The effect of change in body mass index on volumetric measures of mammographic density.

Understanding how changes in body mass index (BMI) relate to changes in mammographic density is necessary to evaluate adjustment for BMI gain/loss in studies of change in density and breast cancer risk. Increase in BMI has been associated with a decrease in percent density, but the effect on change in absolute dense area or volume is unclear. We examined the association between change in BMI and change in volumetric breast density among 24,556 women in the San Francisco Mammography Registry from 2007 to 2013. Height and weight were self-reported at the time of mammography. Breast density was assessed using single x-ray absorptiometry measurements. Cross-sectional and longitudinal associations between BMI and dense volume (DV), non-dense volume (NDV), and percent dense volume (PDV) were assessed using multivariable linear regression models, adjusted for demographics, risk factors, and reproductive history. In cross-sectional analysis, BMI was positively associated with DV [β, 2.95 cm(3); 95% confidence interval (CI), 2.69-3.21] and inversely associated with PDV (β, -2.03%; 95% CI, -2.09, -1.98). In contrast, increasing BMI was longitudinally associated with a decrease in both DV (β, -1.01 cm(3); 95% CI, -1.59, -0.42) and PDV (β, -1.17%; 95% CI, -1.31, -1.04). These findings were consistent for both pre- and postmenopausal women. Our findings support an inverse association between change in BMI and change in PDV. The association between increasing BMI and decreasing DV requires confirmation. Longitudinal studies of PDV and breast cancer risk, or those using PDV as an indicator of breast cancer risk, should evaluate adjustment for change in BMI.

Hart V ，Reeves KW ，Sturgeon SR ，Reich NG ，Sievert LL ，Kerlikowske K ，Ma L ，Shepherd J ，Tice JA ，Mahmoudzadeh AP ，Malkov S ，Sprague BL ... -  《-》

Reproductive factors and mammographic density within the International Consortium of Mammographic Density: A cross-sectional study.

Elevated mammographic density (MD) for a woman's age and body mass index (BMI) is an established breast cancer risk factor. The relationship of parity, age at first birth, and breastfeeding with MD is less clear. We examined the associations of these factors with MD within the International Consortium of Mammographic Density (ICMD). ICMD is a consortium of 27 studies with pooled individual-level epidemiological and MD data from 11,755 women without breast cancer aged 35-85 years from 22 countries, capturing 40 country-& ethnicity-specific population groups. MD was measured using the area-based tool Cumulus. Meta-analyses across population groups and pooled analyses were used to examine linear regression associations of square-root (√) transformed MD measures (percent MD (PMD), dense area (DA), and non-dense area (NDA)) with parity, age at first birth, ever/never breastfed and lifetime breastfeeding duration. Models were adjusted for age at mammogram, age at menarche, BMI, menopausal status, use of hormone replacement therapy, calibration method, mammogram view and reader, and parity and age at first birth when not the association of interest. Among 10,988 women included in these analyses, 90.1% (n = 9,895) were parous, of whom 13% (n = 1,286) had ≥ five births. The mean age at first birth was 24.3 years (Standard deviation = 5.1). Increasing parity (per birth) was inversely associated with √PMD (β: - 0.05, 95% confidence interval (CI): - 0.07, - 0.03) and √DA (β: - 0.08, 95% CI: - 0.12, - 0.05) with this trend evident until at least nine births. Women who were older at first birth (per five-year increase) had higher √PMD (β:0.06, 95% CI:0.03, 0.10) and √DA (β:0.06, 95% CI:0.02, 0.10), and lower √NDA (β: - 0.06, 95% CI: - 0.11, - 0.01). In stratified analyses, this association was only evident in women who were post-menopausal at MD assessment. Among parous women, no associations were found between ever/never breastfed or lifetime breastfeeding duration (per six-month increase) and √MD. Associations with higher parity and older age at first birth with √MD were consistent with the direction of their respective associations with breast cancer risk. Further research is needed to understand reproductive factor-related differences in the composition of breast tissue and their associations with breast cancer risk.

O'Driscoll J ，Burton A ，Maskarinec G ，Perez-Gomez B ，Vachon C ，Miao H ，Lajous M ，López-Ridaura R ，Eliassen AH ，Pereira A ，Garmendia ML ，Tamimi RM ，Bertrand K ，Kwong A ，Ursin G ，Lee E ，Qureshi SA ，Ma H ，Vinnicombe S ，Moss S ，Allen S ，Ndumia R ，Vinayak S ，Teo SH ，Mariapun S ，Fadzli F ，Peplonska B ，Nagata C ，Stone J ，Hopper JL ，Giles G ，Ozmen V ，Aribal ME ，Schüz J ，Van Gils CH ，Wanders JOP ，Sirous R ，Sirous M ，Hipwell J ，Kim J ，Lee JW ，Hartman M ，Li J ，Scott C ，Chiarelli AM ，Linton L ，Pollan M ，Flugelman AA ，Salem D ，Kamal R ，Boyd N ，Dos-Santos-Silva I ，McCormack V ，Mullooly M ... -  《-》

Comparison of Two Modern Survival Prediction Tools, SORG-MLA and METSSS, in Patients With Symptomatic Long-bone Metastases Who Underwent Local Treatment With Surgery Followed by Radiotherapy and With Radiotherapy Alone.

Survival estimation for patients with symptomatic skeletal metastases ideally should be made before a type of local treatment has already been determined. Currently available survival prediction tools, however, were generated using data from patients treated either operatively or with local radiation alone, raising concerns about whether they would generalize well to all patients presenting for assessment. The Skeletal Oncology Research Group machine-learning algorithm (SORG-MLA), trained with institution-based data of surgically treated patients, and the Metastases location, Elderly, Tumor primary, Sex, Sickness/comorbidity, and Site of radiotherapy model (METSSS), trained with registry-based data of patients treated with radiotherapy alone, are two of the most recently developed survival prediction models, but they have not been tested on patients whose local treatment strategy is not yet decided. (1) Which of these two survival prediction models performed better in a mixed cohort made up both of patients who received local treatment with surgery followed by radiotherapy and who had radiation alone for symptomatic bone metastases? (2) Which model performed better among patients whose local treatment consisted of only palliative radiotherapy? (3) Are laboratory values used by SORG-MLA, which are not included in METSSS, independently associated with survival after controlling for predictions made by METSSS? Between 2010 and 2018, we provided local treatment for 2113 adult patients with skeletal metastases in the extremities at an urban tertiary referral academic medical center using one of two strategies: (1) surgery followed by postoperative radiotherapy or (2) palliative radiotherapy alone. Every patient's survivorship status was ascertained either by their medical records or the national death registry from the Taiwanese National Health Insurance Administration. After applying a priori designated exclusion criteria, 91% (1920) were analyzed here. Among them, 48% (920) of the patients were female, and the median (IQR) age was 62 years (53 to 70 years). Lung was the most common primary tumor site (41% [782]), and 59% (1128) of patients had other skeletal metastases in addition to the treated lesion(s). In general, the indications for surgery were the presence of a complete pathologic fracture or an impending pathologic fracture, defined as having a Mirels score of ≥ 9, in patients with an American Society of Anesthesiologists (ASA) classification of less than or equal to IV and who were considered fit for surgery. The indications for radiotherapy were relief of pain, local tumor control, prevention of skeletal-related events, and any combination of the above. In all, 84% (1610) of the patients received palliative radiotherapy alone as local treatment for the target lesion(s), and 16% (310) underwent surgery followed by postoperative radiotherapy. Neither METSSS nor SORG-MLA was used at the point of care to aid clinical decision-making during the treatment period. Survival was retrospectively estimated by these two models to test their potential for providing survival probabilities. We first compared SORG to METSSS in the entire population. Then, we repeated the comparison in patients who received local treatment with palliative radiation alone. We assessed model performance by area under the receiver operating characteristic curve (AUROC), calibration analysis, Brier score, and decision curve analysis (DCA). The AUROC measures discrimination, which is the ability to distinguish patients with the event of interest (such as death at a particular time point) from those without. AUROC typically ranges from 0.5 to 1.0, with 0.5 indicating random guessing and 1.0 a perfect prediction, and in general, an AUROC of ≥ 0.7 indicates adequate discrimination for clinical use. Calibration refers to the agreement between the predicted outcomes (in this case, survival probabilities) and the actual outcomes, with a perfect calibration curve having an intercept of 0 and a slope of 1. A positive intercept indicates that the actual survival is generally underestimated by the prediction model, and a negative intercept suggests the opposite (overestimation). When comparing models, an intercept closer to 0 typically indicates better calibration. Calibration can also be summarized as log(O:E), the logarithm scale of the ratio of observed (O) to expected (E) survivors. A log(O:E) > 0 signals an underestimation (the observed survival is greater than the predicted survival); and a log(O:E) < 0 indicates the opposite (the observed survival is lower than the predicted survival). A model with a log(O:E) closer to 0 is generally considered better calibrated. The Brier score is the mean squared difference between the model predictions and the observed outcomes, and it ranges from 0 (best prediction) to 1 (worst prediction). The Brier score captures both discrimination and calibration, and it is considered a measure of overall model performance. In Brier score analysis, the "null model" assigns a predicted probability equal to the prevalence of the outcome and represents a model that adds no new information. A prediction model should achieve a Brier score at least lower than the null-model Brier score to be considered as useful. The DCA was developed as a method to determine whether using a model to inform treatment decisions would do more good than harm. It plots the net benefit of making decisions based on the model's predictions across all possible risk thresholds (or cost-to-benefit ratios) in relation to the two default strategies of treating all or no patients. The care provider can decide on an acceptable risk threshold for the proposed treatment in an individual and assess the corresponding net benefit to determine whether consulting with the model is superior to adopting the default strategies. Finally, we examined whether laboratory data, which were not included in the METSSS model, would have been independently associated with survival after controlling for the METSSS model's predictions by using the multivariable logistic and Cox proportional hazards regression analyses. Between the two models, only SORG-MLA achieved adequate discrimination (an AUROC of > 0.7) in the entire cohort (of patients treated operatively or with radiation alone) and in the subgroup of patients treated with palliative radiotherapy alone. SORG-MLA outperformed METSSS by a wide margin on discrimination, calibration, and Brier score analyses in not only the entire cohort but also the subgroup of patients whose local treatment consisted of radiotherapy alone. In both the entire cohort and the subgroup, DCA demonstrated that SORG-MLA provided more net benefit compared with the two default strategies (of treating all or no patients) and compared with METSSS when risk thresholds ranged from 0.2 to 0.9 at both 90 days and 1 year, indicating that using SORG-MLA as a decision-making aid was beneficial when a patient's individualized risk threshold for opting for treatment was 0.2 to 0.9. Higher albumin, lower alkaline phosphatase, lower calcium, higher hemoglobin, lower international normalized ratio, higher lymphocytes, lower neutrophils, lower neutrophil-to-lymphocyte ratio, lower platelet-to-lymphocyte ratio, higher sodium, and lower white blood cells were independently associated with better 1-year and overall survival after adjusting for the predictions made by METSSS. Based on these discoveries, clinicians might choose to consult SORG-MLA instead of METSSS for survival estimation in patients with long-bone metastases presenting for evaluation of local treatment. Basing a treatment decision on the predictions of SORG-MLA could be beneficial when a patient's individualized risk threshold for opting to undergo a particular treatment strategy ranged from 0.2 to 0.9. Future studies might investigate relevant laboratory items when constructing or refining a survival estimation model because these data demonstrated prognostic value independent of the predictions of the METSSS model, and future studies might also seek to keep these models up to date using data from diverse, contemporary patients undergoing both modern operative and nonoperative treatments. Level III, diagnostic study.

Lee CC ，Chen CW ，Yen HK ，Lin YP ，Lai CY ，Wang JL ，Groot OQ ，Janssen SJ ，Schwab JH ，Hsu FM ，Lin WH ... -  《-》

Defining the optimum strategy for identifying adults and children with coeliac disease: systematic review and economic modelling.

Elwenspoek MM ，Thom H ，Sheppard AL ，Keeney E ，O'Donnell R ，Jackson J ，Roadevin C ，Dawson S ，Lane D ，Stubbs J ，Everitt H ，Watson JC ，Hay AD ，Gillett P ，Robins G ，Jones HE ，Mallett S ，Whiting PF ... -  《-》

How Does Shame Relate to Clinical and Psychosocial Outcomes in Knee Osteoarthritis?

Knee osteoarthritis (OA) is a common and disabling condition that often carries severe psychosocial implications. Chronic illness-related shame has emerged as a substantial psychosocial factor affecting individuals with knee OA, but it is unclear how chronic illness-related shame is associated with the long-term clinical and psychosocial outcomes in individuals with knee OA. (1) Does a higher level of shame correlate with worse clinical and psychosocial outcomes at baseline among individuals with knee OA? (2) Is a higher level of shame at baseline associated with worse clinical and psychosocial outcomes at 4-month and 12-month follow-up among individuals with knee OA? (3) Are sociodemographic characteristics correlated with levels of shame among individuals with knee OA? Between June 2021 and February 2022, we screened 977 patients based on the inclusion criteria of (1) age 45 years or older, (2) independent in community mobility with or without walking aids, (3) proficient in English or Chinese language, and (4) met the clinical criteria for OA diagnosis outlined by the National Institute for Health and Care Excellence. Of these patients, 47% (460) were eligible and enrolled. A further 53% (517) were excluded for prespecified reasons. Of the 460 enrolled patients, 7% (30) dropped out before data collection began, and 46% (210) of patients did not complete the psychological questionnaires, leaving 48% (220) of patients for analysis. From this final sample, 25% (56) were lost to follow-up at 4 months, and an additional 7% (16) were lost by the 12-month follow-up, leaving 67% (148) of the original eligible group for analysis. All patients were recruited from the outpatient clinics of the orthopaedic and physiotherapy departments across two Singapore hospitals within the National Healthcare Group. The study population had a mean ± SD age of 64 ± 8 years, with 69% (152 of 220) women, and the mean ± SD duration of knee OA symptoms was 6 ± 6 years. Outcome measures used were the Chronic Illness-Related Shame Scale (CISS), the 12-item Knee Injury and Osteoarthritis Outcome Score (KOOS-12), Patient Health Questionnaire 4 (PHQ-4), the 8-item Arthritis Self-Efficacy Scale (ASES-8), and the Brief Fear of Movement Scale (BFOM). The CISS is a validated tool specifically designed to measure feelings of shame (internal and external shame) in individuals living with chronic illness. The scale has been validated for use among patients with knee OA in Singapore. The functional outcome measure used was the Modified Barthel Index. Data on demographic characteristics were collected. Data were collected at baseline, 4-month follow-up, and 12-month follow-up. Statistical analyses included the Spearman correlation, linear regression, and cluster analysis. At baseline, there was a weak to moderate negative correlation between CISS scores and KOOS-12 and ASES-8 scores (Spearman correlation coefficients ranged from -0.46 to -0.36; all p values < 0.001), indicating that higher levels of shame were associated with slightly to moderately worse knee function and lower self-efficacy. There was a modest positive correlation between CISS scores and PHQ-4 and BFOM scores (the Spearman correlation coefficients ranged from 0.43 to 0.46; all p values < 0.001), indicating that higher levels of shame were linked to more psychological distress and greater fear of movement. At the 4-month follow-up, a higher CISS score at baseline was associated with a decrease in KOOS-12 (adjusted coefficient -0.86 [95% confidence interval (CI) -1.33 to -0.40]; p < 0.001) and ASES-8 (adjusted coefficient -0.12 [95% CI -0.19 to -0.06]; p < 0.001) scores, indicating worsened knee function and reduced self-efficacy over time. Higher CISS scores at baseline were also associated with an increase in PHQ-4 (adjusted coefficient 0.23 [95% CI 0.14 to 0.31]; p < 0.001) and BFOM (adjusted coefficient 0.22 [95% CI 0.08 to 0.36]; p = 0.002) scores at the 4-month follow-up, reflecting greater psychological distress and greater fear of movement. At the 12-month follow-up, a higher CISS score at baseline was associated with a decrease in KOOS-12 (adjusted coefficient -0.72 [95% CI -1.25 to -0.19]; p = 0.008) and ASES-8 (adjusted coefficient -0.12 [95% CI -0.20 to -0.04]; p = 0.002) scores, indicating that those with higher initial levels of shame continued to experience poorer knee function and lower self-efficacy. Higher CISS scores at baseline were also associated with an increase in PHQ-4 (adjusted coefficient 0.13 [95% CI 0.04 to 0.21]; p = 0.004) as well as BFOM (adjusted coefficient 0.20 [95% CI 0.06 to 0.34]; p = 0.007) scores at the 12-month follow-up, indicating ongoing psychological distress and fear of movement. Cluster analysis found that unemployed older patients with lower CISS scores and BMI, as well as having unilateral arthritis and shorter duration of OA, were observed to have better knee function at 4 months (mean difference 7 [95% CI 1 to 12]; p = 0.02) and 12 months (mean difference 7 [95% CI 1 to 13]; p = 0.02) compared with the opposite. After controlling for age, gender, ethnicity, and employment status, the regression analysis found that higher BMI was related to higher CISS scores (adjusted coefficient 0.21 [95% CI 0.07 to 0.34]; p = 0.003). Chronic illness-related shame has a small to modest association with clinical and psychosocial outcomes for individuals with knee OA. Healthcare professionals should routinely incorporate psychosocial assessments to identify and manage shame early, potentially improving both clinical and psychosocial outcomes. Recognizing that higher BMI is linked to increased shame can specifically guide targeted emotional and psychosocial support. Additionally, integrating interventions such as acceptance and commitment therapy and peer support with traditional treatments could enhance adherence and overall patient outcomes, making comprehensive care more effective. Level II, prognostic study.

Yeo JY ，Lim CJ ，Yang SY ，Tan BY ... -  《-》