, the KD (compared with ACS) group had lower adjusted total (35.3 compared with 38.0 kg, P < 0.05) and android (3.0 compared with 3.3 kg, P < 0.05) fat mass. Percentage of change in visceral fat was greater in the KD group (compared with the ACS group; -21.2% compared with -4.6%, P < 0.05). Adjusted total lean mass did not differ between the groups. The KD (compared with ACS) group had lower adjusted fasting serum insulin (7.6 compared with 11.2 µU/mL, P < 0.01). There was a significant inverse association between the changes in serum ß-hydroxybutyrate and IGF-I concentrations (r = -0.57; P < 0.0001). Conclusions: In women with ovarian or endometrial cancer, a KD results in selective loss of fat mass and retention of lean mass. Visceral fat mass and fasting serum insulin also are reduced by the KD, perhaps owing to enhanced insulin sensitivity. Elevated serum ß-hydroxybutyrate may reflect a metabolic environment inhospitable to cancer proliferation. This trial was registered at www.clinicaltrials.gov as NCT03171506.

Methodological and clinical implications of a three-in-one Russian doll design for tracking health trajectories and improving health and function through innovative exercise treatments in adults with disability.

BACKGROUND: Hybrid research designs targeting adults with neurologic disability are critical for improving the efficiency of models that can identify, track and intervene on identified health issues. METHODS: Our Russian doll framework encompasses three study phases. Phase 1 involves prospectively following a cohort of participants with disability to examine the relationships between rates of health and functional deficits (e.g., pain, fatigue, deconditioning), functional measures (e.g., cardiorespiratory endurance, strength, balance), and environmental and sociocultural factors. In Phase 2, eligible participants with neurologic disability from Phase 1 (in our example, individuals with multiple sclerosis) are screened and randomized to a clinical exercise efficacy trial. In Phase 3, study participants are enrolled in a home-based teleexercise trial to test the feasibility and replicability of delivering the clinical exercise study in the home. DISCUSSION: This unique three-in-one Russian doll framework serves as a foundation for informing and guiding researchers and clinicians in treating certain health and functional deficits in people with neurologic disability using exercise as a primary treatment modality in both the clinical and home settings. It offers a unique perspective for understanding the critical issues of functioning, health maintenance and quality of life for people with neurologic disability across a longitudinal framework. TRIAL REGISTRATION: Study 2 ClinicalTrials.gov identifier NCT02533882 (retroactively registered 03/06/2015). Study 3 ClinicalTrials.gov identifier NCT03108950 (retroactively registered 04/05/2017).

A qualitative study of cervical cancer and cervical cancer screening awareness among nurses in Ghana.

Despite the availability of cervical cancer screening tools, including those that are appropriate for low resource settings, the rates of preventive cervical cancer screening remain extremely low among women in LMICS. Nurse-led education interventions have been proven to be effective at increasing participation in healthcare recommendations. However, there is a need to determine nurses' knowledge of cervical cancer and cervical cancer prevention in order to develop effective health education interventions. Our goal was to assess Ghanaian nurses' knowledge of cervical cancer and cervical cancer prevention. Interviews and small focus groups were conducted with 42 nurses at two hospitals in Ghana. Awareness of cervical cancer was very high among the nurses. However, the majority of the participants held negative perceptions about cervical cancer and lacked knowledge about cervical cancer risk factors and prevention. The results can be used to inform the development of culturally-relevant cervical cancer education interventions targeted towards women and healthcare providers in LMICs.

Maximum Lifetime Body Mass Index and Mortality in Mexican American Adults: the National Health and Nutrition Examination Survey III (1988-1994) and NHANES 1999-2010.

INTRODUCTION: Studies in US Hispanic adults indicate no deleterious association between obesity and death. We tested the hypothesis that accounting for weight history would provide more insight into this nonassociation. METHODS: We used the National Health and Nutrition Examination Survey (NHANES) to examine associations between maximum lifetime body mass index (BMI) and all-cause and cause-specific mortality among US-residing Mexican American adults. BMI was classified as underweight (<18.5 kg/m2), normal weight (18.5-24.9), overweight (25.0-29.9), obese class I (30.0-34.9), and obese class II (≥35.0). We used Cox proportional hazards to examine the association between maximum lifetime BMI and BMI at survey and all-cause and specific causes of death (ie, cardiovascular disease, cancer, diabetes, and other) controlling for age, sex, and smoking in 6,242 Mexican American adults enrolled in NHANES III (1988-1994) and NHANES 1999-2010. RESULTS: Mexican Americans categorized as obese class II at maximum lifetime and time of survey had increased risk of all-cause mortality (hazard ratio [HR], 2.12; 95% confidence interval [CI], 1.54 - 2.93 and HR, 1.52; 95% CI, 1.10-2.10). Those reporting a maximum lifetime BMI of class I or class II obesity but who were classified as normal weight at survey had increased risk of all-cause mortality (HR = 2.49; 95% CI, 1.72-3.61 and HR = 3.56; 95% CI, 1.15-11.06, respectively). CONCLUSION: Increased all-cause mortality risk in Mexican Americans with a lifetime BMI of 35 or greater refutes prior studies, suggesting that maximum lifetime BMI should be included when evaluating obesity-mortality associations in this population.

Myths, presumptions, and facts about obesity.

BACKGROUND: Many beliefs about obesity persist in the absence of supporting scientific evidence (presumptions); some persist despite contradicting evidence (myths). The promulgation of unsupported beliefs may yield poorly informed policy decisions, inaccurate clinical and public health recommendations, and an unproductive allocation of research resources and may divert attention away from useful, evidence-based information. METHODS: Using Internet searches of popular media and scientific literature, we identified, reviewed, and classified obesity-related myths and presumptions. We also examined facts that are well supported by evidence, with an emphasis on those that have practical implications for public health, policy, or clinical recommendations. RESULTS: We identified seven obesity-related myths concerning the effects of small sustained increases in energy intake or expenditure, establishment of realistic goals for weight loss, rapid weight loss, weight-loss readiness, physical-education classes, breast-feeding, and energy expended during sexual activity. We also identified six presumptions about the purported effects of regularly eating breakfast, early childhood experiences, eating fruits and vegetables, weight cycling, snacking, and the built (i.e., human-made) environment. Finally, we identified nine evidence-supported facts that are relevant for the formulation of sound public health, policy, or clinical recommendations. CONCLUSIONS: False and scientifically unsupported beliefs about obesity are pervasive in both scientific literature and the popular press. (Funded by the National Institutes of Health.).

Packet randomized experiments for eliminating classes of confounders.

BACKGROUND: Although randomization is considered essential for causal inference, it is often not possible to randomize in nutrition and obesity research. To address this, we develop a framework for an experimental design-packet randomized experiments (PREs), which improves causal inferences when randomization on a single treatment variable is not possible. This situation arises when subjects are randomly assigned to a condition (such as a new roommate) which varies in one characteristic of interest (such as weight), but also varies across many others. There has been no general discussion of this experimental design, including its strengths, limitations, and statistical properties. As such, researchers are left to develop and apply PREs on an ad hoc basis, limiting its potential to improve causal inferences among nutrition and obesity researchers. METHODS: We introduce PREs as an intermediary design between randomized controlled trials and observational studies. We review previous research that used the PRE design and describe its application in obesity-related research, including random roommate assignments, heterochronic parabiosis, and the quasi-random assignment of subjects to geographic areas. We then provide a statistical framework to control for potential packet-level confounders not accounted for by randomization. RESULTS: Packet randomized experiments have successfully been used to improve causal estimates of the effect of roommates, altitude, and breastfeeding on weight outcomes. When certain assumptions are met, PREs can asymptotically control for packet-level characteristics. This has the potential to statistically estimate the effect of a single treatment even when randomization to a single treatment did not occur. CONCLUSIONS: Applying PREs to obesity-related research will improve decisions about clinical, public health, and policy actions insofar as it offers researchers new insight into cause and effect relationships among variables.

Weighing the Evidence of Common Beliefs in Obesity Research.

Obesity is a topic on which many views are strongly held in the absence of scientific evidence to support those views, and some views are strongly held despite evidence to contradict those views. We refer to the former as "presumptions" and the latter as "myths." Here, we present nine myths and 10 presumptions surrounding the effects of rapid weight loss; setting realistic goals in weight loss therapy; stage of change or readiness to lose weight; physical education classes; breastfeeding; daily self-weighing; genetic contribution to obesity; the "Freshman 15"; food deserts; regularly eating (versus skipping) breakfast; eating close to bedtime; eating more fruits and vegetables; weight cycling (i.e., yo-yo dieting); snacking; built environment; reducing screen time in childhood obesity; portion size; participation in family mealtime; and drinking water as a means of weight loss. For each of these, we describe the belief and present evidence that the belief is widely held or stated, reasons to support the conjecture that the belief might be true, evidence to directly support or refute the belief, and findings from randomized controlled trials, if available. We conclude with a discussion of the implications of these determinations, conjecture on why so many myths and presumptions exist, and suggestions for limiting the spread of these and other unsubstantiated beliefs about the obesity domain.

Impaired range of motion of limbs and spine in chronic fatigue syndrome.

OBJECTIVE: To determine whether adolescents and young adults with chronic fatigue syndrome (CFS) have a greater prevalence of impaired range of motion (ROM) of the limbs and spine than healthy control patients. STUDY DESIGN: Case-control study comparing rates of abnormal ROM in 48 consecutive adolescents and young adults with CFS and 48 healthy control patients matched by sex and joint hypermobility. We examined range of ankle dorsiflexion, passive straight-leg raise, seated slump, upper-limb neurodynamic test, prone knee bend, and prone press-up. Abnormal ROM was defined before the study began. The number of abnormal responses ranged from 0 (normal ROM throughout) to 11 (impaired ROM in all areas tested). RESULTS: The median number of areas with impaired ROM was greater in patients with CFS at the onset of stretch in the involved limb (5 vs 2, P<.001) and at end-range (2 vs 0, P<.001). Patients with CFS were more likely to have greater than 3 areas of impaired ROM (OR 6.0, 95% CI 2.1-17.3; P<.001) and were more likely to develop abnormal symptomatic responses to the individual tests and to the overall assessment (40% vs 4%; P<.001). CONCLUSIONS: Impaired ROM is more common in subjects with CFS than in healthy adolescents and young adults matched by sex and joint hypermobility. Adding a longitudinal strain to the nerves and soft tissues provoked symptoms in some subjects with CFS. The causes, functional impact, and optimal treatment of these abnormalities warrant further study.

Muscle density in rheumatoid arthritis: associations with disease features and functional outcomes.

OBJECTIVE: To explore the associations between measures of body composition derived from computed tomography (CT) of the thigh and functional outcomes in patients with rheumatoid arthritis (RA). METHODS: Patients with RA underwent bilateral midfemoral quantitative CT for measurement of thigh fat area (TFA), thigh muscle area (TMA), and thigh muscle density (TMD). The associations of thigh-composition measures with disability and physical performance, as measured with the Health Assessment Questionnaire (HAQ), the Valued Life Activities (VLAs), and the Short Physical Performance Battery (SPPB) instruments, were explored in the total cohort and in the cohort subgrouped by sex, controlling for pertinent demographic, lifestyle, and RA disease and treatment covariates. RESULTS: A total of 152 RA patients were studied. Among the potential determinants of TMD, older age, longer duration of sedentary activity, longer duration of RA, higher tender joint count, higher serum interleukin-6 levels, use of glucocorticoids, and nonuse of hydroxychloroquine were all significantly associated with lower TMD in multivariable models. RA characteristics accounted for 63% of the explainable variability in TMD. When comodeled, higher TFA and lower TMD, but not lower TMA, were significantly and independently associated with higher HAQ scores, lower Short Form 36 health survey physical functioning scores, lower composite SPPB scores, and a greater proportion of affected obligatory VLAs. CONCLUSION: Thigh CT-derived measures of body composition, particularly fat area and muscle density, were strongly associated with disability and physical performance in RA patients, with RA disease features as potential determinants. Efforts to reduce fat and improve muscle quality may reduce disability in this population with impaired physical functioning.