Evaluating the scaling up of an effective implementation intervention (PACE) to increase the delivery of a mandatory physical activity policy in primary schools.

BACKGROUND: Physically Active Children in Education (PACE) is an effective implementation intervention for increasing the number of minutes classroom teachers schedule physical activity each week. To date, evaluations of PACE have included a smaller number of schools from only one region in New South Wales Australia. If PACE is to have population-wide benefits we must be able to deliver this support to a larger number of schools across multiple regions. This study aimed to evaluate the scale-up of PACE. METHODS: An uncontrolled before and after study, with 100 schools from three regions was conducted. Participating schools received PACE for approximately 12 months. We assessed the following outcomes: delivery of the evidence-based intervention (EBI) (i.e. minutes of physical activity scheduled by classroom teachers per week); delivery of the implementation strategies (i.e. reach, dose delivered, adherence and indicators of sustainability); and key determinants of implementation (i.e. acceptability of strategies and cost). Data were collected via project officer records, and principal and teacher surveys. Linear mixed models were used to assess EBI delivery by evaluating the difference in the mean minutes teachers scheduled physical activity per week from baseline to follow-up. Descriptive data were used to assess delivery of the implementation strategies and their perceived acceptability (i.e. PACE). A prospective, trial-based economic evaluation was used to assess cost. RESULTS: Delivery of the EBI was successful: teachers increas their average minutes of total physical activity scheduled across the school week by 26.8 min (95% CI: 21.2, 32.4, p < 0.001) after receiving PACE. Indicators for delivery of implementation strategies were high: 90% of consenting schools received all strategies and components (reach); 100% of strategies were delivered by the provider (dose); >50% of schools adhered to the majority of strategies (11 of the 14 components); and acceptability was > 50% agreement for all strategies. The incremental cost per additional minute of physical activity scheduled per week was $27 per school (Uncertainty Interval $24, $31). CONCLUSIONS: PACE can be successfully delivered across multiple regions and to a large number of schools. Given the ongoing and scalable benefits of PACE, it is important that we continue to extend and improve this program while considering ways to reduce the associated cost.

Derivation and external validation of a risk score for clinically important declines in health and function among two longitudinal cohorts of women in the mid-life.

OBJECTIVES: Women in mid-life often develop chronic conditions and experience declines in physical health and function. Identifying factors associated with declines provides opportunity for targeted interventions. We derived and externally validated a risk score for clinically important declines over 10 years among women ages 55-65 using the Physical Component Summary Score (PCS) of the SF-36. DESIGN: Derivation and validation of a risk score. SETTING: Two longitudinal cohorts from sites in the USA were used. PARTICIPANTS: Women from the Study of Women's Health Across the Nation (SWAN) and women from the Women's Health Initiative (WHI) Observational Study and/or clinical trials. OUTCOME MEASURES: A clinically important decline over 10 years among women ages 55-65 using the PCS of the SF-36 predictors was measured at the beginning of the 10 years of follow-up. RESULTS: Seven factors-lower educational attainment, smoking, higher body mass index, history of cardiovascular disease, history of osteoarthritis, depressive symptoms and baseline PCS level-were found to be significant predictors of PCS decline among women in SWAN with an area under the curve (AUC)=0.71 and a Brier Score=0.14. The same factors were associated with a decline in PCS in WHI with an AUC=0.64 and a Brier Score=0.18. Regression coefficients from the SWAN analysis were used to estimate risk scores for PCS decline in both cohorts. Using a threshold of a 30% probability of a significant decline, the risk score created a binary test with a specificity between 89%-93% and an accuracy of 73%-79%. CONCLUSIONS: Seven clinical variables were used to create a valid risk score for PCS declines that was replicated in an external cohort. The risk score provides a method for identifying women at high risk for a significant mid-life PCS decline.

Resiliency Among Women's Health Initiative Women Aged 80 and Older by Race, Ethnicity, and Neighborhood Socioeconomic Status.

OBJECTIVES: A comprehensive examination of resilience by race, ethnicity, and neighborhood socioeconomic status (NSES) among women aged ≥80 is needed, given the aging of the U.S. population, increasing longevity, and growing racial and ethnic diversity. METHODS: Participants were women aged ≥80 enrolled in the Women's Health Initiative. Resilience was assessed with a modified version of the Brief Resilience Scale. Descriptive statistics and multiple linear regression examined the association of demographic, health, and psychosocial variables with resilience by race, ethnicity, and NSES. RESULTS: Participants (n = 29,367, median age = 84.3) were White (91.4%), Black (3.7%), Hispanic (1.9%), and Asian (1.7%) women. There were no significant differences by race and ethnicity on mean resiliency scores (p = .06). Significant differences by NSES were observed regarding mean resiliency scores between those with low NSES (3.94 ± 0.83, out of 5) and high NSES (4.00 ± 0.81). Older age, higher education, higher self-rated health, lower stress, and living alone were significant positive correlates of resilience in the sample. Social support was correlated with resilience among White, Black, and Asian women, but not for Hispanic women. Depression was a significant correlate of lower resilience, except among Asian women. Living alone, smoking, and spirituality were significantly associated with higher resilience among women with moderate NSES. DISCUSSION: Multiple factors were associated with resilience among women aged ≥80 in the Women's Health Initiative. Despite some differing correlates of resilience by race, ethnicity, and NSES, there were many similarities. These results may aid in the design of resilience interventions for the growing, increasingly diverse population of older women.

Transitions to smokeless tobacco use among adult cigarette smokers in the Population Assessment of Tobacco and Health (PATH) Study, Waves 3-5 (2015-2019).

OBJECTIVE: Examine patterns of dual use of cigarettes and smokeless tobacco and complete switching over time among adult current cigarette smokers using data from the Population Assessment of Tobacco and Health Study Wave 3 (2015-2016), Wave 4 (2016-2018) and Wave 5 (2018-2019). METHODS: We examined four tobacco use states among 6834 exclusive smokers and 372 dual users at Wave 3 with two waves of follow-up data: exclusive cigarette use, exclusive smokeless tobacco use, dual use and use of neither product. RESULTS: Among exclusive smokers at Wave 3, only 1.6% (95% CI: 1.3% to 2.1%) transitioned to dual use at Wave 4, and 0.1% (95% CI: 0.07% to 0.2%) switched to exclusive smokeless tobacco use. Among exclusive smokers who switched to dual use, 53.1% (95% CI: 40.9% to 64.9%) returned to exclusive cigarette smoking, 34.3% (95% CI: 23.8% to 46.6%) maintained dual use and 12.6% (95% CI: 7.0% to 21.7%) did not smoke cigarettes after an additional wave of follow-up. Dual users at Wave 3 were likely to maintain their dual use status at Wave 4, 51.2% (95% CI: 46.1% to 56.3%) and Wave 5, 47.9% (95% CI: 40.1% to 55.8%). CONCLUSIONS: Very few cigarette smokers transition to smokeless tobacco use, and among those who do, dual use is more common than exclusive smokeless tobacco use. Further, the majority of exclusive cigarette smokers who transition to dual use at Wave 4 continue smoking cigarettes at Wave 5, either as dual users or as exclusive smokers.

Characteristics and Patterns of Cigarette Smoking and Vaping By Past-Year Smokers Who Reported Using Electronic Nicotine Delivery System to Help Quit Smoking in the Past Year: Findings From the 2018-2019 Tobacco Use Supplement to the Current Population Survey.

INTRODUCTION: Cigarette smoking has declined, while electronic nicotine delivery system (ENDS) use has increased in the United States. Understanding the role of ENDS in adult smoking quit attempts and cessation is important for estimating their population health impact. AIMS AND METHODS: We used data from 2018 to 2019 tobacco use supplement to the current population survey to examine demographic characteristics and ENDS use patterns among adult ENDS users who reported quitting smoking in the past year by trying to switch to ENDS ("switchers") and smokers who did or did not make a quit attempt in the past year. χ2 tests of proportions and t-tests were used to compare characteristics between groups. RESULTS: In 2018-2019, about three-quarters of switchers reported daily use of ENDS compared to only one-third of dual users with a recent quit attempt by trying to switch to ENDS. Compared to dual users who made a quit attempt by trying to switch to ENDS, switchers were more likely to use menthol/mint-flavored ENDS exclusively (5.6% vs. 13.1%; p = .004) but less likely to use tobacco-flavored ENDS exclusively (21.2% vs. 13.7%; p = .01). CONCLUSIONS: ENDS users who quit smoking in the past year and reported trying to quit by switching to ENDS were more likely to use menthol/mint flavors exclusively and use ENDS daily compared to dual users who made a quit attempt by trying to switch to ENDS. Longer-term prospective data may better clarify the role of ENDS in smoking quit attempts and cessation. IMPLICATIONS: This study provides information on patterns of ENDS use in former smokers and current smokers who tried to quit smoking by switching to ENDS in a national sample of U.S. adults. These results can inform policy actions concerning ENDS products.

The inexorable increase of biologic exposure in paediatric inflammatory bowel disease: a Scottish, population-based, longitudinal study.

BACKGROUND: The use of biologics in paediatric-onset inflammatory bowel disease (PIBD) is rapidly changing. AIMS: To identify the incidence and prevalence of biologic use within Scottish PIBD services, and to describe patient demographics and outcomes for those patients who required escalation of therapy beyond anti-tumour necrosis factor alpha (anti-TNFα) agents METHODS: We captured a nationwide cohort of prospectively identified patients less than 18 years of age with PIBD (A1 phenotype; diagnosed <17 years of age) within paediatric services over a 4.5-year period (1 January 2015-30 June 2019). All patients who received infliximab, adalimumab, vedolizumab or ustekinumab during the study period and/or received their first dose of these biologics were audited retrospectively. RESULTS: Scotland-wide PIBD-prevalence cases increased from 554 to 644 over the study period. A total of 495 incident new-start biological therapies were commenced on 403 PIBD patients: 295 infliximab (60%), 161 adalimumab (32%), 24 vedolizumab (5%) and 15 ustekunumab (3%). The proportion of new-start biologics changed with infliximab initiation rates decreasing (87%-54%) while adalimumab (13%-31%), vedolizumab (0%-9%) and ustekinumab (0%-6%) all increased. The incidence rate (first dose of new biologic not including biosimilar switch) increased from 6.9% to 8.1% over the study period and point prevalence rates (any biologic use) increased from 20.2% to 43.5% - an average annual percentage increase of 20%. Biosimilar penetration of new-start anti-TNFα agents increased from 3% to 91%. Demographics and outcomes of those patients receiving vedolizumab and ustekinumab were similar. CONCLUSIONS: Complete accrual of Scottish nationwide biologic usage within paediatric services demonstrates a rapidly changing, inexorably increasing PIBD biologics landscape.

The conundrum of breast density; guidance for healthcare providers.

A finding of dense breasts on mammogram decreases the sensitivity of mammogram and increases a woman's risk of breast cancer. Supplemental screening can increase breast cancer detection in women with dense breasts, but caries a risk of increased false-positive test results. There are currently no clear guidelines for providers or patients on recommendations for supplemental screening after a mammogram finding of heterogeneously or extremely dense breasts on mammography. In addition, there is currently great variation in communication and management of breast density amongst physicians and other licensed providers. Women at higher risk for developing breast cancer would benefit most from supplemental screening. Standardizing recommendations and implementation of risk-based decision-making using a validated calculator would allow for earlier detection of breast cancer, clear guidance for providers, and ensure equitable care for patients.

Association of e-Cigarette Use With Discontinuation of Cigarette Smoking Among Adult Smokers Who Were Initially Never Planning to Quit.

Importance: Cigarette smokers not planning to quit are often overlooked in population studies evaluating the risk-benefit potential of electronic nicotine delivery products (e-cigarettes). Objective: To evaluate whether e-cigarette use is associated with discontinuing cigarette smoking among smokers who were initially never planning to quit. Design, Setting, and Participants: This cohort study used US nationally representative data from the longitudinal Population Assessment of Tobacco and Health Study (waves 2-5 conducted between October 2014 and November 2019), with participants evaluated in 3 pairs of interviews. Adult daily cigarette smokers initially not using e-cigarettes and with no plans to ever quit smoking for good (2489 observations from 1600 individuals) were included. Exposures: e-Cigarette use (ie, daily use, nondaily use, or no use) at follow-up interview among smokers not using e-cigarettes at baseline interview. Main Outcomes and Measures: The main outcomes were discontinuation of cigarette smoking (ie, no cigarette smoking) and discontinuation of daily cigarette smoking (ie, no daily cigarette smoking) at follow-up interview. Generalized estimating equations were used to evaluate the association between the exposure and each outcome, controlling for demographic characteristics and cigarettes smoked per day at baseline interview; all estimates were weighted. Results: The weighted population of adult daily cigarette smokers who were not using e-cigarettes and had no plans to ever quit smoking, based on data from 1600 participants, was 56.1% male (95% CI, 53.4%-58.7%), 10.1% Hispanic (95% CI, 8.2%-12.3%), 10.1% non-Hispanic Black (95% CI, 8.7%-11.7%), 75.6% non-Hispanic White (95% CI, 72.9%-78.2%), and 4.2% of other non-Hispanic race (95% CI, 3.3%-5.4%); 29.3% were aged 55 to 69 years (95% CI, 26.2%-32.6%), 8.9% were aged 70 years or older (95% CI, 6.8%-11.5%), 36.8% did not graduate from high school (95% CI, 34.1%-39.6%), 55.2% had an annual household income of less than $25 000 (95% CI, 52.3%-58.1%), 37.6% smoked 20 to 29 cigarettes per day (95% CI, 34.7%-40.6%), and 12.7% smoked 30 or more cigarettes per day (95% CI, 10.9%-14.7%). Overall, 6.2% of the population (95% CI, 5.0%-7.5%) discontinued cigarette smoking. Discontinuation rates were higher among those who used e-cigarettes daily (28.0%; 95% CI, 15.2%-45.9%) compared with not at all (5.8%; 95% CI, 4.7%-7.2%; adjusted odds ratio [aOR], 8.11; 95% CI, 3.14-20.97). Furthermore, 10.7% (95% CI, 9.1%-12.5%) discontinued daily cigarette smoking, with higher rates of discontinuation observed among those who used e-cigarettes daily (45.5%; 95% CI, 27.4%-64.9%) compared with not at all (9.9%; 95% CI, 8.2%-11.8%; aOR, 9.67; 95% CI, 4.02-23.25). Nondaily e-cigarette use was not associated with cigarette discontinuation (aOR, 0.53; 95% CI, 0.08-3.35) or daily cigarette discontinuation (aOR, 0.96; 95% CI, 0.44-2.09). Conclusions and Relevance: In this cohort study, daily e-cigarette use was associated with greater odds of cigarette discontinuation among smokers who initially had no plans to ever quit smoking. These findings support the consideration of smokers who are not planning to quit when evaluating the risk-benefit potential of e-cigarettes for smoking cessation in the population.

Genome-wide homozygosity and risk of four non-Hodgkin lymphoma subtypes.

AIM: Recessive genetic variation is thought to play a role in non-Hodgkin lymphoma (NHL) etiology. Runs of homozygosity (ROH), defined based on long, continuous segments of homozygous SNPs, can be used to estimate both measured and unmeasured recessive genetic variation. We sought to examine genome-wide homozygosity and NHL risk. METHODS: We used data from eight genome-wide association studies of four common NHL subtypes: 3061 chronic lymphocytic leukemia (CLL), 3814 diffuse large B-cell lymphoma (DLBCL), 2784 follicular lymphoma (FL), and 808 marginal zone lymphoma (MZL) cases, as well as 9374 controls. We examined the effect of homozygous variation on risk by: (1) estimating the fraction of the autosome containing runs of homozygosity (FROH); (2) calculating an inbreeding coefficient derived from the correlation among uniting gametes (F3); and (3) examining specific autosomal regions containing ROH. For each, we calculated beta coefficients and standard errors using logistic regression and combined estimates across studies using random-effects meta-analysis. RESULTS: We discovered positive associations between FROH and CLL (ß = 21.1, SE = 4.41, P = 1.6 × 10-6) and FL (ß = 11.4, SE = 5.82, P = 0.02) but not DLBCL (P = 1.0) or MZL (P = 0.91). For F3, we observed an association with CLL (ß = 27.5, SE = 6.51, P = 2.4 × 10-5). We did not find evidence of associations with specific ROH, suggesting that the associations observed with FROH and F3 for CLL and FL risk were not driven by a single region of homozygosity. CONCLUSION: Our findings support the role of recessive genetic variation in the etiology of CLL and FL; additional research is needed to identify the specific loci associated with NHL risk.

Blood n-3 fatty acid levels and total and cause-specific mortality from 17 prospective studies.

The health effects of omega-3 fatty acids have been controversial. Here we report the results of a de novo pooled analysis conducted with data from 17 prospective cohort studies examining the associations between blood omega-3 fatty acid levels and risk for all-cause mortality. Over a median of 16 years of follow-up, 15,720 deaths occurred among 42,466 individuals. We found that, after multivariable adjustment for relevant risk factors, risk for death from all causes was significantly lower (by 15-18%, at least p < 0.003) in the highest vs the lowest quintile for circulating long chain (20-22 carbon) omega-3 fatty acids (eicosapentaenoic, docosapentaenoic, and docosahexaenoic acids). Similar relationships were seen for death from cardiovascular disease, cancer and other causes. No associations were seen with the 18-carbon omega-3, alpha-linolenic acid. These findings suggest that higher circulating levels of marine n-3 PUFA are associated with a lower risk of premature death.

Urinary Phthalate Biomarkers and Bone Mineral Density in Postmenopausal Women.

CONTEXT: Phthalates are endocrine-disrupting chemicals that could disrupt normal physiologic function, triggering detrimental impacts on bone. OBJECTIVE: We evaluated associations between urinary phthalate biomarkers and BMD in postmenopausal women participating in the prospective Women's Health Initiative (WHI). METHODS: We included WHI participants enrolled in the BMD substudy and selected for a nested case-control study of phthalates and breast cancer (N = 1255). We measured 13 phthalate biomarkers and creatinine in 2 to 3 urine samples per participant collected over 3 years, when all participants were cancer free. Total hip and femoral neck BMD were measured at baseline and year 3, concurrent with urine collection, via dual-energy x-ray absorptiometry. We fit multivariable generalized estimating equation models and linear mixed-effects models to estimate cross-sectional and longitudinal associations, respectively, with stratification on postmenopausal hormone therapy (HT) use. RESULTS: In cross-sectional analyses, mono-3-carboxypropyl phthalate and the sum of di-isobutyl phthalate metabolites were inversely associated with total hip BMD among HT nonusers, but not among HT users. Longitudinal analyses showed greater declines in total hip BMD among HT nonusers and with highest concentrations of mono-3-carboxyoctyl phthalate (-1.80%; 95% CI, -2.81% to -0.78%) or monocarboxynonyl phthalate (-1.84%; 95% CI, -2.80% to -0.89%); similar associations were observed with femoral neck BMD. Among HT users, phthalate biomarkers were not associated with total hip or femoral neck BMD change. CONCLUSION: Certain phthalate biomarkers are associated with greater percentage decreases in total hip and femoral neck BMD. These findings suggest that phthalate exposure may have clinically important effects on BMD, and potentially fracture risk.

A randomized controlled trial of methylergonovine prophylaxis after dilation and evacuation abortion.

OBJECTIVE: To evaluate the efficacy of intramuscular methylergonovine maleate as prophylaxis against excessive bleeding when given after dilation and evacuation (D&E) at 20-24 weeks. STUDY DESIGN: We performed a randomized, double-blinded, placebo-controlled trial in patients without excessive bleeding requiring intervention after D&E completion. We administered study treatment within one minute of the end of the procedure. We primarily compared outcomes using a composite of indicators of excessive post-procedure blood loss (post-procedure measured blood loss exceeding 125 mL, uterine massage or compression for at least two minutes, administration of additional uterotonic medication, intrauterine balloon tamponade, uterine re-aspiration, blood transfusion, uterine artery embolization, hospital admission for bleeding, or major surgery). Secondary outcomes included individual indicator occurrences, satisfaction, and side effects. RESULTS: From March 3, 2015 to March 31, 2017, we randomized 284 participants (n = 140 methylergonovine, n = 144 placebo), five before we registered the trial with clinicaltrials.gov. Baseline characteristics were similar between groups. The composite outcome occurred in 78 (56%) methylergonovine and 75 (52%) placebo participants (p = 0.5). Methylergonovine recipients required more intrauterine balloon use (n = 20 [14%]) versus placebo (n = 10 [7%]), p = 0.04. We also observed a non-significant trend towards more uterotonic administration (n = 56 [40%] versus n = 43 [30%], p = 0.07) and hospital admissions for bleeding (n = 4 [3%] versus n = 0, p = 0.06) in the methylergonovine group compared to placebo. CONCLUSION: We observed no improvement in the composite outcome for excessive bleeding with prophylactic post-procedure methylergonovine. In addition, individual excessive bleeding outcomes occurred more frequently in the methylergonovine group, potentially indicating harm with its prophylactic use after D&E. IMPLICATIONS: When administered prophylactically immediately after dilation and evacuation abortion at 20-24 weeks, methylergonovine increases uterine bleeding. Given the lack of data for effectiveness as a prophylactic agent and our findings indicating harm, we do not recommend its use for post-operative prophylaxis.

Into the wild and on to the table: A Western Trauma Association multicenter analysis and comparison of wilderness falls in rock climbers and nonclimbers.

BACKGROUND: Wilderness activities expose outdoor enthusiasts to austere environments with injury potential, including falls from height. The majority of published data on falls while climbing or hiking are from emergency departments. We sought to more accurately describe the injury pattern of wilderness falls that lead to serious injury requiring trauma center evaluation and to further distinguish climbing as a unique pattern of injury. METHODS: Data were collected from 17 centers in 11 states on all wilderness falls (fall from cliff: International Classification of Diseases, Ninth Revision, e884.1; International Classification of Diseases, 10th Revision, w15.xx) from 2006 to 2018 as a Western Trauma Association multicenter investigation. Demographics, injury characteristics, and care delivery were analyzed. Comparative analyses were performed for climbing versus nonclimbing mechanisms. RESULTS: Over the 13-year study period, 1,176 wilderness fall victims were analyzed (301 climbers, 875 nonclimbers). Fall victims were male (76%), young (33 years), and moderately injured (Injury Severity Score, 12.8). Average fall height was 48 ft, and average rescue/transport time was 4 hours. Nineteen percent were intoxicated. The most common injury regions were soft tissue (57%), lower extremity (47%), head (40%), and spine (36%). Nonclimbers had a higher incidence of severe head and facial injuries despite having equivalent overall Injury Severity Score. On multivariate analysis, climbing remained independently associated with increased need for surgery but lower odds of composite intensive care unit admission/death. Contrary to studies of urban falls, height of fall in wilderness falls was not independently associated with mortality or Injury Severity Score. CONCLUSION: Wilderness falls represent a unique population with distinct patterns of predominantly soft tissue, head, and lower extremity injury. Climbers are younger, usually male, more often discharged home, and require more surgery but less critical care. LEVEL OF EVIDENCE: Epidemiological, Level IV.

Cardiovascular Outcomes in Relation to Antihypertensive Medication Use in Women with and Without Cancer: Results from the Women's Health Initiative.

BACKGROUND: Recent clinical trials have evaluated angiotensin-converting enzyme (ACE) inhibitors (ACEis), angiotensin receptor blockers (ARBs), and beta blockers (BBs) in relation to cardiotoxicity in patients with cancer, typically defined by ejection fraction declines. However, these trials have not examined long-term, hard clinical endpoints. Within a prospective study, we examined the risk of heart failure (HF) and coronary heart disease (CHD) events in relation to use of commonly used antihypertensive medications, including ACEis/ARBs, BBs, calcium channel blockers (CCB), and diuretics, comparing women with and without cancer. MATERIALS AND METHODS: In a cohort of 56,997 Women's Health Initiative study participants free of cardiovascular disease who received antihypertensive treatment, we used multivariable-adjusted Cox regression models to calculate the hazard ratios (HRs) of developing CHD, HF, and a composite outcome of cardiac events (combining CHD and HF) in relation to use of ACEis/ARBs, CCBs, or diuretics versus BBs, separately in women with and without cancer. RESULTS: Whereas there was no difference in risk of cardiac events comparing ACEi/ARB with BB use among cancer-free women (HR = 0.99 [0.88-1.12]), among cancer survivors ACEi/ARB users were at a 2.24-fold risk of total cardiac events (1.18-4.24); p-interaction = .06). When investigated in relation to CHD only, an increased risk was similarly observed in ACEi/ARB versus BB use for cancer survivors (HR = 1.87 [0.88-3.95]) but not in cancer-free women (HR = 0.91 [0.79-1.06]; p-interaction = .04). A similar pattern was also seen in relation to HF but did not reach statistical significance (p-interaction = .23). CONCLUSION: These results from this observational study suggest differing risks of cardiac events in relation to antihypertensive medications depending on history of cancer. Although these results require replication before becoming actionable in a clinical setting, they suggest the need for more rigorous examination of the effect of antihypertensive choice on long-term cardiac outcomes in cancer survivors. IMPLICATIONS FOR PRACTICE: Although additional research is needed to replicate these findings, these data from a large, nationally representative sample of postmenopausal women indicate that beta blockers are favorable to angiotensin-converting enzyme inhibitors in reducing the risk of cardiac events among cancer survivors. This differs from the patterns observed in a noncancer cohort, which largely mirrors what is found in the randomized clinical trials in the general population.

Altered gait mechanics are associated with severity of chondropathy after hip arthroscopy for femoroacetabular impingement syndrome.

BACKGROUND: Suboptimal patient-reported function and movement impairments often persist after hip arthroscopy for femoroacetabular impingement syndrome (FAIS). Individuals with FAIS with preoperative cartilage pathology (ie. chondropathy) demonstrate distinct movement patterns and have worse post-operative outcomes. It is unknown whether the presence of chondropathy after surgery negatively affects movement and function. RESEARCH QUESTION: Do sagittal plane gait mechanics differ based on chondropathy severity following arthroscopy for FAIS? METHODS: A cross-sectional walking gait analysis was performed for 25 participants post-arthroscopy (2.48 ±â€¯1.38y) and 12 healthy controls (HCs). Peak total support moment (TSM) and relative contributions of the hip, knee, and ankle were calculated during loading response. The Hip Osteoarthritis MRI Scoring System was used to categorize the FAIS group into no-mild or moderate-severe chondropathy groups based on 3 T magnetic resonance imaging of their surgical hip. The interactions of group by limb were evaluated for kinetic variables, covaried by gait speed. RESULTS: Groups did not differ based on age, BMI and sex distribution (P ≥ 0.14). 13 participants with FAIS presented with moderate-severe chondropathy and 12 presented with no-mild chondropathy. Participants with moderate-severe chondropathy walked significantly slower than both other groups (P = 0.006) and demonstrated lower peak TSM than those with no-mild chondropathy (P = 0.002). Participants with no-mild chondropathy demonstrated lower hip (61.5 %) and greater ankle (17.7 %) contributions to the TSM on the involved limb compared to the moderate-severe group (hip:73.4 %, P = 0.07; ankle:10.5 %, P = 0.007). SIGNIFICANCE: Slower gait speed alone did not explain the lower TSM strategy in participants with moderate-severe chondropathy. Interestingly, the joint contribution strategy of this group was not different than HCs. Participants with no-mild chondropathy demonstrated a TSM strategy that shifted the demand away from their hip and toward their ankle. Given the small sample size, and large variability in joint strategies, future work needs to examine whether these alterations in gait strategy, with or without advanced chondropathy, impact patient function.

History of etidronate.

Etidronate is a non-nitrogen-containing bisphosphonate. Because it binds with calcium and inhibits crystal formation and dissolution, it was considered by Procter & Gamble as an additive to toothpaste (to prevent build-up of tartar) and detergent (to bind calcium and increase sudsing in "hard" water). The first clinical use (1968) was for fibrodysplasia ossificans progressiva. The first approved clinical use (1977) was for treatment of Paget's disease of bone. Other approved indications are hypercalcemia of malignancy and heterotopic ossification, with a host of off-label uses (including fibrous dysplasia, periodontal disease, multiple myeloma, neuropathic arthropathy, pulmonary microlithiasis, diabetic retinopathy, bone metastases, melorheostosis, urinary stone disease, periodontal disease, etc.). Unique among bisphosphonates, etidronate (oral therapy) results in hyperphosphatemia, increased tubular reabsorption of phosphorus and increased levels of 1,25-dihydroxyvitamin D. The dose that reduces bone resorption is close to the dose that impairs mineralization; prolonged high-dose use can result in osteomalacia and bone fractures. Intermittent cyclic etidronate for osteoporosis resulted in favorable changes in bone density and histomorphometry (no mineralization defect) as well as a decrease in vertebral fracture rates in postmenopausal women with osteoporosis. Later studies showed similar effects in men with osteoporosis and patients with glucocorticoid-induced osteoporosis. Although its use for osteoporosis has given way to newer bisphosphonates and other agents, because of its unique properties, it remains the bisphosphonate of choice for treatment of heterotopic ossification.

ENDS Flavor Preference by Menthol Cigarette Smoking Status among US Adults, 2018-2019.

E-cigarette flavor preference may differ among smokers using e-cigarettes, but little information is available on preferences by menthol cigarette status. Using nationally representative data for US adults from the 2018-2019 Tobacco Use Supplement to the Current Population Survey, we analyzed e-cigarette flavor preference by menthol cigarette status and e-cigarette device type for dual-cigarette and e-cigarette users and e-cigarette users who had recently quit smoking by trying to switch to e-cigarettes ("switchers"). Approximately half (52.2%) of dual users of menthol cigarettes and e-cigarettes reported using menthol/mint-flavored e-cigarettes as did 41.4% of "switchers" who had smoked menthol cigarettes; exclusive menthol/mint flavor use was 13.1% for dual users and 21.3% for "switchers." A similar proportion (45.1%) of dual users who smoked nonmenthol cigarettes used tobacco-flavored e-cigarettes, but only 26.7% of "switchers" who had smoked nonmenthol cigarettes used tobacco-flavored e-cigarettes. Approximately 60% of dual users and "switchers" used fruit/other flavors, regardless of menthol cigarette use. By device type, 63.9% of dual users of cartridge-based e-cigarettes and menthol cigarettes used menthol/mint-flavored e-cigarettes. Approximately 75% of dual users and 85% of "switchers" who used tank or mod systems used fruit/other flavors. Menthol cigarette smokers may be particularly likely to use menthol/mint e-cigarettes, and a majority of dual users and "switchers" used fruit/other flavors. These results can inform policy measures concerning flavored electronic nicotine delivery system products.

Inherited variants at 3q13.33 and 3p24.1 are associated with risk of diffuse large B-cell lymphoma and implicate immune pathways.

We previously identified five single nucleotide polymorphisms (SNPs) at four susceptibility loci for diffuse large B-cell lymphoma (DLBCL) in individuals of European ancestry through a large genome-wide association study (GWAS). To further elucidate genetic susceptibility to DLBCL, we sought to validate two loci at 3q13.33 and 3p24.1 that were suggestive in the original GWAS with additional genotyping. In the meta-analysis (5662 cases and 9237 controls) of the four original GWAS discovery scans and three replication studies, the 3q13.33 locus (rs9831894; minor allele frequency [MAF] = 0.40) was associated with DLBCL risk [odds ratio (OR) = 0.83, P = 3.62 × 10-13]. rs9831894 is in linkage disequilibrium (LD) with additional variants that are part of a super-enhancer that physically interacts with promoters of CD86 and ILDR1. In the meta-analysis (5510 cases and 12 817 controls) of the four GWAS discovery scans and four replication studies, the 3p24.1 locus (rs6773363; MAF = 0.45) was also associated with DLBCL risk (OR = 1.20, P = 2.31 × 10-12). This SNP is 29 426-bp upstream of the nearest gene EOMES and in LD with additional SNPs that are part of a highly lineage-specific and tumor-acquired super-enhancer that shows long-range interaction with AZI2 promoter. These loci provide additional evidence for the role of immune function in the etiology of DLBCL, the most common lymphoma subtype.