Search

Abstract: Several reports suggest that folate has a procarcinogenic effect. Folate has a unique role because its coenzymes are needed for de novo purine and thymine nucleotide biosynthesis. Antifolates, such as methotrexate, are used in cancer treatment. Using a meta-analysis weighted for the duration of folic acid (pteroylglutamic acid) supplementation, we analyzed the cancer incidence of six previously published large prospective folic acid-supplementation trials in men and women. These articles were carefully selected from over 1100 identified using PubMed search. Our analyses suggest that cancer incidences were higher in the folic acid-supplemented groups than the non-folic acid-supplemented groups (relative risk=1.21 [95% confidence interval: 1.05–1.39]). Folic acid-supplementation trials should be performed with careful monitoring of cancer incidence. Solid monitoring systems to detect side effects, including increase in cancer risk, should be established before the initiation of folic acid supplementation trials. [Copyright &y& Elsevier]

OBJECTIVE: To determine if folinic acid supplementation during methotrexate (MTX) therapy for rheumatoid arthritis (RA) reduces both urinary 5-aminoimidazole-4-carboxamide (AICA) and urinary adenosine excretion more than does folic acid supplementation. AICA and adenosine are markers for MTX interference with purine metabolism. METHODS: Forty patients with RA who received MTX for 6 weeks were randomized to receive either daily folic acid or folinic acid supplements during an additional week of MTX therapy. Colorimetric and radioimmunocompetition assays were used to measure 24-hour urinary AICA and adenosine excretion levels, respectively. RESULTS: At the end of 6 weeks, 24-hour urinary levels of AICA, but not adenosine, were elevated as compared with baseline levels (i.e., prior to MTX therapy). Folinic acid, but not folic acid, supplementation normalized urinary AICA levels during MTX therapy. Relatively high urinary levels of AICA were correlated with reduced disease activity. No similar correlations were seen with urinary adenosine levels. CONCLUSION: The blockade of purine nucleotide biosynthesis by MTX at the AICA ribonucleotide transformylase-catalyzed step may be related to the efficacy of MTX, and this blockade is effectively relieved by folinic acid, but not by folic acid, supplementation. Copyright 2004 American College of Rheumatology [ABSTRACT FROM AUTHOR]

The purpose of this study is to examine the relationship of a rural clerkship to medical students' interest in establishing careers in rural communities. The Association of American Medical Colleges Medical School Graduation Questionnaire (GQ) for years 1988 through 1997 was examined to compare the career plans of students graduating from Morehouse School of Medicine (MSM) with those of all students graduating from United States medical schools before the period 1988 through 1992 and after the period 1993 through 1997, after the inception of the rural clerkship at MSM. Select GQ data items examined include student demographics, medical school experiences, and career plans. Statistical analyses were used to compare pre- and post-clerkship responses for MSM students and to compare their responses with the national trends. Results indicate that, following a transition period, MSM students showed an increased preference for a future career in a rural community. A smaller upward trend in the national data was observed. There appears to be an association between the rural clerkship experience at MSM and the stated preferred career choices of the students. [ABSTRACT FROM AUTHOR]

Background: Considering the need to increase HIV testing among racial minority youth in the southern United States, we conducted an exploratory study in Alabama to elucidate recommendations on improving testing rates among Black young men who have sex with men (BYMSM)., Methods: We conducted in-depth interviews and focus groups with BYMSM and prevention and outreach workers. Data collection occurred online and in person between 2020-2022., Results: Our sample included data from n = 56 BYMSM and n = 12 prevention and outreach workers. BYMSMs' mean age = 24 years. Among prevention and outreach workers, 58% identified as male with mean age = 39 years; 83% identified as Black. Transcripts were coded thematically; five concurrent themes emerged from both BYMSM and prevention and outreach workers: promoting testing at younger ages, need for visibility and outreach, connecting through shared experiences, value of nonjudgmental approaches, and need to increase HIV knowledge in BYMSM., Conclusions: Findings suggest that cultivating trust is salient to promoting HIV testing in BYMSM. To end the epidemic in the southern United States, a region that is heavily rural with high rates of HIV, it may be necessary to begin prevention conversations at younger ages and equip prevention and outreach workers with communication skills that leverage de-stigmatizing approaches., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: Exercise program preferences are important for designing physical activity (PA) interventions; yet may change following an intervention. Further, the relationship between preferences and PA behavior change is unclear. This study evaluated exercise program preferences among breast cancer survivors (BCS) before and after a behavioral intervention and associations between program preferences and PA change., Methods: BCS were randomized to the BEAT Cancer intervention (n = 110) or written materials (n = 112). Questionnaires assessed exercise program preferences. Minutes per week of moderate-to-vigorous PA (MVPA) were accelerometer-measured and self-reported at baseline (M0), post-intervention (M3), and 3-month follow-up (M6)., Results: At M0, the majority of intervention group participants preferred exercising with others (62%) yet shifted to preferring exercising alone (59%) at M3 (p < 0.001). Furthermore, preferring exercising with others at M0 was associated with greater increases in self-reported MVPA between M0 and M6 (124.2 ± 152 vs. 53.1 ± 113.8, p = 0.014). BCS preferring facility-based exercise decreased after the BEAT Cancer intervention (14% vs. 7%, p = 0.039) and preferring exercising at home/had no preference at M0 had greater improvements in accelerometer-measured MVPA from M0 to M3 (74.3 ± 118.8 vs. -2.3 ± 78.4, p = 0.033) and M0 to M6 (44.9 ± 112.8 vs. 9.3 ± 30.4, p = 0.021). Exercise program preferences regarding mode of counseling, training supervision, and type of exercise changed from M0 to M3 but were not associated with changes in MVPA., Conclusion: Findings suggest BCS exercise program preferences may change after an intervention and be associated with changes in MVPA. Understanding the role of PA preferences will better inform the design and success of PA behavior change interventions. ClinicTrials.gov, ClinicalTrials.gov number: NCT00929617., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Importance: Cancer survivors experience accelerated functional decline that threatens independence and quality of life. Previous studies have suggested that vegetable gardening may improve diet, physical activity, and physical function in this vulnerable population, which comprises more than 5% of the US population., Objective: To assess whether diet, physical activity and functioning, and other outcomes improved in older cancer survivors assigned to a vegetable gardening intervention compared with a waitlist., Design, Setting, and Participants: From May 11, 2016, to May 2, 2022, a 2-arm, assessor-blinded, crossover-designed, intent-to-treat, randomized clinical trial was conducted at cancer survivors' homes across Alabama. Medicare-eligible survivors of cancers with 5-year survival of 60% or more were registry ascertained and screened for suboptimal vegetable and fruit consumption (<5 servings per day), physical activity (<150 moderate-to-vigorous minutes per week), and physical function (36-Item Short Form Health Survey [SF-36] subscale score ≤90). Consented participants underwent baseline assessments, were randomly assigned to intervention or waitlisted arms, and were reassessed at 1-year follow-up., Intervention: One-year, home-based vegetable gardening intervention providing gardening supplies and mentorship by cooperative extension-certified master gardeners to plant and maintain spring, summer, and fall gardens. Waitlisted participants received the identical intervention after 12 months., Main Outcomes and Measures: The main outcome was a composite index of improvements in self-reported vegetable and fruit consumption, physical activity, and physical function corroborated by plasma α-carotene levels, accelerometry, and physical performance assessments, respectively., Results: Of 381 enrolled participants (mean [SD] age, 69.8 [6.4] years; range, 50-95 years; 263 [69.0%] female), 194 were assigned to the gardening intervention and 187 were waitlisted (attrition rates, 7.2% and 7.0%, respectively). Intent-to-treat analyses did not detect a significant improvement in the composite index of vegetable and fruit intake, moderate-vigorous physical activity, and physical function (intervention arm vs waitlisted arm, 4.5% vs 3.1%; P = .53) or between-arm differences in vegetable and fruit intake (mean difference, 0.3 [95% CI, -0.1 to 0.7] servings per day; P = .10). The intervention arm experienced a significant improvement in vegetable and fruit intake (mean increase, 0.3 [95% CI, 0.0-0.6] servings per day; P = .04). Significant improvements also were observed in the intervention arm vs waitlisted arm in physical performance (mean difference for 2-minute step test, 6.0 [95% CI, 0.8-11.2] steps; P = .03; for 30-second chair stand, 0.8 [95% CI, 0.1-1.5] repetitions; P = .02), perceived health (8.4 [95% CI, 3.0-13.9] points on a 100-point scale [higher scores indicate better health]; P = .003), and gut microbiome alpha diversity (84.1 [95% CI, 20.5-147.6] more observed species; P = .01). The COVID-19 pandemic significantly moderated effects (eg, odds of improvement in self-reported physical functioning were greater before vs during the pandemic: odds ratio, 2.17; 95% CI, 1.12-4.22; P = .02)., Conclusions and Relevance: In this randomized clinical trial including older cancer survivors, a vegetable gardening intervention did not significantly improve a composite index of diet, physical activity, and physical function; however, survivors assigned to the intervention had significantly increased vegetable and fruit consumption and, compared with waitlisted survivors, experienced significant improvements in perceived health and physical performance. Further study in broader populations and during pandemic-free periods is needed to determine definitive benefits., Trial Registration: ClinicalTrials.gov Identifier: NCT02985411.

Ameloblastomas are benign neoplasms of the jaw, but frequently require extensive surgery. The aim of the study was to analyze the demographic and clinicopathological features of ameloblastoma cases at a single Oral and Maxillofacial Surgery group in the United States., Study Design: A retrospective chart review of patients evaluated for ameloblastoma between 2010 and 2020 at a single tertiary care center. Age, race, sex, tumor size, tumor location, and histological subtypes were recorded., Results: A total of 129 cases of ameloblastoma were recorded with a mean patient age of 42 ± 18.6 years (range 9-91 years old), male to female ratio 1.08:1. Ameloblastoma presenting in the mandible outnumbered maxilla in primary (118 to 8, respectively) and recurrent cases (8 to 1, respectively). There was a higher prevalence of ameloblastoma in Black patients (61.3%) with mean age of Black patients occurring at 40.5 years and the mean age of White patients occurring at 47.8 years and mean tumor size trended larger in the Black patients (15.7 cm 2 ) compared to White patients (11.8 cm 2 )., Conclusion: Data suggests a strong influence of racial factors on the incidence of ameloblastoma, with regards to size, Black patients with ameloblastoma trended higher and more data is needed to clearly elucidate any relationship between the tumor size and race, as other factors may influence the size (such as time to discovery)., (© 2024. The Author(s).)

Background: Children with mobility disabilities, including those with cerebral palsy, have limited options and limited time to exercise to manage their cardiometabolic health and cardiorespiratory fitness. Regular cardiovascular exercise during childhood is a critical health behavior for preventing health decline in adulthood. Thus, there is an urgent need for accessible, age-appropriate, convenient exercise modalities in this group. Sprint-intensity interval training (SIT), combined with telehealth procedures, may be ideal for children with disabilities. SIT includes repetitive bouts of maximal exercise effort combined with rest periods, which can be effective in eliciting comparable results to moderate-exercise training with very short training durations., Objective: This phase 1 pilot feasibility randomized controlled trial aims to investigate the potential effects of a 12-week SIT program on indicators of cardiorespiratory fitness and cardiometabolic health among children with cerebral palsy. An ancillary aim is to evaluate the feasibility of the program through several process feasibility metrics., Methods: This study uses a 2-armed parallel group design. A total of 50 physically inactive children with cerebral palsy (aged 6-17 years) will be randomly allocated into 1 of 2 groups: a 12-week SIT or a waitlist control group that continues habitual activity for 12 weeks. The SIT prescription includes 3 tele-supervised sessions per week with 30 repeated sequences of 4 seconds of maximal arm exercise, with active recovery, warm-up, and cooldown periods (for an approximately 20-minute total session). SIT includes guided videos with child-themed arm routines and music. The exercise sessions will be remotely supervised through a web-based videoconference application and include safety monitoring equipment. Outcomes are measured at pre- and postintervention (weeks 0 and 13, respectively). Health outcome measures include peak oxygen consumption (VO 2 peak), measured by a graded exercise test; high-sensitivity C-reactive protein and blood insulin, hemoglobin A 1c , triglycerides, and cholesterol using a finger stick dried blood spot test; blood pressure, using a sphygmomanometer; and body composition (total mass, total lean mass, tissue % lean, and tissue % fat) using dual x-ray absorptiometry. Feasibility will be evaluated by the following metrics: adverse events or problems experienced throughout the intervention related to participant safety; perceived enjoyment; and recruitment, enrollment, and attrition rates., Results: Recruitment procedures started in November 2023. All data are anticipated to be collected by February 2025. Full trial results are anticipated to be analyzed and submitted for publication by March 2025. Secondary analyses of data will be subsequently published., Conclusions: This trial tests an accessible and low-cost exercise program that leverages principles of high-intensity exercise to provide a convenient program for children with physical disabilities. Knowledge obtained from this study will inform the development of a larger trial for improving the cardiometabolic health, cardiorespiratory fitness, and well-being of children with physical disabilities., Trial Registration: ClinicalTrials.gov NCT05619211; https://clinicaltrials.gov/study/NCT05619211., International Registered Report Identifier (irrid): DERR1-10.2196/56499., (©Byron Lai, Robert A Oster, Drew Davis, Larsen Bright, Gordon Fisher, Jereme Wilroy, Yumi Kim, Raven Young, Ashley Wright, Tanvee Sinha, James H Rimmer. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 05.03.2024.)

Inflammation is thought to contribute to the etiology of interstitial cystitis/bladder pain syndrome (IC/BPS). It is well-known that disruption in metabolism in immune cells contributes to inflammation in several inflammatory diseases. The purpose of this study was to investigate whether cellular bioenergetics is altered in monocytes and lymphocytes from women with IC/BPS, and if these alterations correlate with systemic inflammatory markers. Age and BMI matched adult healthy women (HS; n = 18) and women with IC/BPS (n = 18) were included in the study. Blood was collected to assess cellular bioenergetics in monocytes and lymphocytes using a Seahorse XF96 Analyzer and plasma cytokine levels were measured using Meso Scale Discovery immunoassays. The correlation between bioenergetic parameters, cytokines, and demographics was determined using Pearson correlation coefficients. Means of the two groups were compared using the two-group t-test. Patients with IC/BPS had reduced monocyte oxygen consumption rates and glycolytic rates compared to healthy subjects. In contrast, lymphocytes from these patients had increased oxygen consumption rates and glycolytic rates. Several cytokines and chemokines including Interferon-gamma (IFN-ɣ), tumor necrosis factor alpha (TNF-ɑ), Interleukin-6 (IL-6), Interleukin-8 (IL-8) and vascular endothelial growth factor (VEGF) levels were significantly elevated in the plasma of patients with IC/BPS. However, Transforming growth factor (TGF-β) and Interleukin-10 (IL-10) levels were significantly decreased in IC/BPS patients compared to HS. In addition, Interferon gamma (IFN-ɣ), TNF-ɑ, IL-8, and TGF-β levels correlated with several bioenergetic parameters in monocytes or lymphocytes from healthy subjects. In contrast, TNF-ɑ and IL-8 correlated with bioenergetic parameters in monocytes from IC/BPS patients. Monocyte and lymphocyte cellular bioenergetics and plasma cytokine levels are different in patients with IC/PBS compared to HS. It appears that systemic inflammation is greater in this cohort which may negatively impact immune cell function. The relationship between cellular bioenergetics and inflammation in monocytes and lymphocytes could be important in understanding the pathogenesis of IC/PBS and warrants further investigation., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Kumar et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Vancomycin loading doses are commonly used to quickly attain target serum concentrations; however, data supporting their effect on clinical patient outcomes is limited. In April 2020, our institution revised our pharmacist-driven vancomycin dosing protocol to reserve loading doses for hemodynamically unstable patients with suspected serious methicillin-resistant Staphylococcus aureus (MRSA) infections. Prior to the protocol update, all patients treated with vancomycin at our institution received a weight-based loading dose. The purpose of this study is to assess clinical efficacy and safety outcomes related to the use of vancomycin loading doses. Methods: A retrospective, quasi-experimental study was performed to compare clinical outcomes in adult patients treated with vancomycin for laboratory-confirmed MRSA infections. Patients who received vancomycin therapy prior to our institution's vancomycin dosing protocol revisions (pre-intervention) were compared to patients who received vancomycin after the revisions (post-intervention). The primary outcome was all-cause, inpatient mortality. Secondary outcomes included persistent signs and symptoms of infection ≥5 days after vancomycin initiation, switch to alternative anti-MRSA therapy, and nephrotoxicity. Results: A total of 122 patients (63 pre-intervention patients and 59 post-intervention patients) were included. Receipt of a vancomycin loading dose did not impact the rate of inpatient mortality (4.76%vs 6.78%; OR 1.46, 95% CI [0.31, 6.79]). All secondary outcomes were similar between the two groups, including persistent signs and symptoms of infection, switch to alternative anti-MRSA therapy, and nephrotoxicity. Conclusions: Routine use of vancomycin loading doses is not associated with improved outcomes in hemodynamically stable patients with MRSA infections., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

Background: Consensus guidelines for dosing and monitoring of vancomycin recommend collection of 2 serum concentrations to estimate an area under the curve/minimum inhibitory concentration ratio (AUC/MIC). Use of Bayesian software for AUC estimation and model-informed precision dosing (MIPD) enables pre-steady state therapeutic drug monitoring using a single serum concentration; however, data supporting this approach are limited., Methods: Adult patients with culture-proven gram-positive infections treated with vancomycin ≥72 hours receiving either trough-guided or AUC-guided therapy were included in this retrospective study. AUC-guided therapy was provided using MIPD and single-concentration monitoring. Treatment success, vancomycin-associated acute kidney injury (VA-AKI), and inpatient mortality were compared using a desirability of outcome ranking analysis. The most desirable outcome was survival with treatment success and no VA-AKI, and the least desirable outcome was death., Results: The study population (N = 300) was comprised of an equal number of patients receiving AUC-guided or trough-guided therapy. More patients experienced the most desirable outcome in the AUC-guided group compared to the trough-guided group (58.7% vs 46.7%, P = .037). Rates of VA-AKI were lower (21.3% vs 32.0%, P = .037) and median hospital length of stay was shorter (10 days [interquartile range {IQR}, 8-20] vs 12 days [IQR, 8-25]; P = .025) among patients receiving AUC-guided therapy., Conclusions: AUC-guided vancomycin therapy using MIPD and single-concentration monitoring improved outcomes in patients with culture-proven gram-positive infections. Safety was improved with reduced incidence of VA-AKI, and no concerns for reduced efficacy were observed. Moreover, MIPD allowed for earlier assessment of AUC target attainment and greater flexibility in the collection of serum vancomycin concentrations., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Research articles in the clinical and translational science literature commonly use quantitative data to inform evaluation of interventions, learn about the etiology of disease, or develop methods for diagnostic testing or risk prediction of future events. The peer review process must evaluate the methodology used therein, including use of quantitative statistical methods. In this manuscript, we provide guidance for peer reviewers tasked with assessing quantitative methodology, intended to complement guidelines and recommendations that exist for manuscript authors. We describe components of clinical and translational science research manuscripts that require assessment including study design and hypothesis evaluation, sampling and data acquisition, interventions (for studies that include an intervention), measurement of data, statistical analysis methods, presentation of the study results, and interpretation of the study results. For each component, we describe what reviewers should look for and assess; how reviewers should provide helpful comments for fixable errors or omissions; and how reviewers should communicate uncorrectable and irreparable errors. We then discuss the critical concepts of transparency and acceptance/revision guidelines when communicating with responsible journal editors., Competing Interests: CJL receives research funding to his institution from NIH, DoD, CDC, Biomeme, Entegrion, Endpoint Health, AstraZeneca, bioMerieux, and stock options in Bioscape Digital unrelated to the current work., (© The Author(s) 2024.)

Objective: External apical root resorption (EARR) is a side effect of orthodontic treatment that results in root shortening. However, this condition has yet to be evaluated in African Americans. The aim of this study was to determine the EARR prevalence within this ethnicity and investigate how patient and treatment-related factors contribute to root resorption., Methods: The records of 336 African Americans treated at the University of Alabama at Birmingham School of Dentistry Department of Orthodontics were retrospectively analyzed with Dolphin Imaging software. Pre-treatment and post-treatment panoramic radiographs were used to measure EARR. Resorption was recorded when final roots were at least 2 mm shorter after orthodontic treatment. Additionally, moderate and severe EARR was reported when 20% and 50% or more of the root structure was lost for any of the four maxillary incisors, respectively. The Pearson chi-square test was used to evaluate the associations of individual patient and treatment-related factors with EARR., Results: The prevalence of root resorption with 2 mm or greater of root structure loss was 51.8%. The prevalence of ≥ 20% EARR was 29.8%. Only one patient displayed severe resorption (0.3%). The associations between the patient-specific and treatment-specific variables and EARR were not statistically significant (P > .05)., Conclusions: More than half of the African American patients exhibit at least 2 mm of root resorption with orthodontic treatment. However, in this ethnicity, patient-related factors such as age, gender, dental malocclusion, and skeletal classifications, as well as treatment-related factors do not indicate a significant correlation with the risk of developing EARR., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Orthodontic Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Despite well-documented global declines in physical activity (PA) during the COVID-19 pandemic, little is known regarding the specific impact among underserved, rural Alabama counties. This is concerning as this region was already disproportionately burdened by inactivity and related chronic diseases and was among the hardest hit by COVID-19. Thus, the current study examined the effect of COVID-19 on PA in four rural Alabama counties. An ancillary survey was administered between March 2020 and August 2021 to the first cohort (N = 171) of participants enrolled in a larger PA trial. Main outcomes of this survey included the perceived impact of COVID-19 on PA, leisure-time PA, and social cognitive theory (SCT) constructs at 3 months. Almost half of the participants reported being less active during the pandemic (49.7%) and endorsed that COVID-19 made PA more difficult (47.4%), citing concerns such as getting sick from exercising outside of the home (70.4%) and discomfort wearing a face mask while exercising (58%). Perceived COVID-19 impact on PA was significantly associated with education, household dependents, and gender ( p 's < 0.05). More women, parents, and college graduates reported that the COVID-19 pandemic made PA more difficult. Overall, there were no significant associations between PA, SCT constructs, or perceived COVID-19 impact on PA scores at 3 months. While the pandemic made PA difficult for many participants, these barriers were not associated with leisure-time PA levels or related theoretical mechanisms of action, which bodes well for the success of our ongoing intervention efforts and the resiliency of these communities.

Purpose: Determine durable effects of the 3-month Better Exercise Adherence after Treatment for Cancer (BEAT Cancer) physical activity (PA) behavior change intervention 12 months post-baseline (i.e., 9 months after intervention completion)., Methods: This 2-arm multicenter trial randomized 222 post-primary treatment breast cancer survivors to BEAT Cancer (individualized exercise and group education) vs. usual care (written materials). Assessments occurred at baseline, 3, 6, and 12 months, with the 12 months assessment reported here. Measures included PA (accelerometer, self-report), cardiorespiratory fitness, muscle strength, body mass index, Functional Assessment of Cancer Therapy (FACT), SF-36, fatigue, depression, anxiety, satisfaction with life, Pittsburgh Sleep Quality Index (PSQI), lower extremity joint dysfunction, and perceived memory., Results: Adjusted linear mixed-model analyses demonstrated statistically significant month 12 between-group differences favoring BEAT Cancer for weekly minutes of moderate-to-vigorous self-report PA (mean between-group difference (M) = 44; 95% confidence interval (CI) = 12 to 76; p = .001), fitness (M = 1.5 ml/kg/min; CI = 0.4 to 2.6; p = .01), FACT-General (M = 3.5; CI = 0.7 to 6.3; p = .014), FACT-Breast (M = 3.6; CI = 0.1 to 7.1; p = .044), social well-being (M = 1.3; CI = 0.1 to 2.5; p = .037), functional well-being (M = 1.2; CI = 0.2 to 2.3; p = .023), SF-36 vitality (M = 6.1; CI = 1.4 to 10.8; p = .011), fatigue (M =  - 0.7; CI =  - 1.1 to - 0.2; p = .004), satisfaction with life (M = 1.9; CI = 0.3 to 3.5; p = .019), sleep duration (M =  - 0.2; CI =  - 0.4 to - 0.03, p = .028), and memory (M = 1.1; CI = 0.2 to 2.1; p = .024)., Conclusions: A 3-month PA intervention resulted in statistically significant and clinically important benefits compared to usual care at 12 months., Implications for Cancer Survivors: Three months of individualized and group PA counseling causes benefits detectable 9 months later., Trial Registration: ClinicalTrials.gov NCT00929617 ( https://clinicaltrials.gov/ct2/show/NCT00929617 ; registered June 29, 2009)., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Children with sickle cell disease (SCD) frequently present with acute pain. The abdomen, a common site of acute SCD-related pain, may be present in a variety of gastrointestinal (GI) pathologies. Limited data exist on prevalence and workup of abdominal pain in patients with SCD during acute pain events., Objectives: Determine prevalence of GI symptoms, GI-specific evaluation and risks of hospitalization in children with SCD presenting to the emergency department (ED) or hospitalized with abdominal pain., Methods: Retrospective study of children less than 21 years presenting to the ED or hospitalized with pain in our center over 2 years. Descriptive statistics were used to report clinical characteristics, frequency of GI symptoms, workup by age (<5 vs. ≥5 years), and genotype (sickle cell anemia [SCA] vs. non-SCA). Logistic regression models were used to identify risks associated with hospitalization., Results: A total of 1279 encounters in 378 patients were analyzed; 23% (n = 291) encounters were associated with abdominal pain. More abdominal pain-associated hospitalizations occurred in older children, SCA, children with lower mean hemoglobin (8.7 ± 1.9 vs. 9.6 ± 1.6 g/dL, p < .001) and higher mean white blood cell (WBC) count (14.9 ± 6.6 vs. 13.2 ± 5.3 × 10 3 /μL, p = .02). We identified that less than 50% of patients presenting to the ED with abdominal pain received a GI-specific evaluation., Conclusion: Children with SCD frequently present with abdominal pain and other GI symptoms, with limited GI evaluations performed. GI-specific evaluation may increase diagnosis of GI pathologies, rule out GI pathologies, and contribute to the limited knowledge of the abdomen as a primary site of SCD pain., (© 2023 Wiley Periodicals LLC.)

Introduction: Despite the critical role that quantitative scientists play in biomedical research, graduate programs in quantitative fields often focus on technical and methodological skills, not on collaborative and leadership skills. In this study, we evaluate the importance of team science skills among collaborative biostatisticians for the purpose of identifying training opportunities to build a skilled workforce of quantitative team scientists., Methods: Our workgroup described 16 essential skills for collaborative biostatisticians. Collaborative biostatisticians were surveyed to assess the relative importance of these skills in their current work. The importance of each skill is summarized overall and compared across career stages, highest degrees earned, and job sectors., Results: Survey respondents were 343 collaborative biostatisticians spanning career stages (early: 24.2%, mid: 33.8%, late: 42.0%) and job sectors (academia: 69.4%, industry: 22.2%, government: 4.4%, self-employed: 4.1%). All 16 skills were rated as at least somewhat important by > 89.0% of respondents. Significant heterogeneity in importance by career stage and by highest degree earned was identified for several skills. Two skills ("regulatory requirements" and "databases, data sources, and data collection tools") were more likely to be rated as absolutely essential by those working in industry (36.5%, 65.8%, respectively) than by those in academia (19.6%, 51.3%, respectively). Three additional skills were identified as important by survey respondents, for a total of 19 collaborative skills., Conclusions: We identified 19 team science skills that are important to the work of collaborative biostatisticians, laying the groundwork for enhancing graduate programs and establishing effective on-the-job training initiatives to meet workforce needs., Competing Interests: The authors have no conflicts of interest to declare., (© The Author(s) 2023.)

Despite exercise benefits for cancer survivor health, most breast cancer survivors do not meet exercise recommendations. Few studies have examined associations between psychosocial symptoms and exercise barriers in this population. To improve physician exercise counseling by identifying survivors with high barriers in a clinical setting, associations between breast cancer symptoms (fatigue, mood, sleep quality) and exercise barriers were investigated. Physically inactive survivors ( N = 320; average age 55 ± 8 years, 81% White, 77% cancer stage I or II) completed a baseline survey for a randomized physical activity trial and secondary analyses were performed. Potential covariates, exercise barriers interference score, Fatigue Symptom Inventory, Hospital Anxiety and Depression Scale (HADS), and Pittsburgh Sleep Quality Index were assessed. Based on multiple linear regression analyses, only HADS Global (B = 0.463, p < 0.001) and number of comorbidities (B = 0.992, p = 0.01) were independently associated with total exercise barriers interference score, explaining 8.8% of the variance (R 2 = 0.088, F(2,317) = 15.286, p < 0.001). The most frequent barriers to exercise for survivors above the HADS clinically important cut point included procrastination, routine, and self-discipline. These results indicate greater anxiety levels, depression levels, and comorbidities may be independently associated with specific exercise barriers. Health professionals should consider mood and comorbidities when evaluating survivors for exercise barriers, and tailoring exercise counseling.

Background and Purpose: The aim of this study was to assess the repeatability of neurite orientation dispersion and density imaging in healthy controls (HCs) and traumatic brain injury (TBI)., Methods: Seventeen HCs and 48 TBI patients were scanned twice over 18 weeks with diffusion imaging. Orientation dispersion (ODI), neurite density (NDI), and the fraction of isotropic diffusion (F-ISO) were quantified in regions of interest (ROIs) from a gray matter, subcortical, and white matter atlas and compared using the coefficient of variation for repeated measures (CV rep ), which quantifies the expected percent change on repeated measurement. We used a modified signed likelihood ratio test (M-SLRT) to compare the CV rep between groups in each ROI while correcting for multiple comparisons., Results: NDI exhibited excellent repeatability in both groups; the only group difference was found in the fusiform gyrus, where HCs exhibited better repeatability (M-SLRT = 9.463, p = .0021). ODI also had excellent repeatability in both groups, although repeatability was significantly better in HCs in 16 cortical ROIs (p < .0022) and in the bilateral white matter and bilateral cortex (p < .0027). F-ISO exhibited relatively poor repeatability in both groups, with few group differences., Conclusion: Overall, the repeatability of the NDI, ODI, and F-ISO metrics over an 18-week period is acceptable for assessing the effects of behavioral or pharmacological interventions, though caution is advised when assessing F-ISO changes over time., (© 2023 The Authors. Journal of Neuroimaging published by Wiley Periodicals LLC on behalf of American Society of Neuroimaging.)

Introduction: Despite modern advances in surgical and perioperative technologies, management of renal cell carcinoma (RCC) with tumor thrombus (TT) is a morbid procedure that necessitates careful patient selection. It is not known whether established prognostic models for metastatic RCC are suitable prognostic tools for more immediate perioperative outcomes in patients with RCC with TT. We evaluated if established risk models for cytoreductive nephrectomy, as a potential extension of their purpose-built use, are associated with immediate perioperative outcomes in patients undergoing nephrectomy and tumor thrombectomy., Methods: Perioperative outcomes of patients who underwent radical nephrectomy and tumor thrombectomy for RCC were compared to presences of established predictors of long-term outcomes from prior risk models individually and as stratified by risk grouping (International Metastatic Renal-Cell Carcinoma Database Consortium [IMDC], Memorial Sloan Kettering Cancer Center [MSKCC], M.D. Anderson Cancer Center [MDACC], and Moffitt Cancer Center [MCC]). Wilcoxon rank-sum test or the Kruskal-Wallis test compared continuous variables and the chi-square test or Fisher's exact test compared categorical variables., Results: Fifty-five patients were analyzed with 17 (30.9%) being cytoreductive. Eighteen (32.7%) patients had a level III or higher TT. Individually, preoperative variables were inconsistently associated with perioperative outcomes. Poorer risk patients per the IMDC model had more major postoperative complications (Clavien-Dindo grade≥3, P = 0.008). For the MSKCC model, poorer risk patients had increased intraoperative estimated blood loss (EBL), longer length of stay (LOS), more major postoperative complications, and more likely to discharge to a rehabilitation facility (P < 0.05). Less favorable risk patients per MDACC model had increased LOS (P = 0.038). Poorer risk patients per the MCC model had increased EBL, LOS, major postoperative complications, and 30-day hospital readmissions (P < 0.05)., Conclusion: Overall, cytoreductive risks models were heterogeneously associated with perioperative outcomes in patients undergoing nephrectomy and tumor thrombectomy. Of available models, the MCC model is associated with more perioperative outcomes including EBL, LOS, major postoperative complications, and readmissions within 30 days when compared to the IMDC, MSKCC, and MDACC models., Competing Interests: Declaration of Competing Interest Soroush Rais-Bahrami serves as a consultant to Philips/InVivo Corp, Lantheus, Genomic Health Inc, Blue Earth Diagnostics, Bayer Healthcare, UroViu Corp, and Intuitive Surgical. Jeffrey W. Nix serves as a consultant for Philips Corp and Intuitive Surgical. All remaining authors report no other potential conflicts of interest or financial disclosures that were pertinent to the following study., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: To facilitate replication and future intervention design of web-based multibehavior lifestyle interventions, we describe the rationale, development, and content of the A i M , P lan, and act on LIF est Y les (AMPLIFY) Survivor Health intervention which provides healthy eating and exercise behavior change support for older cancer survivors. The intervention promotes weight loss, improvements in diet quality, and meeting exercise recommendations., Methods: The Template for Intervention Description and Replication (TIDieR) checklist was used to provide a comprehensive description of the AMPLIFY intervention, consistent with CONSORT recommendations., Results: A social cognitive theory web-based intervention founded on the core components of efficacious print and in-person interventions was conceptualized and developed through an iterative collaboration involving cancer survivors, web design experts, and a multidisciplinary investigative team. The intervention includes the AMPLIFY website, text and/or email messaging, and a private Facebook group. The website consists of: (1) Sessions (weekly interactive e-learning tutorials); (2) My Progress (logging current behavior, receiving feedback, setting goals); (3) Tools (additional information and resources); (4) Support (social support resources, frequently asked questions); and (5) Home page. Algorithms were used to generate fresh content daily and weekly, tailor information, and personalize goal recommendations. An a priori rubric was used to facilitate intervention delivery as healthy eating only (24 weeks), exercise only (24 weeks), or both behaviors concurrently over 48 weeks., Conclusions: Our TIDieR-guided AMPLIFY description provides pragmatic information helpful for researchers designing multibehavior web-based interventions and enhances potential opportunities to improve such interventions., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

Disparities in physical activity (PA) exist in rural regions and prior research suggests environmental features and community resources likely contribute. It is important to identify the opportunities and barriers that influence activity to appropriately inform PA interventions in such areas. Thus, we assessed the built environment, programs and policies related to PA opportunity in six rural Alabama counties that were purposively selected to inform a PA randomized controlled trial. Assessments were conducted August 2020-May 2021 using the Rural Active Living Assessment. Town characteristics and recreational amenities were captured using the Town Wide Assessment (TWA). PA programs and policies were examined with the Program and Policy Assessment. Walkability was evaluated using the Street Segment Assessment (SSA). Using the scoring system (0-100), the overall TWA score was 49.67 (range: 22-73), indicating few schools within walking distance (≤5 miles of the town's center) and town-wide amenities (e.g., trails, water/recreational activities) for PA. The Program and Policy Assessment showed a paucity of programming and guidelines to support activity (overall average score of 24.67, [range: 22-73]). Only one county had a policy requiring walkways/bikeways in new public infrastructure projects. During assessment of 96 street segments, few pedestrian-friendly safety features [sidewalks (32%), crosswalks (19%), crossing signals (2%), and public lighting (21%)] were observed. Limited opportunities for PA (parks and playgrounds) were identified. Barriers such as few policies and safety features (crossing signals, speed bumps) were indicated as factors that should be addressed when developing PA interventions and informing future policy efforts., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Purpose: Relating dose-volume histogram (DVH) information to patient outcomes is critical for outcomes research in radiation oncology, but this is statistically challenging. We performed this focused review of DVH toxicity studies to characterize current statistical approaches and determine the need for updated reporting recommendations., Methods and Materials: We performed a focused MEDLINE search to identify studies published in 5 radiation oncology specialty journals that associated dosimetry with toxicity outcomes in humans receiving radiotherapy between 2015 and 2021. Elements abstracted from each manuscript included the study outcome, organs-at-risk (OARs) considered, DVH parameters analyzed, summary of the analytic approach, use of multivariable statistics, goodness-of-fit reporting, completeness of model reporting, assessment of multicollinearity, adjustment for multiple comparisons, and methods for dichotomizing variables. Each study was also assessed for sufficient reporting to allow for replication of results., Results: The MEDLINE search returned 2,300 studies for review and 325 met the inclusion criteria for the analysis. DVH variables were dichotomized using cut points in 154 (47.4%) studies. Logistic regression (55.4% of studies) was the most common statistical method used to relate DVH to toxicity outcomes, followed by Cox regression (20.6%) and linear regression (12.0%). Multivariable statistical tests were performed in 226 (69.5%) studies; of these, the possibility of multicollinearity was addressed in 47.8% and model goodness-of-fit were reported in 32.6%. The threshold for statistical significance was adjusted to account for multiple comparisons in 41 of 196 (17.1%) studies that included multiple statistical comparisons. Twenty-eight (8.6%) studies were classified as missing details necessary to reproduce the study results., Conclusions: Current practices of statistical reporting in DVH outcomes suggest that studies may be vulnerable to threats against internal and external validity. Recommendations for reporting are provided herein to guard against such threats and to promote cohesiveness among radiation oncology outcomes researchers., (© 2023. The Author(s).)

Breast cancer survivors with obesity have an increased risk of cancer recurrence, second malignancy, and comorbidities. Though physical activity (PA) interventions are needed, investigation of the relationships between obesity and factors influencing PA program aspects among cancer survivors remain understudied. Thus, we conducted a cross-sectional study examining associations amongst baseline body mass index (BMI), PA program preferences, PA, cardiorespiratory fitness, and related social cognitive theory variables (self-efficacy, exercise barriers interference, social support, positive and negative outcome expectations) from a randomized controlled PA trial with 320 post-treatment breast cancer survivors. BMI was significantly correlated with exercise barriers interference ( r = 0.131, p = 0.019). Higher BMI was significantly associated with preference to exercise at a facility ( p = 0.038), lower cardiorespiratory fitness ( p < 0.001), lower walking self-efficacy ( p < 0.001), and higher negative outcome expectations ( p = 0.024), independent of covariates (comorbidity score, Western Ontario and McMaster Universities osteoarthritis index score, income, race, education). Those with class I/II obesity reported a higher negative outcome expectations score compared with class III. Location, walking self-efficacy, barriers, negative outcome expectations, and fitness should be considered when designing future PA programs among breast cancer survivors with obesity.

(1) Background: A healthful diet, regular physical activity, and weight management are cornerstones for cancer prevention and control. Yet, adherence is low in cancer survivors and others, calling for innovative solutions. Daughters, dUdes, mothers, and othErs fighting cancer Together (DUET) is a 6-month, online, diet-and-exercise, weight-loss intervention to improve health behaviors and outcomes among cancer survivor-partner dyads. (2) Methods: DUET was tested in 56 dyads (survivors of obesity-related cancers and chosen partners) ( n = 112), both with overweight/obesity, sedentary behavior, and suboptimal diets. After baseline assessment, dyads were randomized to DUET intervention or waitlist control arms; data were collected at 3- and 6-months and analyzed using chi-square, t -tests, and mixed linear models (α < 0.05). (3) Results: Retention was 89% and 100% in waitlisted and intervention arms, respectively. Dyad weight loss (primary outcome) averaged -1.1 (waitlist) vs. -2.8 kg (intervention) ( p = 0.044/time-by-arm interaction p = 0.033). Caloric intake decreased significantly in DUET survivors versus controls ( p = 0.027). Evidence of benefit was observed for physical activity and function, blood glucose, and c-reactive protein. Dyadic terms were significant across outcomes, suggesting that the partner-based approach contributed to intervention-associated improvements. (4) Conclusions: DUET represents a pioneering effort in scalable, multi-behavior weight management interventions to promote cancer prevention and control, calling for studies that are larger in size, scope, and duration.

Objectives: This study aimed to evaluate both efficacy and safety of combination therapy with daptomycin plus ceftaroline (DAP/CPT) versus alternative therapy in the treatment of persistent methicillin-resistant Staphylococcus aureus bacteraemia (MRSAB)., Methods: This retrospective, single-centre study investigated adult patients who underwent a change in antibiotic therapy for persistent MRSAB. Daptomycin plus ceftaroline was compared with alternative therapy after initial treatment with vancomycin or DAP monotherapy was modified. The primary outcome was in-hospital mortality, and several secondary efficacy and safety outcomes were evaluated., Results: A total of 68 patients with persistent MRSAB had initial therapy switched to DAP/CPT (n = 43) or alternative therapy (n = 25). In-hospital mortality was similar with DAP/CPT versus alternative therapy (16.3% vs. 16%; P = 1.0). On average, the total duration of bacteraemia was numerically 1 day less in patients switched to DAP/CPT (11.4 days vs. 12.5 days; P = 0.5). Daptomycin plus ceftaroline was de-escalated in 81% of patients after receiving combination therapy for an average of 12.5 days. Secondary outcomes, including rates of adverse events and emergence of antimicrobial resistance, were similar between the two groups., Conclusions: Switching to DAP/CPT after approximately 1 week of persistent MRSA bacteraemia may result in similar clinical outcomes when compared with alternative therapy. Rates of adverse events and emergence of antimicrobial resistance were low without a statistically significant difference observed between DAP/CPT and alternative therapy. These findings, as well as the impact of earlier switch or prolonged treatment with the combination, require further investigation., (Copyright © 2023 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.)

Background: Classroom lighting, usually bright fluorescent light, can significantly influence the learning environment and emotions of students., Objective: To assess the emotional impact of classroom lighting on students during an academic year., Methods: This study used an ABAB withdrawal research design in the following manner: in phase A, the baseline condition, classroom lighting was provided by conventional overhead white fluorescent classroom lights; in phase B, the intervention condition, the conventional overhead white fluorescent classroom lights were covered with fabric filters (thin, translucent, creamy-colored plastic sheets) that were attached to the lighting fixture frame with magnetic discs. The filters produced softer light in the classroom than the fluorescent lights. Each phase lasted for at least 2 weeks. During each phase, students rated 18 pairs of words from the Mehrabian and Russell pleasure, arousal, and dominance semantic differential scale at least four times to assess the emotional impact of the lighting conditions., Results: For all three emotional behaviors, the mean score of the filtered fluorescent light phase was significantly greater than the mean score of the baseline unfiltered fluorescent lighting phase, indicating more positive emotional responses. Students also noted they experienced fewer headaches and found it easier to see the whiteboard at the front of the classroom when the light filters were in place., Conclusion: The light filters exerted a positive impact on the students' emotions. Students preferred the filtered lighting to fluorescent lighting. This study supports the installation of filters over fluorescent lights in a college classroom., Competing Interests: None.

Background: Capsule endoscopy (CE) is an emerging tool in the diagnosis and management of occult bleeding and overt obscure gastrointestinal bleeding (OOGIB). Maximizing the efficiency of CE can lead to rapid bleeding localization and shorter time to therapy. We investigated whether a trained registered nurse (RN) can accurately interpret bleeding by observing the CE findings in real time by measuring inter-observer agreement between RN and physician interpretation., Methods: We conducted a prospective study of patients admitted for OOGIB who underwent live-view capsule endoscopy (LVCE) between December 2016 and November 2017. A matched control group who underwent standard CE was obtained through retrospective review. An RN received a 2-day training program for CE interpretation. RN bedside interpretation for bleeding was followed by interpretation by 2 gastrointestinal physicians blinded to LVCE findings. Outcomes were compared between groups using t-tests and χ2 tests. Cohen's kappa measured the agreement between the physicians and the RN., Results: Ten subjects were in the LVCE group, and 12 subjects were in the standard-of-care group. The agreement between the physicians and the RN was 9/10 (90%), with a kappa of 0.73 (95% CI: 0.26-1.00; p = 0.016). Patients in the LVCE group had shorter duration to physician interpretation (0.6 vs. 0.7 days [p = 0.50]), shorter duration to endoscopy (1.8 days vs. 3 days [p = 0.240]), and shorter length of stay (8.1 vs. 11.4 days [p = 0.26]) compared to the standard-of-care group., Conclusion: This study utilizing an RN for LVCE interpretation found inter-observer agreement between RN and physician findings. Larger studies are needed to assess whether this RN-physician team approach can translate to improved outcomes., (© 2022 S. Karger AG, Basel.)

Purpose: Moderate-to-vigorous physical activity (MVPA) can improve the quality of life (QoL) for breast cancer survivors (BCS), yet, most do not achieve 150 + weekly minutes of MVPA. This study investigated moderators of response to a physical activity (PA) behavior change intervention for BCS., Methods: BCS (N = 222) were randomized to the 3-month intervention (BEAT Cancer) or usual care. Measurements occurred at baseline, post-intervention, and 3 months post-intervention. Measures included accelerometry, self-reported MVPA, and Functional Assessment of Cancer Therapy (FACT-General, FACT-Breast, physical well-being (PWB), social well-being (SWB), emotional well-being (EWB), functional well-being (FWB), additional concerns (AC), and Trial Outcome Index (TOI))., Results: Adjusted linear mixed-model analyses indicated individuals ≤ 24 months post-diagnosis and who were single reported smaller increases in weekly self-reported MVPA than those > 24 months (44.07 vs 111.93) and partnered (- 16.24 vs. 49.16 min), all p < 0.05. As for QoL, participants < 12 months post-diagnosis who received chemotherapy experienced smaller improvements than those ≥ 12 months in FACT-General, FACT-Breast, PWB, and SWB scores. Survivors with a history of chemotherapy had smaller improvements in FACT-General, FACT-Breast, PWB, SWB, TOI, and AC scores, all p < 0.05., Conclusion: These findings indicate that being < 2 years post-diagnosis, single, and prior chemotherapy may limit MVPA and QOL responses to a PA intervention. Further studies are needed to determine if and/or what additional PA supports and resources these subgroups of BCS might find beneficial and effective., Trial Registration: ClinicalTrials.gov number: NCT00929617., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: Levasseur-Merrill retractor (LMR) utilization during the intraoral vertical ramus osteotomy (IVRO) helps initiate the osteotomy approximately 7 mm from the posterior border of the mandible, preventing damage to the inferior alveolar nerve. The purpose of this in vivo study is to evaluate the IVRO placement and the risk of neurosensory deficit (NSD) while using the LMR., Methods: This prospective case series was conducted at a single tertiary care center. Medical records were reviewed for medical and demographic information. Inclusion criteria were as follows: underwent the IVRO procedure by a single provider from June 2020 to June 2022 and postoperative cone beam computed tomography images. Exclusion criteria were as follows: age less than 16 years, previous mandibular osteotomies, inadequate clinical documentation, or follow-up. The primary outcome variables included the proximal segment width and proximity of the IVRO to the inferior alveolar foramen. The secondary outcome variable was NSD as measured subjectively by 2-point discrimination, sharp versus dull touch, and light touch with von Frey filaments., Results: The 26 subjects (42 operated sides) were 96% female, with an average age of 30.1 years (range 17-54 years). The mean proximal segment width was 10.3 ± 1.7 mm (95% confidence interval: 9.77, 10.83). The mean distance from the posterior border of the inferior alveolar foramen (IAF) to the osteotomy was -0.89 ± 1.7 mm (95% confidence interval: -1.43, -0.35), with negative numbers indicating violation of the IAF. IAF and full bony canal violation occurred in 61.9% and 4.8% of operated sides, respectively. NSD at 6 months postoperatively occurred in the 2 sides that experienced full bony canal violation., Conclusions: The LMR did not consistently guide the IVRO position within 7 mm from the posterior border of the mandible as previously thought and allows for frequent violation of the IAF. Long-term NSD of the inferior alveolar nerve was infrequent and correlated with violation of the full bony canal., (Copyright © 2022. Published by Elsevier Inc.)

Background: Accelerated functional decline is a concern among older cancer survivors that threatens independence and quality of life. Pilot studies suggest that vegetable gardening interventions ameliorate functional decline through improved diet and physical activity., Objective: The aim of this article was to describe the rationale, recruitment challenges, and enrollment for the Harvest for Health randomized controlled trial (RCT), which will test the impact of a home-based, vegetable gardening intervention on vegetable and fruit consumption, physical activity, and physical functioning among older cancer survivors. Modifications made to the intervention and assessments to assure safety and continuity of the RCT throughout the COVID-19 pandemic also are reported., Design: Harvest for Health is a 2-year, 2-arm, single-blinded, wait-list controlled RCT with cross-over., Participants/setting: Medicare-eligible survivors of cancers with ≥60% 5-year survival were recruited across Alabama from October 1, 2016 to February 8, 2021., Intervention: Participants were randomly assigned to a wait-list control or a 1-year home-based gardening intervention and individually mentored by extension-certified master gardeners to cultivate spring, summer, and fall vegetable gardens., Main Outcome Measures: Although the RCT's primary end point was a composite measure of vegetable and fruit consumption, physical activity, and physical functioning, this article focuses on recruitment and modifications made to the intervention and assessments during COVID-19., Statistical Analyses Performed: χ 2 and t tests (α < .05) were used to compare enrolled vs unenrolled populations., Results: Older cancer survivors (n = 9,708) were contacted via mail and telephone; 1,460 indicated interest (15% response rate), 473 were screened eligible and consented, and 381 completed baseline assessments and were randomized. Enrollees did not differ from nonrespondents/refusals by race and ethnicity, or rural-urban status, but comprised significantly higher numbers of comparatively younger survivors, those who were female, and survivors of breast cancer (P < .001). Although COVID-19 delayed trial completion, protocol modifications overcame this barrier and study completion is anticipated by June 2022., Conclusions: This RCT will provide evidence on the effects of a mentored vegetable gardening program among older cancer survivors. If efficacious, Harvest for Health represents a novel, multifaceted approach to improve lifestyle behaviors and health outcomes among cancer survivors-one with capacity for sustainability and widespread dissemination., (Copyright © 2022 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.)

Background: The number of exercise trials examining cardiometabolic outcomes in spinal cord injury (SCI) is low, and prescribed exercise is often inconvenient for individuals with SCI to perform within their community. Individuals with SCI experience a myriad of barriers to exercise participation, which can include a lack of time, accessible or usable equipment and facilities, and transportation. Thus, it is imperative to identify effective modes of exercise that provide the greatest overall health benefits but do not require a significant time commitment. Low-volume high intensity interval training (HIIT) has demonstrated the same improvements in cardiometabolic health as moderate intensity exercise training (MIT), despite only requiring 20% of the total time commitment in adults without disabilities and more recently in individuals with SCI., Objectives: The primary purpose of this study is to integrate a 16 week home-based telehealth HIIT arm crank exercise training program in individuals with SCI and assess changes in cardiometabolic health., Methods: Men and women between the ages of 19 and 60 with a confirmed diagnosis of SCI between C7 and T12 will be recruited for this study. Participants will be randomized to 16 weeks of telehealth HIIT exercise two days per week or a no-exercise control group. Aerobic capacity, muscular strength, blood lipids, glucose tolerance, resting energy expenditure, blood pressure, and body composition will be assessed at baseline and 16 weeks post-training., Discussion: Inactivity associated with SCI leads to chronic cardiometabolic health conditions. The majority of exercise interventions to date show that exercise is capable of increasing physical function, aerobic capacity, and muscle mass, and strength. Additionally, we have recently shown the ability of HIIT to improve blood lipid and glucose concentrations. Advances in telehealth exercise approaches have improved the capability to prescribe home-based exercise programs. Therefore, we hypothesize that the utilization of a home-based telehealth HIIT program will improve cardiometabolic health markers, yield high adherence (> 75%), and will be more enjoyable in individuals with SCI., Trial Registration: Telehealth High-Intensity Interval Exercise and Cardiometabolic Health in Spinal Cord Injury NCT04940598., (© 2022. The Author(s).)

Background: African American or Black young men who have sex with men (BYMSM) are at a disproportionate risk for contracting HIV and have high rates of undiagnosed, and therefore untreated, HIV infection. In the southern United States, BYMSM face region-specific hurdles to HIV prevention, such as limited access to care and high levels of racism and intersectional stigma, necessitating HIV testing and pre-exposure prophylaxis interventions that address sociocultural and structural barriers while motivating BYMSM to engage in prevention. Brothers Saving Brothers (BSB) is a motivational interviewing behavioral intervention that successfully and simultaneously increased community-based HIV testing and prevention counseling and education among BYMSM in the midwestern United States., Objective: The aim of this protocol is to detail the process for the adaption of the BSB intervention for midwestern BYMSM to the Kings intervention for southern BYMSM. During the adaptation process, the intervention will be modernized to include rapid HIV testing, as opposed to HIV testing that requires BYMSM to return for test results, pre-exposure prophylaxis, and the provision of structural supports, and for relevance in the southern United States., Methods: Aim 1 is to gather qualitative data through focus groups and in-depth interviews with BYMSM aged 18 to 29 years in Alabama and in-depth interviews with prevention and outreach workers who routinely work with BYMSM in Alabama. NVivo qualitative software (QSR International) will be used for the coding and analysis of the transcripts via a thematic analysis approach. For aim 2, intervention mapping will guide the adaptation process, intervention content, components, and design. Both aims 1 and 2 will leverage the Exploration, Preparation, Implementation, Sustainment implementation science framework, with emphasis on the exploration and preparation phases of this model. By applying these frameworks, the original midwestern BSB intervention will be scientifically adapted to the southern BYMSM Kings intervention., Results: This study is ongoing as of 2022 and is expected to conclude in 2024, with aims 1 and 2 being completed in 2023. Qualitative data will offer insight into the current real-world experiences and preferences of BYMSM in Alabama. Feedback will be collected through the adaptation process to inform intervention refinement. Institutional review board approvals have been received., Conclusions: The findings will inform next steps, that is, testing the Kings intervention for feasibility, acceptability, and preliminary effectiveness in a pilot hybrid type 1 effective-implementation randomized controlled trial. The study results will provide insights about important considerations for HIV prevention among BYMSM in the southern United States., Trial Registration: ClinicalTrials.gov NCT03680729; https://clinicaltrials.gov/ct2/show/NCT03680729., International Registered Report Identifier (irrid): PRR1-10.2196/36655., (©Henna Budhwani, B Matthew Kiszla, Angulique Y Outlaw, Robert A Oster, Michael J Mugavero, Mallory O Johnson, Lisa B Hightow-Weidman, Sylvie Naar, Janet M Turan. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 13.07.2022.)

Purpose: Primary Central Nervous System Lymphoma (PCNSL) is an aggressive tumor that is confined to the CNS. Although the provision of high-dose methotrexate (HD-MTX) has remarkably improved outcomes in PCNSL patients, the optimal treatment regimens and standard MTX dose for induction therapy have been largely controversial. Herein, we sought to explore the impact of adjuvant rituximab and different dosages of induction HD-MTX on survival outcomes of immunocompetent patients with PCNSL., Methods: In this study, we examined patients with PCNSL treated at a single NCI-designated comprehensive cancer center to evaluate their survival outcomes. We conducted a retrospective analysis of 51 immunocompetent patients with PCNSL who received their induction chemotherapy at the University of Alabama at Birmingham (UAB) between 2001 and 2019. Only adult patients with a confirmed diagnosis of PCNSL who had either HD-MTX alone or in combination with rituximab were included. Patients' demographics, clinical characteristics, and survival data were collected and analyzed., Results: There is no significant difference in survival among patients who received MTX alone versus MTX plus rituximab (HR = 0.996 (95% CI: 0.398-2.493), p = 0.994). Lower doses of MTX were associated with worse survival outcomes (HR = 0.680 (95% CI: 0.530-0.872), p = 0.002); however, this difference in survival was not significant when adjusted to age (HR = 0.797 (95% CI: 0.584-1.088), p = 0.153)., Conclusion: Our experience challenges the role of rituximab in PCNSL during induction therapy. Our study also highlights the shorter survival in elderly patients with PCNSL which can be related, to some extent, to the relatively lower doses of HD-MTX. There is an unmet need to establish a consensus on the most effective upfront regimen in PCNSL through prospective studies., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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., (© 2022. The Author(s).)

(1) Background: Anthropometric and physical performance testing is commonly done in lifestyle research and is traditionally performed in-person. To expand the scalability of lifestyle interventions among cancer survivors, in-person assessments were adapted to remote means and evaluated for feasibility, safety, validity, and reliability. (2) Methods: Cancer survivors and supportive partners were approached to participate in three anthropometric and physical performance testing sessions (two remote/one in-person). Correlations, concordance, and differences between testing modes were evaluated. (3) Results: 110-of-112 individuals approached for testing participated (98% uptake); the sample was 78% female, 64% non-Hispanic White, of mean age 58 years and body mass index = 32.4 kg/m 2 . ICCs for remote assessments ranged from moderate (8' walk = 0.47), to strong (8' get-up-and-go = 0.74), to very strong (30 s chair stand = 0.80; sit-and-reach = 0.86; 2 min step test = 0.87; back scratch = 0.90; weight = 0.93; waist circumference = 0.98) ( p -values < 0.001). Perfect concordance (100%) was found for side-by-side and semi-tandem balance, and 87.5-90.3% for tandem balance. No significant differences between remote and in-person assessments were found for weight, 8' walk, and 8' get-up-and-go. No adverse events occurred and 75% indicated no preference or preferred virtual testing to in-person. (4) Conclusions: Remote anthropometric and physical performance assessments are reliable, valid, acceptable, and safe among cancer survivors and supportive partners.

Background During the COVID-19 pandemic, in-person research assessments needed to be adapted to ensure safety of participants and staff. Participants' willingness to participate in research activities, how to prepare assessors to ensure data integrity, and the feasibility of modified protocols, were unknown. Within the AMPLIFI randomized clinical trial (RCT) for cancer survivors, we elicited participants' preferences and willingness to participate in Clinic, Home, or Virtual assessments, prepared assessors for, and implemented virtual assessments. Methods 1) We conducted phone surveys of potential AMPLIFI participants; 2) Based on survey results, we modified assessments from in-person to virtual visits (VV) by videoconference. Assessors were trained and certified, i.e., assessors recorded 3 assessments that were reviewed and scored by 2 investigators. The modified protocol was proposed to 62 participants: we report numbers of those who agreed to attend VV. Results 1) Survey results: Among 74 survey respondents, 44.6% preferred, 75.7% were willing to attend Clinic Visits; 32.4% preferred, 83.8% were willing to do VV; 23% preferred, 77% were willing to do Home Visits. Survivors 70+ were less likely than 50-69 years old to be willing to do VV: no other differences were noted by gender, race, rural status or education. 2) Assessment uptake: 66.1% agreed to attend VV, and of them 75.6% completed them. Conclusion Diverse research participants adapted to protocols that prioritize their safety, although older participants may be reluctant to do virtual assessments. Virtual assessments are feasible and research teams can rigorously prepare to collect quality data through them., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: With the increasing number of older cancer survivors, it is imperative to optimize the reach of interventions that promote healthy lifestyles. Web-based delivery holds promise for increasing the reach of such interventions with the rapid increase in internet use among older adults. However, few studies have explored the views of middle-aged and older cancer survivors on this approach and potential variations in these views by gender or rural and urban residence., Objective: The aim of this study was to explore the views of middle-aged and older cancer survivors regarding the features of web-based healthy lifestyle programs to inform the development of a web-based diet and exercise intervention., Methods: Using a qualitative descriptive approach, we conducted 10 focus groups with 57 cancer survivors recruited from hospital cancer registries in 1 southeastern US state. Data were analyzed using inductive thematic and content analyses with NVivo (version 12.5, QSR International)., Results: A total of 29 male and 28 female urban and rural dwelling Black and White survivors, with a mean age of 65 (SD 8.27) years, shared their views about a web-based healthy lifestyle program for cancer survivors. Five themes emerged related to program content, design, delivery, participation, technology training, and receiving feedback. Cancer survivors felt that web-based healthy lifestyle programs for cancer survivors must deliver credible, high-quality, and individually tailored information, as recommended by health care professionals or content experts. Urban survivors were more concerned about information reliability, whereas women were more likely to trust physicians' recommendations. Male and rural survivors wanted information to be tailored to the cancer type and age group. Privacy, usability, interaction frequency, and session length were important factors for engaging cancer survivors with a web-based program. Female and rural participants liked the interactive nature and visual appeal of the e-learning sessions. Learning from experts, an attractive design, flexible schedule, and opportunity to interact with other cancer survivors in Facebook closed groups emerged as factors promoting program participation. Low computer literacy, lack of experience with web program features, and concerns about Facebook group privacy were important concerns influencing cancer survivors' potential participation. Participants noted the importance of technology training, preferring individualized help to standardized computer classes. More rural cancer survivors acknowledged the need to learn how to use computers. The receipt of regular feedback about progress was noted as encouragement toward goal achievement, whereas women were particularly interested in receiving immediate feedback to stay motivated., Conclusions: Important considerations for designing web-based healthy lifestyle interventions for middle-aged and older cancer survivors include program quality, participants' privacy, ease of use, attractive design, and the prominent role of health care providers and content experts. Cancer survivors' preferences based on gender and residence should be considered to promote program participation., (©Nataliya V Ivankova, Laura Q Rogers, Ivan I Herbey, Michelle Y Martin, Maria Pisu, Dorothy Pekmezi, Lieu Thompson, Yu-Mei M Schoenberger-Godwin, Robert A Oster, Kevin Fontaine, Jami L Anderson, Kelly Kenzik, David Farrell, Wendy Demark-Wahnefried. Originally published in JMIR Cancer (https://cancer.jmir.org), 06.10.2021.)

Scalable, effective interventions are needed to address poor diet, insufficient physical activity, and obesity amongst rising numbers of cancer survivors. Interventions targeting survivors and their friends and family may promote both tertiary and primary prevention. The design, rationale, and enrollment of an ongoing randomized controlled trial (RCT) (NCT04132219) to test a web-based lifestyle intervention for cancer survivors and their supportive partners are described, along with the characteristics of the sample recruited. This two-arm, single-blinded RCT randomly assigns 56 dyads (cancer survivor and partner, both with obesity, poor diets, and physical inactivity) to the six-month DUET intervention vs. wait-list control. Intervention delivery and assessment are remotely performed with 0-6 month, between-arm tests comparing body weight status (primary outcome), and secondary outcomes (waist circumference, health indices, and biomarkers of glucose homeostasis, lipid regulation and inflammation). Despite COVID-19, targeted accrual was achieved within 9 months. Not having Internet access was a rare exclusion (<2%). Inability to identify a support partner precluded enrollment of 42% of interested/eligible survivors. The enrolled sample is diverse: ages 23-81 and 38% racial/ethnic minorities. Results support the accessibility and appeal of web-based lifestyle interventions for cancer survivors, though some cancer survivors struggled to enlist support partners and may require alternative strategies.

Purpose: Implementing efficacious physical activity interventions in real-world rural settings is needed because rural cancer survivors are more physically inactive and experience poorer health. To address this gap, this study evaluated effectiveness of an evidenced-based physical activity program (Better Exercise Adherence after Treatment for Cancer [BEAT Cancer]) for rural women cancer survivors when implemented by community-based, non-research staff., Methods: 16 rural women cancer survivors received BEAT Cancer implemented by a rural, community organization and non-research staff; physical activity, patient-reported outcomes, and social cognitive constructs were measured at baseline and post-program. Cancer survivors and interventionists completed program evaluations post-program., Results: Cancer survivor mean age was 58±12 years; 62% were White. Mean months since diagnosis was 54±72; 69% had breast cancer. Significant improvements from pre- to post-program occurred for self-report weekly minutes of moderate-to-vigorous physical activity (mean change [ M ] = 146±186, p = 0.009), anxiety ( M = -1.3±1.8, p = 0.016), depression ( M = -2.1±2.0, p = 0.001), self-efficacy ( M = 20.9±30.5, p = 0.019), barriers interference ( M = -15.0±14.1, p = 0.001), and social support ( M = 5.0±7.4, p = 0.02). Cancer survivors ranked the program highly, identified strategies that were helpful (e.g., group activities, personalized exercise plan, etc.), and suggested additional implementation strategies (e.g., guide for home-based phase, etc.). Interventionists identified strategies (e.g., logistics, staff training and certification, cost, etc.) for enhancing organizational readiness for program delivery., Conclusion: Evidence-based physical activity programs can be effective when implemented by non-research staff in rural settings. Further research testing strategies that improve implementation is needed., Practical Implications: Effectiveness and identified strategies supporting delivery when implemented by a rural organization can improve physical activity promotion for rural, at-risk populations., Competing Interests: Conflicts of Interest: All authors declare that no conflicts of interest exist. The views of this paper do not constitute endorsement by the ACSM.

Background: Optimal treatment of nonoperative patients with large, node-negative non-small cell lung cancer (NSCLC) is poorly defined. Current NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) recommend definitive radiotherapy (RT) with or without sequential chemotherapy and do not include concurrent chemoradiotherapy (chemoRT) as a treatment option. In this study, we identified factors that predict nonadherence to NCCN Guidelines., Patients and Methods: Patients who received definitive RT for nonmetastatic, node-negative NSCLC with tumor size of 5 to 7 cm were identified in the National Cancer Database from 2004 through 2016. Patients were evaluated by RT type (stereotactic body RT [SBRT], hypofractionated RT [HFRT], or conventionally fractionated RT [CFRT]) and chemotherapy use (none, sequential, or concurrent with RT). Patients were classified as receiving NCCN-adherent (RT with or without sequential chemotherapy) or NCCN-nonadherent (concurrent chemoRT) treatment. Demographic and clinical factors were assessed with logistic regression modeling. Overall survival was evaluated with Kaplan-Meier, log-rank, and univariable/multivariable Cox proportional hazards regression analyses., Results: Among 2,020 patients in our cohort, 32% received NCCN-nonadherent concurrent chemoRT, whereas others received NCCN-adherent RT alone (51%) or sequential RT and chemotherapy (17%). CFRT was most widely used (64% CFRT vs 22% SBRT vs 14% HFRT). Multivariable analysis revealed multiple factors to be associated with NCCN-nonadherent chemoRT: age ≤70 versus >70 years (odds ratio [OR] , 2.72; P<.001), treatment at a nonacademic facility (OR, 1.65; P<.001), and tumor size 6 to 7 cm versus 5 to 6 cm (OR, 1.27; P=.026). Survival was similar between the NCCN-nonadherent chemoRT and NCCN-adherent groups (hazard ratio, 1.00; P=.992) in multivariable analysis., Conclusions: A substantial proportion of inoperable patients with large, node-negative NSCLC are not treated according to NCCN Guidelines and receive concurrent chemoRT. Younger patients with larger tumors receiving treatment at nonacademic medical centers were more likely to receive NCCN-nonadherent therapy, but adherence to NCCN Guidelines was not associated with differences in overall survival.

Introduction: The incidence of pediatric urolithiasis has been increasing over the years; however, the etiology of this increase is not well understood. Age, body mass index, and gender have been examined as possible risk factors for stone disease, but with inconsistent and variable associations., Objective: We aim to investigate the urine chemistry factors, as assessed by 24-h urinary parameters, in pediatric stone formers at a large volume tertiary referral center in the highest areas in the United States, the Southeast, based on age, body mass index, and gender., Study Design: We retrospectively reviewed all pediatric stone formers who completed a 24-h study between 2005 and 2016. Patients were stratified by age (3-10 versus 11-18 years of age), overweight status (above versus below the 85th percentile for body mass index), and gender (male versus female) (Summary Figure). Statistical analysis included analysis of variance and logistic regression., Results: 243 patients were included in our analysis. Patients in the first decade of life were found to have greater numbers of urinary risk factors than those in the second decade. Non-overweight patients were more likely to have hyperoxaluria and hyperuricosuria, while overweight patients were more likely to have hypocitraturia. Female patients were more likely to have higher hyperoxaluria, while male patients were more likely to have hypercalciuria., Discussion: In contrast to prior publications, obesity is not linked to increased risk of urolithiasis with non-overweight individuals having a greater number of risk factors than the overweight cohort. Despite stone disease being more prevalent in adolescents, the greatest number of risk factors were present in the first decade of life. Lastly, female children had more urinary risk factors than males. Further understanding of the underlying causes of stone disease in various pediatric populations is warranted., Conclusion: While more urinary risk factors were identified in younger, non-overweight, and female patients, there remains no consensus on the urinary risk factors for pediatric urolithiasis. Further study is needed to elucidate the risk factors and pathophysiology of pediatric stone disease., Competing Interests: Conflict of interest The authors declare that they have no conflict of interest., (Published by Elsevier Ltd.)

Purpose: To qualitatively explore exercise barriers and facilitators experienced by rural female cancer survivors from the program interventionist and recipient perspective for the purpose of enhancing exercise program implementation and uptake in rural settings., Methods: A descriptive qualitative study design was utilized. Focus groups were conducted prior to implementation of an evidence-based exercise program by a rural non-research cancer clinical site. Nineteen rural female cancer survivors (mean age = 61.7 ± 10.9 years) and 11 potential interventionists (mean age = 42.3 ± 15.3 years) completed focus groups (stratified by participant role). Focus groups were audio recorded, transcribed, coded, and analyzed using inductive thematic analysis with NVivo 11., Results: Cancer survivors identified 12 barrier themes (cancer specific adverse effects, lack of support, lack of knowledge, perceived negative aspects of exercise, cost, lack of resources, motivation, inconvenience, lack of program flexibility, time, weather, safety) and eight facilitator themes (knowledge, ease of access, resources, awareness, cost, options, organized, fun) related to exercise. Interventionists identified seven barrier themes (cost, transportation, lack of cancer survivor and interventionist knowledge, fear, motivation, lack of support, lack of resources) and four facilitator themes (resources, support, knowledge, motivation). Narratives revealed differing role-specific perspectives on shared themes between survivors and interventionists as well as potential implementation strategies for enhancing exercise participation and exercise program uptake among rural female cancer survivors., Conclusion: Exploring multi-level stakeholder perspectives on cancer survivors' exercise needs and related strategies yields important information for organizations to consider when implementing exercise programs in rural contexts.

Rigorous scientific review of research protocols is critical to making funding decisions, and to the protection of both human and non-human research participants. Given the increasing complexity of research designs and data analysis methods, quantitative experts, such as biostatisticians, play an essential role in evaluating the rigor and reproducibility of proposed methods. However, there is a common misconception that a statistician's input is relevant only to sample size/power and statistical analysis sections of a protocol. The comprehensive nature of a biostatistical review coupled with limited guidance on key components of protocol review motived this work. Members of the Biostatistics, Epidemiology, and Research Design Special Interest Group of the Association for Clinical and Translational Science used a consensus approach to identify the elements of research protocols that a biostatistician should consider in a review, and provide specific guidance on how each element should be reviewed. We present the resulting review framework as an educational tool and guideline for biostatisticians navigating review boards and panels. We briefly describe the approach to developing the framework, and we provide a comprehensive checklist and guidance on review of each protocol element. We posit that the biostatistical reviewer, through their breadth of engagement across multiple disciplines and experience with a range of research designs, can and should contribute significantly beyond review of the statistical analysis plan and sample size justification. Through careful scientific review, we hope to prevent excess resource expenditure and risk to humans and animals on poorly planned studies., Competing Interests: The authors have no conflicts of interest to declare., (© The Association for Clinical and Translational Science 2021.)